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。     

新生牛肝活性肽对小鼠的免疫增强作用

目的观察新生牛肝活性肽对小鼠免疫功能的调节作用。方法采用清洁级ICR小鼠,分别经口给予2.08、4.16和12.48ml/kg3个剂量的新生牛肝活性肽,以生理盐水为对照组,通过淋巴细胞转化试验、小鼠迟发型变态反应试验、血清溶血素测定、抗体生成细胞检测、小鼠碳廓清试验、腹腔巨噬细胞吞噬鸡红细胞试验及NK细胞活性测定来评价其对小鼠的免疫增强作用。结果3个剂量组均能促进淋巴细胞增殖,中、高剂量组能增强小鼠迟发型变态反应强度和小鼠血清溶血素作用,提高溶血空斑数及NK细胞活性,但对小鼠的碳廓清能力及腹腔巨噬细胞的吞噬能力无明显影响。结论新生牛肝活性肽能增强小鼠的免疫功能。     

珍珠粉对小鼠酒精肝的保护作用的实验研究

目的观察珍珠粉对小鼠酒精肝的保护作用。方法采用食用酒精诱导小鼠肝损伤,比色法测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的含量;肝脏中超氧化物歧化酶(SOD)活力和丙二醛(MDA)浓度,计算肝脏指数。结果珍珠粉高剂量可使小鼠酒精肝损伤血清ALT、AST升高的水平降低,降低小鼠肝损伤的肝脏MDA的水平,提高SOD的活性,降低升高的肝脏指数,与模型组比较均有显著差异(P<0.01)。结论珍珠粉对小鼠酒精肝有明显的保肝作用。     

新生牛肝活性肽的制备及其毒性检测

目的制备新生牛肝活性肽并评价其安全性。方法采用膜法分离制备新生牛肝活性肽。将3批制品于37～40℃,75%相对湿度条件下存放3个月,以多肽含量为指标观察其稳定性,并进行急性毒性试验、小鼠骨髓细胞微核试验、Ames试验、小鼠精子畸形试验和大鼠喂养试验。结果制备的3批新生牛肝活性肽存放3个月后,多肽含量无明显下降,质量稳定。小鼠和大鼠经口灌人大于20.0g/kg体重的新生牛肝活性肽,均无急性毒性。3种致突变试验均未显示出致突变性,大鼠喂养试验各项指标均未见明显毒性。结论新生牛肝活性肽未表现出明显毒性。     

紫花前胡素对CCl_4致小鼠肝损伤的保护作用

目的:观察紫花前胡素(Decursin)对四氯化碳(CCl_4)致小鼠急性肝损伤的改善作用并探讨其可能的机制。方法:50只健康雄性ICR小鼠随机分成5组,正常对照组,急性肝损伤模型组,紫花前胡素低、中、高剂量组。隔天灌胃给药,共30天;腹腔注射CCl_4玉米油溶液诱导小鼠急性肝损伤,处死取血和肝脏。测定各组小鼠血清中丙氨酸氨基转移酶(ALT)及天门冬氨酸氨基转移酶(AST)的活性,小鼠肝脏组织中CYP2E1的含量,在体外检测紫花前胡素清除超氧阴离子及羟自由基的能力。结果:不同剂量紫花前胡素能够抑制CCl_4引起的血清ALT及AST的升高,并且能够减少肝组织匀浆中CYP2E1的产生。此外,紫花前胡素在体外能够清除超氧阴离子及羟自由基。结论:紫花前胡素对CCl_4导致的小鼠急性肝损伤具有一定的保护作用,推测可能是通过抑制细胞色素酶CYP2E1的产生进而减少三氯甲基等自由基的产生以及自身的抗氧化能力实现预防和改善急性肝损伤。     

