重组人红细胞生成素对慢性肾衰大鼠的疗效

建立慢性肾衰贫血大鼠的动物模型后 ,分别用基因重组人红细胞生成素 (r Hu EPO)按 45 0 IU /kg、15 0 IU /kg、 5 0 IU /kg 3组剂量连续 14d皮下注射上述大鼠 ,同时设立阳性对照组及阴性对照组。结果发现r Hu EPO只能治疗肾衰造成的贫血 ,而对肾衰无治疗作用。     

慢性热应激对大鼠肝脏miRNA的影响

目的分析慢性热应激对大鼠肝脏mi RNA的影响。方法将Wister雄性大鼠随机分为慢性热应激组和常温对照组,提取各组大鼠肝脏组织总RNA,反转录合成c DNA,以其为模板,应用q RT-PCR方法检测大鼠肝脏组织中mir92a、mir151、mir425、mir328a、mir210、mir98的表达。结果与常温对照组相比,慢性热应激组大鼠肝脏组织中mir151、mir425、mir98、mir328a和mir210的相对表达量均明显升高(P0.01),而mir-92a则略有升高(P0.05)。结论慢性热应激大鼠肝脏组织中有5种mi RNA相对表达量明显升高,为日后慢性热应激标志物的寻找和抗热应激药物的研发奠定了基础。     

地中海贫血儿童的预防接种建议及探讨

地中海贫血又称"珠蛋白生成障碍贫血",是由于一种或多种珠蛋白肽链合成受阻或完全抑制,导致Hb成分组成异常引起的慢性溶血性贫血,其中以α、β-地中海贫血较常见,α-地中海贫血有静止型、标准型、中间型及Hb Bart胎儿水肿综合征4种临床分型;β-地中海贫血有轻型、中间型及重型3种临床类型[1]。该贫血为全球分布最广、累积人数最多的常染色体隐性单基因遗传病,在中国广东、广西、海南发病率较高。     

滁菊挥发油的抗炎实验研究

为研究滁菊挥发油的抗炎作用,采用二甲苯致小鼠耳廓肿胀、蛋清致大鼠足跖肿胀、大鼠纸片肉芽肿模型观察滁菊挥发油对急、慢性炎症的影响。结果表明,滁菊挥发油对二甲苯致小鼠耳廓肿胀、蛋清致大鼠足跖肿胀和大鼠纸片肉芽肿等急、慢性炎症均有明显的抑制作用。     

2～4期慢性肾脏病贫血临床观察

目的探讨慢性肾脏病(CKD)2～4期贫血的原因与治疗。方法观察60例CKD2～4期患者血象、骨髓象红细胞、血清铁及总铁结合力等指标。并随机分为A、B2组,2组均常规抗贫血治疗,A组加服促红素生成方。结果 CKD2～4期患者多为轻度贫血,少数无贫血或中度贫血者骨髓象红细胞增生活跃,表现为增生性贫血。血清铁含量减低而总铁结合力升高。配合抗贫血及中药治疗可明显提高血红蛋白含量。结论 CKD2～4期贫血原因之一系铁缺乏引起。治疗上应适当补充铁剂,配合其他相应措施如EPO、中草药等。     

复肝肽口服液对大鼠四氯化碳慢性肝损伤的保护作用

目的观察复肝肽口服液(主要成分为新生牛肝活性肽)对大鼠四氯化碳(CCl4)慢性肝损伤的保护作用。方法制备大鼠CCl4慢性肝损伤模型,观察复肝肽口服液对慢性肝损伤大鼠红、白细胞数、血色素、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)、白蛋白(ALB)、白球蛋白比例(A/G)的影响。结果与模型对照组比较,复肝肽3个剂量组大鼠的A/G值均明显升高,肝组织病变明显减轻,高剂量组ALT、AST明显降低。结论复肝肽口服液对慢性肝损伤有明显的保护作用。     

