Inhibitory effect of d-allose on neutrophil activation after rat renal ischemia/reperfusion

D-Allose is one of the rare sugars produced from D-psicose. We examined whether d-allose reduces the extent of rat renal ischemia/reperfusion (I/R) injury by suppressing the activation of neutrophils. The renal concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1 and myeloperoxidase were significantly increased after renal I/R. These increases were significantly inhibited by D-allose administration. Furthermore, D-allose significantly inhibited the increase in the concentrations of blood urea nitrogen (BUN), creatinine, N-acetyl beta-D-glucosaminidase (NAG) and histopathologic changes after renal I/R. These findings strongly suggest that D-allose protects against I/R-induced renal injury by inhibiting the activation of neutrophils that play an important role in I/R-induced renal injury. These findings may have important implications in understanding the biologic functions of D-allose. D-Allose may prove useful in renal surgery and transplantation.     

Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats

Recovery from ischemic acute kidney injury requires the replacement of damaged tubular cells. This repair process involves epidermal growth factor (EGF) synthesized in medullary the thick ascending limbs (mTAL) of Henle. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, increases glomerular filtration rate and renal medullary blood flow. However, the effects of ANP on renal recovery after I/R-induced renal injury remain unclear. We therefore examined whether human ANP enhances recovery from I/R-induced renal injury by reducing damage to EGF-producing kidney cells in a rat model. Male Wistar rats weighing 200–240 g were observed for 48 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered α-human ANP (α-hANP) at 0.2 μg/kg/min beginning immediately after ischemia and continuing for 2 h after reperfusion. Outer medullary blood flow (OMBF), EGF mRNA, serum blood urea nitrogen (BUN) and creatinine levels as indicators of glomerular function were measured, while urinary N-acetyl β-d-glucosaminidase (NAG) was used as a specific indicator of proximal tubular function. OMBF was increased by α-hANP after reperfusion and maintained significantly higher mRNA level of EGF in the kidney 24 h after reperfusion. I/R-induced increases in serum concentrations of BUN and creatinine and urinary concentrations of NAG were also reduced by α-hANP, with improved histopathological changes, including acute tubular necrosis at 24–48 h after reperfusion. This report is the first to demonstrate that α-hANP accelerates recovery following renal ischemic insult by reducing the damage to EGF-producing kidney cells.     

D-allose protects against endotoxemic acute renal injury

D-allose is a monosaccharide. We previously reported that D-allose attenuated renal injury by inhibiting the activation of neutrophils after renal ischemia/reperfusion. Lipopolysaccharide (LPS) triggers sepsis syndrome by activating monocytes to produce proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, which potently stimulates the activation of neutrophils. This study was undertaken to examine the effects of D-allose on renal injury in the systemic inflammatory response induced by LPS administration, with emphasis on systemic TNF-alpha and the activation of neutrophils in the rat kidney. Serum and renal TNF-alpha, renal cytokine-induced neutrophil chemoattractant (CINC)-1, and myeloperoxidase (MPO) concentrations, and renal function after LPS administration were evaluated. D-allose (400 mg/kg body weight) inhibited LPS-induced increases in serum and renal TNF-alpha concentrations and renal CINC-1 and MPO concentrations after LPS administration, as well as the subsequent neutrophil-mediated renal injury. These findings may have important implications in understanding the biologic functions of D-allose. D-allose may prove useful in protecting against acute renal injury in systemic inflammatory responses to LPS.     

Urinary trypsin inhibitor reduces inflammatory response in kidney induced by lipopolysaccharide

Human urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used in Japan as a drug for patients with acute inflammatory disorders such as septic shock and pancreatitis. Lipopolysaccharide (LPS) triggers the sepsis syndrome by activating monocytes to produce proinflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), which potently stimulate the activation of neutrophils. The inhibitory mechanism of UTI on the systemic inflammatory response induced by the intraperitoneal injection of LPS in the kidney is unclear. This study was undertaken to examine the inhibitory effects of UTI on renal injury associated with the systemic inflammatory response induced by LPS stimulation, with emphasis on systemic TNFalpha and the activation of neutrophils in rat kidney. The systemic inflammatory response syndrome was induced by LPS treatment. Serum and renal TNFalpha, renal cytokine-induced neutrophil chemoattractant-1 (CINC-1) and myeloperoxidase (MPO) levels, as well as renal function after LPS stimulation, were evaluated. UTI (50,000 U/kg) inhibited LPS-induced increases in the serum and renal tissue levels of TNFalpha, as well as the renal tissue levels of CINC-1 and MPO after LPS stimulation. UTI (50,000 U/kg) also inhibited the production of serum TNFalpha associated with the systemic inflammatory response syndrome induced by LPS stimulation, thereby attenuating neutrophil infiltration into renal tissues and subsequent neutrophil-mediated renal injury. These findings may have important implications in understanding the biologic functions of UTI. UTI may prove useful in protecting against acute renal injury associated with a systemic inflammatory response.     