杜仲总黄酮对小鼠急性肝损伤的保护作用

研究了杜仲总黄酮对四氯化碳(CCl_4)诱导的急性肝损伤的保护作用。通过腹腔注射CCl_4诱导小鼠急性肝损伤,检测小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)的含量、肝脏中超氧化物歧化酶(SOD)的活性、谷胱甘肽(GSH)和丙二醛(MDA)的含量,考察杜仲总黄酮的保肝作用。结果表明:杜仲总黄酮能显著降低急性肝损伤小鼠血清中的ALT、AST活性与肝脏中的MDA含量,并能提高肝脏中的SOD与GSH活性。杜仲总黄酮对CCl_4引起的急性肝损伤小鼠具有保护作用,其作用机制可能与抗氧化作用有关。     

一种解酒护肝片对小鼠酒精性肝损伤的保护作用的研究

目的:研究解酒护肝片对小鼠急性酒精性肝损伤的保护作用。方法:将小鼠随机分为5组,正常组、模型组、解酒护肝片低剂量组、中剂量组、高剂量组。采用白酒灌胃造模,造模与给药同时进行。6周后测定血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、丙二醛(MDA)、甘油三酯(TG)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)水平。结果:各剂量解酒护肝片能显著降低小鼠血清ALT、AST活性和肝组织MDA、TG含量(P<0.05或P<0.01),提高肝组织SOD和GSH活性,各预防治疗组之间比较提示,以高剂量解酒护肝片作用最为显著。结论:解酒护肝片能有效预防小鼠酒精性肝病。     

白芍总苷降尿酸实验研究

目的:研究白芍总苷降尿酸作用。方法:采用60只雄性昆明种小鼠,随机分为正常对照组、高尿酸血症模型对照组、别嘌醇组(40mg·kg~(-1))及白芍总苷低剂量组(2g·kg~(-1))和高剂量组(4g·kg~(-1)),每组12只;20%酵母浸粉饲料喂养造模。于给药15d后测定血清尿酸(uric acid,UA)、肌酐(creatinine,Cr)和尿素氮(blood urea nitrogen,BUN)含量并测定肝脏组织中黄嘌呤氧化酶(xanthine oxidase,XOD)和腺苷脱氨酶(adenosine deaminase,ADA)的活性。结果:与模型对照组比较,白芍总苷低剂量组和高剂量组小鼠血清的UA水平降低(P0.05);白芍总苷低剂量组和高剂量组小鼠肝脏组织中XOD和ADA的活性降低(P0.05)。结论:白芍总苷对高尿酸血症小鼠模型具有保护作用。     

三叶香茶菜不同极性部位的保肝降酶活性筛选实验研究

目的:研究三叶香茶菜醇提取物及不同部位的保肝降酶活性作用。方法:水提醇沉法提取三叶香茶菜,柱色谱分离出样品,观察样品对CCl_4致急性肝损伤小鼠的作用。结果:三叶香茶菜水提醇沉物降低CCl_4致急性肝损伤小鼠血清ALT的作用,与模型组比较差异有统计学意义(P0.05);经过提取分离得到的其他样品对CCl_4致急性肝损伤小鼠血清ALT的作用不明显,与模型组比较差异无统计学意义(P0.05)。结论:三叶香茶菜水提醇沉物对CCl_4致急性肝损伤小鼠具有保护作用,而经柱色谱法分离获得的样品对CCl_4致急性肝损伤小鼠保护作用不明显。     

氧化苦参碱磷脂复合物对四氯化碳致小鼠慢性肾损伤的保护作用

目的考察氧化苦参碱磷脂复合物对四氯化碳致慢性肾损伤小鼠的保护作用。方法采用0.5%CCl_4橄榄油溶液灌胃造模,小鼠分为空白对照组、CCl_4模型组、氧化苦参碱组(78 mg/kg)、氧化苦参碱磷脂复合物低剂量组(39 mg/kg)、氧化苦参碱磷脂复合物中剂量组(78 mg/kg)、氧化苦参碱磷脂复合物高剂量组(156 mg/kg)。期间记录摄食量和体重,8周后检测血清中尿素氮(BUN)及肌酐(SCr)的含量。结果 CCl_4模型组BUN和SCr水平明显升高,氧化苦参碱各组BUN和SCr水平优于模型组。结论氧化苦参碱制成磷脂复合物后可以提高对小鼠肾损伤的保护治疗作用。     