丹参注射液对慢性胰腺炎的治疗作用

目的探讨丹参注射液对慢性胰腺炎大鼠血清中HA和LN的影响,从而验证丹参注射液对慢性胰腺炎的治疗作用。方法通过胰管内注射2%三硝基苯磺酸的方法建立大鼠慢性胰腺炎纤维化模型。50只雄性SD大鼠随机分成5组:正常组、模型组、丹参小剂量组(400mg/kg)、丹参中剂量组(800mg/kg)、丹参大剂量组(1600mg/kg)。4周后应用免疫组化法(ELLSA)检测大鼠血清中的HA和LN的表达情况,同时将胰腺组织行HE染色,观察病理形态学改变。结果模型组发生明显的胰腺纤维化,血清中的HA和LN的表达明显升高。各不同剂量干预组纤维化程度及HA和LN的表达均低于模型组。结论丹参注射液可抑制大鼠胰腺纤维化组织的形成,对慢性胰腺炎有一定的治疗作用。     

ClC-2氯通道在大鼠小梁网中的表达

目的分析电压门控性氯通道ClC家族中的ClC-2氯通道在大鼠小梁网中的表达,探讨ClC-2在青光眼发病机制中的可能作用。方法经前房内注射玻璃酸钠建立大鼠慢性高眼压模型,取正常大鼠及模型大鼠小梁网组织,采用RT-PCR法检测ClC-2基因mRNA的转录水平,免疫组化法检测ClC-2蛋白的表达水平。结果在正常大鼠和慢性高眼压模型大鼠小梁网组织中,均可检测到ClC-2的表达,且模型大鼠ClC-2基因mRNA的转录水平和蛋白的表达水平均较正常大鼠降低。结论大鼠小梁组织中存在ClC-2氯通道的表达,该通道的表达受小梁网的一些病理因素的影响。     

制蚜菌素毒性研究

研究制蚜菌素的急性、亚慢性毒性及致突变性结果表明,急性经口LD50雌雄性大鼠均为38.3mg/kg,雄性小鼠为38.3mg/kg,雌性小鼠为17.8mg/kg,急性经皮LD50雄性大鼠为1470mg/kg,雌性大鼠为1210mg/kg;小鼠骨髓多染红细胞微核试验、小鼠睾丸精母细胞染色体畸变试验及Ames试验结果均为阴性。大鼠亚慢性经口毒性无作用剂量雄性大鼠为(0.18±0.01)mg/(kg.d),雌性大鼠为(0.22±0.02)mg/(kg.d)。     

生物农药阿维菌素的NEL和ADI研究

研究了阿维菌素原药的急性和亚慢性毒性及致突变性。结果显示,大鼠经口LD50雌雄性均为21.5mg/kg,小鼠经口LD50雌性为68.1mg/kg,雄性为38.3mg/kg,大鼠经皮LD50雌雄性均大于2000mg/kg。家兔急性皮肤刺激试验,对皮肤的刺激强度属无刺激性。家兔眼刺激试验,对眼的刺激强度属轻度刺激性。小鼠骨髓多染红细胞微核试验和小鼠睾丸精母细胞染色体畸变试验均为阴性。大鼠亚慢性经口毒性试验,21.5mg/kg饲料组雌性大鼠体重增加量低于对照组,雌雄性大鼠食物利用率低于对照组,雌雄性大鼠心/体比、肺/体比、肾/体比高于对照组,雌性大鼠脑/体比高于对照组,雄性大鼠脾/体比低于对照组,雌雄性大鼠血液生化指标ALB、GLU高于对照组。最大无作用剂量(NEL)为:雌性大鼠(0.796±0.062)mg/kg·d,雄性大鼠(0.635±0.056)mg/kg·d。若以安全系数100倍考虑,人的每日允许摄入量(ADI)应为0.0058mg/kg·bw。     

Cyclic nucleotide signalling in kidney fibrosis

Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure.     

The Diabetic Cardiorenal Nexus

The end-stage of the clinical combination of heart failure and kidney disease has become known as cardiorenal syndrome. Adverse consequences related to diabetes, hyperlipidemia, obesity, hypertension and renal impairment on cardiovascular function, morbidity and mortality are well known. Guidelines for the treatment of these risk factors have led to the improved prognosis of patients with coronary artery disease and reduced ejection fraction. Heart failure hospital admissions and readmission often occur, however, in the presence of metabolic, renal dysfunction and relatively preserved systolic function. In this domain, few advances have been described. Diabetes, kidney and cardiac dysfunction act synergistically to magnify healthcare costs. Current therapy relies on improving hemodynamic factors destructive to both the heart and kidney. We consider that additional hemodynamic solutions may be limited without the use of animal models focusing on the cardiomyocyte, nephron and extracellular matrices. We review herein potential common pathophysiologic targets for treatment to prevent and ameliorate this syndrome.     