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity,Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia–reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.     

北五味子乙素对大鼠离体心肌缺血再灌注损伤的保护作用及分子机制

目的：观察北五味子乙素（schisandrin B,SchB）对缺血再灌注（ischemia/reperfusion,I/R）大鼠离体心脏功能、梗死面积、乳酸脱氢酶及相关蛋白表达的影响,探讨其对I/R损伤的保护作用及分子机制。方法：Wistar大鼠50 只,随机分为5 组：空白对照组（CON）、缺血再灌注组（I/R）、SchB预保护组（SchB）、PI3K抑制剂组（I/R＋SchB＋LY）、腺苷酸活化的蛋白激酶（AMP-activated protein kinase,AMPK）抑制剂组（I/R＋SchB＋CC）。采用Langendorff法建立离体大鼠心脏I/R模型,心肌缺血2 h,再灌注5、15、30、60 min。观察I/R期间室内压最大上升速率（＋dp/dtmax）、室内压最大下降速率（－dp/dtmax）、左心室舒张末压、冠脉流量和心率;测定心脏灌流液中乳酸脱氢酶（lactate dehydrogenase,LDH）含量,2,3,5-氯化三苯基四氮唑（2,3,5-triphenyltertrazoliumchloride,TTC）染色测定各组心肌梗死面积;免疫印迹检测心肌中总蛋白激酶B（protein kinase B,PKB）、磷酸化Akt（p-Akt）、总糖原合成酶激酶-3β（glycogen synthease kinase-3β,GSK-3β）、磷酸化GSK-3β（p-GSK-3β）蛋白表达。结果：SchB可显著改善I/R所致的心肌功能损伤,减少梗死面积,提高心肌中p-Akt和p-GSK-3β蛋白表达。结论：SchB对大鼠离体心脏I/R损伤具有一定保护作用,其机制可能与激活AMPK和PI3K/Akt信号通路有关。     

Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial ischemic reperfusion injury

Hydroalcoholic extract of Dioscorea bulbifera (DB), a yam variety called air potato, was tested for its protective effect on myocardial ischemic/reperfusion (I/R) injury in rats due to apoptosis and necrosis. Myocardial I/R injury was induced by 30 min ischemia followed by 2 h reperfusion by perfusing isolated rat hearts with Krebs Henseilet bicarbonate (KHB) buffer in a Langendorff set up. Pretreatment of DB (150 mg kg(-1) body weight) for 30 days significantly reduced myocardial infarct size and improved the ventricular function (aortic flow and coronary flow, LVDP, LVmax dp/dt). Role of DB on apoptosis was also evaluated by determining caspase 3 as well as by examining pro-apoptotic and anti-apoptotic proteins Bax and Bcl2 by Western blot analysis followed by TUNEL assay. DB also prevented I/R-mediated down regulation of survival protein Akt and HO-1. Our results indicated that Dioscorea bulbifera could ameliorate myocardial ischemia and reperfusion injury by improving ventricular function and inhibition of cardiomyocyte necrosis and apoptosis.     

Dietary grape supplement ameliorates cerebral ischemia-induced neuronal death in gerbils