Hepatoprotective and Antioxidant Effects of Licorice Extract against CCl(4)-Induced Oxidative Damage in Rats

Licorice has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. In this study, we evaluated the antihepatotoxic effect of licorice aqueous extract (LE) on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Hepatic damage, as reveled by histology and the increased activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and decreased levels of serum total protein (TP), albumin (Alb) and globulin (G) were induced in rats by an administration of CCl(4) at 3 mL/kg b.w. (1:1 in groundnut oil). Licorice extract significantly inhibited the elevated AST, ALP and ALT activities and the decreased TP, Alb and G levels caused by CCl(4) intoxication. It also enhanced liver super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), Glutathione S-transferase (GST) activities and glutathione (GSH) level, reduced malondialdehyde (MDA) level. Licorice extract still markedly reverses the increased liver hydroxyproline and serum TNF-α levels induced by CCl(4) intoxication. The data of this study support a chemopreventive potential of licorice extract against liver oxidative injury.     

激活素A及其ⅡA型受体在ConA诱导小鼠急性肝损伤时的表达及其作用

目的探讨激活素A(ActivinA)及其ⅡA型受体(ActRⅡA)在刀豆蛋白A(ConA)诱导小鼠急性肝损伤时的表达及其作用。方法尾静脉注射ConA诱导小鼠急性肝损伤,测定血清转氨酶水平判断肝脏组织损伤程度,实时定量RT-PCR检测ActivinA及ActRⅡAmRNA转录水平;应用抗ActivinA和ActRⅡA抗体进行阻断试验,测定血清转氨酶水平,HE染色观察肝组织病理学变化。结果ConA诱导的急性肝损伤模型小鼠血清转氨酶水平明显升高,ActivinA及ActRⅡAmRNA转录水平也明显高于对照组;体内应用抗ActivinA和ActRⅡA抗体阻断ActivinA和ActRⅡA的作用,均可不同程度减轻肝损伤。结论ActivinA是介导ConA诱导小鼠急性肝损伤的重要致病因子,阻断ActivinA的表达或其作用途径,可能成为治疗肝损伤疾病的有效靶点。     

Esculetin ameliorates carbon tetrachloride-mediated hepatic apoptosis in rats

Esculetin (ESC) is a coumarin that is present in several plants such as Fraxinus rhynchophylla and Artemisia capillaris. Our previous study found that FR ethanol extract (FR(EtOH)) significantly ameliorated rats' liver function. This study was intended to investigate the protective mechanism of ESC in hepatic apoptosis in rats induced by carbon tetrachloride. Rat hepatic apoptosis was induced by oral administration of CCl(4). All rats were administered orally with CCl(4) (20%, 0.5 mL/rat) twice a week for 8 weeks. Rats in the ESC groups were treated daily with ESC, and silymarin group were treated daily with silymarin. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) as well as the activities of the anti-oxidative enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase in the liver were measured. In addition, expression of liver apoptosis proteins and anti-apoptotic proteins were detected. ESC (100, 500 mg/kg) significantly reduced the elevated activities of serum ALT and AST caused by CCl(4) and significantly increased the activities of catalase, GPx and SOD. Furthermore, ESC (100, 500 mg/kg) significantly decreased the levels of the proapoptotic proteins (t-Bid, Bak and Bad) and significantly increased the levels of the anti-apoptotic proteins (Bcl-2 and Bcl-xL). ESC inhibited the release of cytochrome c from mitochondria. In addition, the levels of activated caspase-9 and activated caspase-3 were significantly decreased in rats treated with ESC than those in rats treated with CCl(4) alone. ESC significantly reduced CCl(4)-induced hepatic apoptosis in rats.     