Fibrosis of Peritoneal Membrane as Target of New Therapies in Peritoneal Dialysis

Peritoneal dialysis (PD) is an efficient renal replacement therapy for patients with end-stage renal disease. Even if it ensures an outcome equivalent to hemodialysis and a better quality of life, in the long-term, PD is associated with the development of peritoneal fibrosis and the consequents patient morbidity and PD technique failure. This unfavorable effect is mostly due to the bio-incompatibility of PD solution (mainly based on high glucose concentration). In the present review, we described the mechanisms and the signaling pathway that governs peritoneal fibrosis, epithelial to mesenchymal transition of mesothelial cells, and angiogenesis. Lastly, we summarize the present and future strategies for developing more biocompatible PD solutions.     

Effect of platelet-activating factor antagonist BN 52063 on the nephrotoxicity of cisplatin

Cisplatin (DDP) is an effective anticancer agent that has been successfully applied against various solid tumors. However, DDP commonly causes nephrotoxicity. We observed that DDP led to significant alterations in renal microcirculation when administered to Munich-Wistar rats, with a concomitant decrease in single nephron glomerular filtration rate due to reduction in glomerular plasma flow and transcapillary hydraulic pressure difference. BN 52063, a platelet-activating factor antagonist, caused a striking change in acute renal failure induced by DDP leading toward normalization of all parameters of renal function. The results suggest that BN 52063 could be used as a novel drug to control DDP nephrotoxicity. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

Impact of Sodium–Glucose Co-Transporter 2 Inhibitors on Cardiac Protection

Sodium–glucose co-transporter 2 (SGLT2) inhibitors have been approved as a new class of anti-diabetic drugs for type 2 diabetes mellitus (T2DM). The SGLT2 inhibitors reduce glucose reabsorption through renal systems, thus improving glycemic control in all stages of diabetes mellitus, independent of insulin. This class of drugs has the advantages of no clinically relevant hypoglycemia and working in synergy when combined with currently available anti-diabetic drugs. While improving sugar level control in these patients, SGLT2 inhibitors also have the advantages of blood-pressure improvement and bodyweight reduction, with potential cardiac and renal protection. In randomized control trials for patients with diabetes, SGLT2 inhibitors not only improved cardiovascular and renal outcomes, but also hospitalization for heart failure, with this effect extending to those without diabetes mellitus. Recently, dynamic communication between autophagy and the innate immune system with Beclin 1-TLR9-SIRT3 complexes in response to SGLT2 inhibitors that may serve as a potential treatment strategy for heart failure was discovered. In this review, the background molecular pathways leading to the clinical benefits are examined in this new class of anti-diabetic drugs, the SGLT2 inhibitors.     

Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats

Renal ischaemia reperfusion (I/R) triggers a cascade of events including oxidative stress, apoptotic body and microparticle (MP) formation as well as an acute inflammatory process that may contribute to organ failure. Macrophages are recruited to phagocytose cell debris and MPs. The tyrosine kinase receptor MerTK is a major player in the phagocytosis process. Experimental models of renal I/R events are of major importance for identifying I/R key players and for elaborating novel therapeutical approaches. A major aim of our study was to investigate possible involvement of MerTK in renal I/R. We performed our study on both natural mutant rats for MerTK (referred to as RCS) and on wild type rats referred to as WT. I/R was established by of bilateral clamping of the renal pedicles for 30′ followed by three days of reperfusion. Plasma samples were analysed for creatinine, aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), kidney injury molecule -1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels and for MPs. Kidney tissue damage and CD68-positive cell requirement were analysed by histochemistry. monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and histone 3A (H3A) levels in kidney tissue lysates were analysed by western blotting. The phagocytic activity of blood-isolated monocytes collected from RCS or WT towards annexin-V positive bodies derived from cultured renal cell was assessed by fluorescence-activated single cell sorting (FACS) and confocal microscopy analyses. The renal I/R model for RCS rat described for the first time here paves the way for further investigations of MerTK-dependent events in renal tissue injury and repair mechanisms.     