Oxidative damage has been implicated as one of the leading causes for neuronal cell death in a number of neurodegenerative diseases including stroke. Many vegetables and fruits are enriched in polyphenolic compounds known to exhibit antioxidant properties. This study is to investigate whether dietary supplement with grape powder (GP) may offer protection against neuronal damage due to global cerebral ischemia induced to Mongolian gerbils by occlusion of the common carotid arteries, a model known to cause delayed neuronal death (DND) in the hippocampal CA1 area. Gerbils were fed either a control diet (AIN76a) or a control diet supplemented with low (5.0 g/kg diet) or high (50 g/kg diet) levels of GP for two months. Four days after ischemia/reperfusion (I/R), the extent of DND, glial cell activation, nuclear DNA oxidation, and apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) reaction in hippocampal CA1 region were assessed. Ischemia-induced extensive DND in the CA1 region was accompanied by oxidative and fragmented DNA damage and a marked increase in reactive astrocytes and microglial cells. Dietary GP supplementation significantly protected neurons against I/R-induced DND, DNA damage, and apoptosis as well as attenuated glial cell activation. These results demonstrate that due to the antioxidant properties of polyphenols in GP, nutritional diets supplemented with grape can protect the brain against ischemic damage. The neuroprotective effects of GP supplement may have wide implication in the future for prevention/protection against other neurodegenerative damage.     

鞣花酸对马兜铃酸I诱导小鼠急性肾损伤的保护作用

目的:研究鞣花酸(ellagic acid,EA)对马兜铃酸I(aristolochic acids I,AAI)诱导的急性肾损伤的保护作用.方法:40只昆明小鼠(雌雄各半)随机分为健康组、模型组(10?mg/kg?mb?AAI)、EA低剂量组(10?mg/kg mb?AAI+10?mg/kg?mb?EA)和EA高剂量...     

Antioxidant and cardioprotective effects of Ilex brasiliensis: A comparative study with Ilex paraguariensis (yerba mate)

Our objective was to compare the antioxidant properties and cardiovascular effects in ischemia–reperfusion of leaves aqueous extracts of Ilex brasiliensis (B) and Ilex paraguariensis (P). In vitro systems were used to assess the antioxidant properties of the extracts. Isolated rat hearts were treated with both extracts before ischemia and myocardial function was assessed. Thiobarbituric acid reactive substances (TBARS) concentration and reduced glutathione (GSH) were also measured. B extract showed higher total phenols and ascorbic acid contents and a higher scavenging activity of peroxynitrite and ferric reducing antioxidant power (FRAP) than P extract. Postischemic systolic and diastolic functions were improved after B and P treatment. Both extracts decreased TBARS and preserved GSH content.The present study demonstrates that an aqueous extract of I. brasiliensis, similar to I. paraguariensis, protects the myocardium against ischemia–reperfusion injury and attenuates oxidative damage. These effects may be attributed to the potent antioxidant properties of the extract.     

Involvement of ERK,Akt and JNK signalling in H2O2‐induced cell injury and protection by hydroxytyrosol and its metabolite homovanillic alcohol

The olive oil polyphenol, hydroxytyrosol (HT), is believed to be capable of exerting protection against oxidative kidney injury. In this study we have investigated the ability of HT and its O‐methylated metabolite, homovanillic alcohol (HVA) to protect renal cells against oxidative damage induced by hydrogen peroxide. We show that both compounds were capable of inhibiting hydrogen peroxide‐induced kidney cell injury via an ability to interact with both MAP kinase and PI3 kinase signalling pathways, albeit at different concentrations. HT strongly inhibited death and prevented peroxide‐induced increases in ERK1/2 and JNK1/2/3 phosphorylation at 0.3 μM, whilst HVA was effective at 10 μM. At similar concentrations, both compounds also prevented peroxide‐induced reductions in Akt phosphorylation. We suggest that one potential protective effect exerted by olive oil polyphenols against oxidative kidney cell injury may be attributed to the interactions of HT and HVA with these important intracellular signalling pathways.     

The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury

Liver injuries can trigger a cascade of inflammatory responses and as a result, initiate the process of hepatic regeneration and fibrogenesis. Resveratrol (RSV) has multiple health‐promoting benefits. This study evaluated the potential protective effects and mechanism of RSV as related to cholestatic liver injury. RSV was given (4 mg/kg/day, i.p.) for either 3 days or 7 days after bile duct ligation (BDL) injury. RSV significantly reduced serum ALT, AST but not T‐bil on Day 3. At this early stage of injury, RSV significantly reduced TNF‐α and IL‐6 mRNA and decreased the number of Kupffer cells (CD68⁺) recruited in the injured liver. RSV decreased hepatic fibrosis and reduced collagen Iα1 and TIMP‐1 mRNA on Day 7. At the later stages of injury, RSV increased the number of Ki67⁺ hepatocytes indicating that RSV promoted hepatocyte proliferation. Additionally, it resulted in decreased expression of 4‐hydroxynonenal and increased expression of the hepatocyte growth factor protein and mRNA in the RSV‐treated BDL group. Meanwhile, RSV reduced the mortality rate of BDL mice. In conclusion, RSV attenuated inflammation and reduced Kupffer cells activation. RSV decreased fibrosis and promoted hepatocyte regeneration, which increased the survival of BDL mice. RSV was beneficial for the treatment of cholestatic liver injury.     