Effects of Beverages on Alcohol Metabolism: Potential Health Benefits and Harmful Impacts

Nonalcoholic beverages are usually consumed accompanying alcoholic drinks, and their effects on alcohol metabolism are unclear in vivo. In this study, the effects of 20 nonalcoholic beverages on alcohol metabolism and liver injury caused by alcohol were evaluated in mice. Kunming mice were orally fed with alcohol (52%, v/v) and beverages. The concentrations of ethanol and acetaldehyde in blood as well as the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver were assessed to indicate alcohol metabolism. The levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) in serum as well as the levels of malonaldehyde (MDA) and superoxide dismutase (SOD) in liver were measured to reflect the alcohol-induced liver injury. The results showed that the treatment of soda water, green tea and honey chrysanthemum tea could accelerate ethanol metabolism and prevent liver injuries caused by alcohol when companied with excessive alcohol drinking. They might be potential dietary supplements for the alleviation of harmful effects from excessive alcohol consumption. On the contrary, some beverages such as fresh orange juice and red bull are not advised to drink when companied with alcohol consumption due to their adverse effects on ethanol induced liver injury.     

Recombinant Human HPS Protects Mice and Nonhuman Primates from Acute Liver Injury

Acute liver injury shares a common feature of hepatocytes death, immune system disorders, and cellular stress. Hepassocin (HPS) is a hepatokine that has ability to promote hepatocytes proliferation and to protect rats from D-galactose (D-Gal)- or carbon tetrachloride (CCl₄)-induced liver injury by stimulating hepatocytes proliferation and preventing the high mortality rate, hepatocyte death, and hepatic inflammation. In this paper, we generated a pharmaceutical-grade recombinant human HPS using mammalian cells expression system and evaluated the effects of HPS administration on the pathogenesis of acute liver injury in monkey and mice. In the model mice of D-galactosamine (D-GalN) plus lipopolysaccharide (LPS)-induced liver injury, HPS treatment significantly reduced hepatocyte death and inflammation response, and consequently attenuated the development of acute liver failure. In the model monkey of D-GalN-induced liver injury, HPS administration promoted hepatocytes proliferation, prevented hepatocyte apoptosis and oxidation stress, and resulted in amelioration of liver injury. Furthermore, the primary pharmacokinetic study showed natural HPS possesses favorable pharmacokinetics; the acute toxicity study indicated no significant changes in behavioral, clinical, or histopathological parameters of HPS-treated mice, implying the clinical potential of HPS. Our results suggest that exogenous HPS has protective effects on acute liver injury in both mice and monkeys. HPS or HPS analogues and mimetics may provide novel drugs for the treatment of acute liver injury.     

Hepatoprotective Effects of Berberis vulgaris L. Extract/β Cyclodextrin on Carbon Tetrachloride-Induced Acute Toxicity in Mice

The present study investigated the capacity of formulated Berberis vulgaris extract/β-cyclodextrin to protect liver against CCl(4)-induced hepatotoxicity in mice. Formulated and non-formulated extracts were given orally (50 mg/kg/day) to mice for 7 days and were then intra-peritoneally injected with 1.0 mL/kg CCl(4) on the 8th day. After 24 h of CCl(4) administration, an increase in the levels of apartate-amino-transferase (AST), alanine-amino-transferase (ALT) and malondialdehyde (MDA) was found and a significant decrease in superoxide-dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione-peroxidase (GPx) levels could be detected. This was accompanied by extended centrilobular necrosis, steatosis, fibrosis and an altered ultrastructure of hepatocytes. Pre-treatment with formulated or non-formulated extract suppressed the increase in ALT, AST and MDA levels and restored the level of antioxidant enzymes at normal values. Histopathological and electron-microscopic examination showed milder liver damage in both pre-treated groups and the protective effect was more pronounced after the formulated extract was administered. Internucleosomal DNA fragmentation induced by CCl(4) was reduced in the group which received non-formulated extract and absent in the group which received formulated extract. Taken together, our results suggest that Berberis vulgaris/β-cyclodextrin treatment prevents hepatic injury induced by CCl(4) and can be considered for further nutraceutical studies.