Multi-Organ Protective Effects of Sodium Glucose Cotransporter 2 Inhibitors

Sodium glucose cotransporter 2 inhibitors (SGLT2i) block the reabsorption of glucose by inhibiting SGLT2, thus improving glucose control by promoting the renal excretion of glucose, without requiring insulin secretion. This pharmacological property of SGLT2i reduces body weight and improves insulin resistance in diabetic patients. Such beneficial metabolic changes caused by SGLT2i are expected to be useful not only for glucose metabolism, but also for the protection for various organs. Recent randomized controlled trials (RCTs) on cardiovascular diseases (EMPA-REG OUTCOME trial and CANVAS program) showed that SGLT2i prevented cardiovascular death and the development of heart failure. RCTs on renal events (EMPA-REG OUTCOME trial, CANVAS program, and CREDENCE trial) showed that SGLT2i suppressed the progression of kidney disease. Furthermore, SGLT2i effectively lowered the liver fat content, and our study demonstrated that SGLT2i reduced the degree of hepatic fibrosis in patients at high-risk of hepatic fibrosis. Such promising properties of SGLT2i for cardiovascular, renal, and hepatic protection provide us the chance to think about the underlying mechanisms for SGLT2i-induced improvement of multiple organs. SGLT2i have various mechanisms for organ protection beyond glucose-lowering effects, such as an increase in fatty acids utilization for hepatic protection, osmotic diuresis for cardiac protection, an improvement of insulin resistance for anti-atherogenesis, and an improvement of tubuloglomerular feedback for renal protection.     

Detection of Abnormal Extracellular Matrix in the Interstitium of Regenerating Renal Tubules

Stem/progenitor cells are promising candidates for the regeneration of parenchyma in acute and chronic renal failure. However, recent data exhibit that survival of stem/progenitor cells after implantation in diseased renal parenchyma is restricted. To elaborate basic parameters improving survival, cell seeding was simulated under advanced in vitro conditions. After isolation, renal stem/progenitor cells were mounted in a polyester interstitium for perfusion culture. During generation of tubules, chemically defined CO₂ Independent Medium or Leibovitz’s L-15 Medium was applied. Specimens were then fixed for transmission electron microscopy to analyze morphological features in generated tubules. Fixation in conventional glutaraldehyde (GA) solution shows development of tubules each exhibiting a polarized epithelium, an intact basal lamina and an inconspicuous interstitium. In contrast, special fixation of specimens in GA solution containing cupromeronic blue, ruthenium red or tannic acid unveils previously not visible extracellular matrix. Control experiments elucidate that a comparable extracellular matrix is not present in the interstitium of the matured kidney. Thus, generation of renal tubules in combination with advanced fixation of specimens for electron microscopy demonstrates that development of abnormal features in the newly developed interstitium has to be considered, when repair of renal parenchyma is performed by implantation of stem/progenitor cells.     

The Human Host Defense Ribonucleases 1, 3 and 7 Are Elevated in Patients with Sepsis after Major Surgery—A Pilot Study

Sepsis is the most common cause of death in intensive care units and associated with widespread activation of host innate immunity responses. Ribonucleases (RNases) are important components of the innate immune system, however the role of RNases in sepsis has not been investigated. We evaluated serum levels of RNase 1, 3 and 7 in 20 surgical sepsis patients (Sepsis), nine surgical patients (Surgery) and 10 healthy controls (Healthy). RNase 1 and 3 were elevated in Sepsis compared to Surgery (2.2- and 3.1-fold, respectively; both p < 0.0001) or compared to Healthy (3.0- and 15.5-fold, respectively; both p < 0.0001). RNase 1 showed a high predictive value for the development of more than two organ failures (AUC 0.82, p = 0.01). Patients with renal dysfunction revealed higher RNase 1 levels than without renal dysfunction (p = 0.03). RNase 1 and 3 were higher in respiratory failure than without respiratory failure (p < 0.0001 and p = 0.02, respectively). RNase 7 was not detected in Healthy patients and only in two patients of Surgery, however RNase 7 was detected in 10 of 20 Sepsis patients. RNase 7 was higher in renal or metabolic failure than without failure (p = 0.04 and p = 0.02, respectively). In conclusion, RNase 1, 3 and 7 are secreted into serum under conditions with tissue injury, such as major surgery or sepsis. Thus, RNases might serve as laboratory parameters to diagnose and monitor organ failure in sepsis.