In vitro and in vivo protective effects of gingenosides on acute renal injury induced by cantharidin

Ginsenosides are major active constituent of Panax ginseng which is a popularly used functional food or drug in several Asian countries. The effects of ginsenosides on the renal dysfunction and injury caused by cantharidin were investigated in vitro and in vivo. Ginsenosides inhibited the cytotoxicity in rat normal kidney NRK cell induced by cantharidin. Cantharidin caused NRK cell apoptosis accompanied with decreasing bcl-2 expression. Pretreatment of ginsenosides reduced apoptosis rate and increased bcl-2 expression. In experimental rats, administration of cantharidin (0.14 mg/kg) for 15 days induced renal damage, which was evident from significantly increased levels of serum creatinine, urine protein and urea nitrogen. Pretreatment of ginsenosides reduced the increases of serum creatinine, urine protein, urea nitrogen and histological change in rats. These findings provide the evidence that ginsenosides might be useful in enhancing the tolerance of the kidney against renal injury associated with cantharidin.     

Predicting adult fish acute lethality with the zebrafish embryo: relevance of test duration, endpoints, compound properties, and exposure concentration analysis

The zebrafish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, which is required by various regulations for environmental risk assessment of chemicals. We investigated the reliability of the embryo test by probing organic industrial chemicals with a wide range of physicochemical properties, toxicities, and modes of toxic action. Moreover, the relevance of using measured versus nominal (intended) exposure concentrations, inclusion of sublethal endpoints, and different exposure durations for the comparability with reported fish acute toxicity was explored. Our results confirm a very strong correlation of zebrafish embryo to fish acute toxicity. When toxicity values were calculated based on measured exposure concentrations, the slope of the type II regression line was 1 and nearly passed through the origin (1 to 1 correlation). Measured concentrations also explained several apparent outliers. Neither prolonged exposure (up to 120 h) nor consideration of sublethal effects led to a reduced number of outliers. Yet, two types of compounds were less lethal to embryos than to adult fish: a neurotoxic compound acting via sodium channels (permethrin) and a compound requiring metabolic activation (allyl alcohol).     

Beneficial effects of sulfated polysaccharides from Sargassum wightii against mitochondrial alterations induced by Cyclosporine A in rat kidney

Sulfated polysaccharides from marine seaweeds are receiving continuous attention owing to their wide therapeutic applications and are known to inhibit free radical generation. It has been well known that mitochondria are the major sources as well as the target of free radicals. The renal tubules have high density of mitochondria and therefore show structural and functional defects in acute renal failure. Hence, the present study is designed to appraise the mitochondrial status during Cyclosporine A (CsA)-induced nephrotoxicity and the effect of sulfated polysaccharides over it. Sulfated polysaccharides (5 mg/kg body weight, subcutaneously) treatment significantly prevented the CsA-induced (25 mg/kg body weight, orally) mitochondrial damage. CsA-induced mitochondrial oxidative stress in rat kidney was evident from increased reactive oxygen species level, decreased antioxidant defense system, coupled with enhanced lipid peroxidation. Further, the activities of tricarboxylic acid cycle and electron transport chain enzymes were decreased in CsA-induced rats, along with a significant increase in the activities of urinary enzymes, thus indicating renal tubular injury. Ultrastructural changes were also in accord with the above aberrations. The above abnormalities were favorably modulated by sulfated polysaccharides supplementation, thus highlighting the significance of sulfated polysaccharides in preventing the renal mitochondrial dysfunction allied with CsA-provoked nephrotoxicity.     

Effect of prepartum energy balance on neutrophil function following pegbovigrastim treatment in periparturient cows

Treatment with granulocyte colony-stimulating factor (G-CSF) increases polymorphonuclear cell (neutrophil) count and enhances neutrophil function in the periparturient cow. Prepartum undernutrition was hypothesized to reduce the effect of a commercially available recombinant bovine G-CSF product (pegbovigrastim) on neutrophil count and function. Hence this study was undertaken to test the effect of undernutrition for approximately 1 mo before calving on the innate immune response to pegbovigrastim. Cows (n = 99) on pasture were blocked by expected calving date and body condition score and randomly assigned in a 2 × 2 factorial design. The first factor was that cows were fed to exceed energy requirements prepartum (full feeding) or restricted to approximately 85% of prepartum energy requirements (restricted feeding). The second factor was that at approximately 7 d before expected calving date, half the cows in each feed group were injected with pegbovigrastim and the remaining half were injected with saline. Treatments were repeated on the day of calving. Blood samples were collected pre- and postcalving for complete blood count, biochemistry, and in vitro assessment of neutrophil function including phagocytosis, myeloperoxidase release, and oxidative burst. Prepartum energy restriction resulted in lower body weight, a higher proportion of cows with elevated concentrations (i.e., >0.4 mmol/L) of fatty acids, and higher average β-hydroxybutyrate concentrations before calving relative to fully fed cows. Treatment with pegbovigrastim increased the total white cell, neutrophil, lymphocyte, and monocyte counts. Pegbovigrastim treatment resulted in increased release of myeloperoxidase by neutrophils. Prepartum feeding group did not have an effect, and no feeding group × treatment interaction was observed for any of the white cell counts or functional tests. We concluded that pegbovigrastim treatment results in significant increases in neutrophil count and enhances neutrophil function as indicated by increased myeloperoxidase release. The response to pegbovigrastim was not affected by restricted prepartum energy intake.     

桔甘片对急性酒精性肝损伤小鼠的保护作用

探讨桔甘片（Jie-Gan Tablets,JGT）对急性酒精肝损伤小鼠的保护作用。采取50%酒精一次性灌胃（i.g）的方法建立小鼠急性酒精性肝损伤模型。检测小鼠血清中谷草转氨酶（AST）、谷丙转氨酶（ALT）、甘油三酯（TG）水平,肝组织匀浆中丙二醛（MDA）的含量及谷胱甘肽过氧化酶（GSH-Px）的活性,采用H&E染色分析组织切片形态变化,评估JGT的肝保护作用。结果显示不同剂量JGT和联苯双酯预处理能够显著抑制小鼠体内两种血清转氨酶水平的升高（p<0.05）,抑制率最高达到61.81%。JGT高剂量组显著降低血清中TG水平（p<0.05）,降幅达到34.73%。与模型组相比,阳性对照组显著逆转了MDA水平上升这一现象（p<0.01）,JGT各给药组呈剂量依赖的方式降低MDA的含量（p<0.05）,且提高了抗氧化酶GSH-Px的活性（p<0.05）,其中高剂量组MDA含量降至1.74 nmol/mg,GSH-Px活力上升至828.81 U/mg pro。H&E染色结果表明,JGT预处理能够有效改善酒精诱导的肝损伤。由此可见,JGT对ALD具有一定的预防保护作用。     

Short communication: Effects of supplementing diets of Holsteins with copper,zinc, and manganese on blood neutrophil function

The effects of supplementing diets with sulfate or glycinate Cu, Zn, and Mn on blood neutrophil function were examined in 27 late-lactation Holstein cows having a mean (± standard deviation) days in milk at time of neutrophil assays of 216 ± 31 d. Cows were assigned to 9 blocks of 3 and were grouped by parity, milk production, and days in milk. Cows within each block were randomly assigned to 1 of 3 treatments: (1) control diet devoid of supplemental Cu, Zn, and Mn; (2) diet supplemented with Cu, Zn, and Mn via sulfates; and (3) diet supplemented with Cu, Zn, and Mn via glycinate form. All cows were initially fed a control total mixed ration with basal mineral concentrations of 8 mg/kg of Cu, 35 mg/kg of Zn, and 35 mg/kg of Mn for 30 d. During the treatment period, cows fed diets with mineral supplementation via sulfates or glycinate forms had target total dry matter dietary concentrations of 18 mg/kg of Cu, 60 mg/kg of Zn, and 60 mg/kg of Mn for 30 d. Control cows were fed the control diet devoid of supplemental minerals for an additional 30 d. In vitro neutrophil functions were measured after 30 d on experimental or control diets. Percentage of neutrophils phagocytizing, intracellular kill, and phagocytic index did not differ among treatments. Serum concentrations of Cu, Zn, and Mn were also not affected by dietary treatment after 30 d. Results from this study demonstrated that dietary Cu, Zn, and Mn supplemented either as sulfates or glycinate form for 30 d had no effect on either in vitro blood neutrophil function or serum concentrations of Cu, Zn, and Mn in late-lactation Holstein cows.     

Effects of differential supplementation of fatty acids during the peripartum and breeding periods of Holstein cows: II. Neutrophil fatty acids and function, and acute phase proteins

The objectives were to evaluate the effects of differential supplementation of Ca salts (CS) of fatty acids (FA) on plasma acute phase proteins and both FA composition and function (i.e., activity and cytokine production) of neutrophils, during the peripartum and breeding periods. Holstein cows were assigned randomly to receive either CS of palm (PO) or safflower (SO) oils from 30 d prepartum until 35 d postpartum (dpp) and CS of PO or fish oil (FO) from 35 to 160 dpp. Supplementation of CS of FA was at 1.5% of dietary dry matter. Cows (n = 32) were sampled three times weekly from parturition to 35 dpp for analyses of plasma concentrations of haptoglobin and fibrinogen. Cows (n = 47) were sampled for neutrophil phagocytic and oxidative burst activities toward Escherichia coli and Staphylococcus aureus, and neutrophil abundances of L-selectin and β₂-integrin assessed by flow cytometry at 32 d prepartum, within 7 h after parturition, and 4 and 7 dpp. Profiles of FA in neutrophils and cytokine production (i.e., tumor necrosis factor alpha, TNF-α, and IL-1β) were assessed prepartum (n = 14), 35 (PO vs. SO; n = 26) and 85 dpp (PO vs. FO; n = 28). Plasma concentrations of haptoglobin and fibrinogen were greater for cows fed SO compared with PO. The percentage of neutrophils with phagocytic and oxidative burst activities was not affected by transition diets, but activities per neutrophil were greater in SO compared with PO diets at 4 (phagocytosis and oxidative burst) and 7 dpp (oxidative burst). Neutrophil abundance of L-selectin, but not β₂-integrin, was greater in SO compared with PO at 4 and 7 dpp. Neutrophil productions of TNF-α and IL-1β were increased at 35 dpp in SO compared with PO diets, but production of TNF-α was attenuated in FO compared with PO at 85 dpp. Neutrophil ratios of n-6:n-3 FA were greater at 35 dpp in the SO diet and less at 85 dpp in FO compared with PO diets. In conclusion, cows supplemented with CS of SO had improved innate immunity (i.e., acute phase response and neutrophil function) to better cope with the bacterial challenges in the postpartum period. Conversely, CS of FO attenuated neutrophil cytokine production.     

四氢姜黄素经PI3K/Akt信号通路对人血小板活化和聚集的调控作用

目的：探讨姜黄素的主要肠道代谢物四氢姜黄素（tetrahydrocurcumin，THC）对血小板活化和聚集的影响及其可能的分子机制。方法：在体外实验中，用不同浓度的THC（0、0.5、1、10 μmol/L）提前与健康人纯化血小板共同孵育40 min，然后加入凝血酶激活血小板2 min，用流式细胞术测定血小板表面CD62P和CD63的表达量，用酶联免疫吸附法测定血小板释放血小板因子-4（platelet factor-4，PF4）和趋化因子配体-5（chemokine ligand 5，CCL5）水平，用血小板聚集仪检测血小板释放ATP水平和血小板最大聚集率，用Western blot蛋白免疫印迹法检测血小板磷酸肌醇-3-激酶（phosphoinositide 3-kinase，PI3K）和Akt蛋白的磷酸化水平。结果：与模型组（血小板悬液中加入0.05%二甲基亚砜）相比，THC能抑制凝血酶诱导的血小板表面CD62P和CD63的表达，抑制PF4、CCL5和ATP的释放，降低血小板最大聚集率，下调PI3K和Akt蛋白的磷酸化水平，且呈浓度依赖效应，其中10 μmol/L的浓度下作用效果显著（P＜0.01、P＜0.001）。PI3K的特异性激动剂740 Y-P可部分逆转THC对PF4和CCL5释放和血小板聚集的抑制作用（P＜0.05、P＜0.01）。结论：THC具有显著抑制血小板活化和聚集的作用，其机制可能是THC可下调PI3K/Akt介导的信号通路。