水飞蓟宾-磷脂酰胆碱复合物对小鼠急性肝损伤保护作用的量效关系

目的　观察不同剂量水飞蓟宾 -磷脂酰胆碱复合物 (SPC)对四氯化碳 (CCl4)所致小鼠急性肝损伤的影响。方法　雌性小鼠随机分组给药后测定血清中谷丙转氨酶 (ALT)和谷草转氨酶 (AST)活性 ,取肝组织作病理学检查。结果　不同剂量的水飞蓟宾 -磷脂酰胆碱复合物均可明显降低CCl4所致小鼠血清中ALT和AST活性升高 ,并与剂量呈正相关。SPC组肝组织变性、坏死的程度亦明显减轻 (P <0 .0 0 1,P<0 .0 1,P<0 .0 5 )。结论　SPC对CCl4所致小鼠急性肝损伤具有明显的保护作用 ,高、中、低剂量组间降酶作用呈明显的量效关系。     

Protective Effect of Oral Acetylcysteine against the Hepatorenal Toxicity of Carbon Tetrachloride Potentiated by Ethyl Alcohol

Considering the well-documented protection of acetylcysteine (AC) in hepatotoxicity related to acetaminophen, we studied the preventive potential of AC against mild hepatotoxicity of CCl4, potentiated with ethyl alcohol (ETH) and the role of tissue glutathione. Rats fed a liquid diet with 30% of energy from ETH, had-intraperitoneal CCl4 administered in three injections, at 7-day intervals. AC was ingested at the level for acetaminophen overdose. ETH markedly potentiated the injury induced by CCl4, as evidenced by higher values of serum alanine aminotransferase (ALT), urinary bile acids (BA), serum creatinine, histological score of liver cell necrosis, mortality and by lower body weights and lower liver glutathione, when compared with CCl4 alone. Protective effect of AC consisted of a lesser hepatocytic necrosis, better body weights and higher liver glutathione. We conclude, that AC favorably modifies liver damage induced by CCl4 and potentiated with ETH. There is a preventive role for AC in subjects who combine ETH overuse with exposure to hepatotoxic xenobiotics, whose toxicity is modified by tissue glutathione.     

Hepatoprotective action of prostaglandin A2 analogs under CCl4-induced liver injury in vitro

Aim: The cytoprotective effects of six novel synthetic prostaglandin A(2) analogs against carbon tetrachloride (CCl(4)) as a toxic agent were studied with isolated rat liver hepatocytes in vitro. Results: It was found that hepatocytes treatment with CCl(4) induced: (i) a significant increase of lactic dehydrogenase (LDH) release from cytoplasm; (ii) leakage of glutamate dehydrogenase (GDH) and acid phosphatase from mitochondria and lysosomes, respectively; (iii) 10-fold increase of trien conjugates formation; and (iv) a reduction of free SH-groups by 50%. Prostanoids U-26, U-9 and U-34 decreased cytotoxic index of CCl(4) on average by 1.5-2.0 times and were more effective than PGI(2), the well-known hepatoprotector of prostanoids type. The protective action of the prostanoids was not a cAMP- or Ca(2+)-dependent process. However, prostanoids U-26, U-9 and U-34 normalized intracellular content of SH-groups, reduced trien conjugates formation by 60-80% and strongly prevented enzyme leakage through cellular membranes. They were also able to inhibit CCl(4) effects via decreasing cytochrome P(450)2E1 activity. Conclusion: The results obtained demonstrate that prostanoids provide cytoprotective effects on liver hepatocytes through the prevention of lipid peroxidation of the plasma and the cellular membranes and maintenance of their barrier function.     

丙肝宁对动物实验性肝损伤的保护作用

目的 研究中药复方丙肝宁的保肝作用。方法 采用Ｄ－Ｇａｌ造成大鼠的急性肝损伤模型和ＣＣＩ４所致慢性肝损伤模型。结果 丙肝宁２个剂量组对Ｄ－Ｇａｌ造成大鼠的急性肝损僵模型和ＣＣＩ４所致慢性肝损伤模型的血清酶活性均具有明显的抑制作用（Ｐ〈０．０５,Ｐ〈０．０１）,病理检查结果表明,丙肝宁２个剂量组对Ｄ－Ｇａｌ造成大鼠的急性肝损伤模型和ＣＣＩ４所致慢笥肝损伤模型的肝脏病理形态的改变具有明显的改善作用。结     

紫草大黄合剂对四氯化碳致小鼠急性肝损伤保护作用的观察

目的：观察不同浓度的紫草大黄合剂对四氯化碳（CCl4）致小鼠急性肝损伤的保护作用。方法：采用腹腔注射CCl4致小鼠急性肝损伤为模型，测定高低剂量的紫草大黄合剂对肝损伤ALT、AST值，同时对肝组织进行病理组织检查。结果：高剂量紫草大黄合剂同联苯双酯一样能够明显降低CCl4致小鼠肝损伤血清ALT、AST值升高（P＜0．01），减轻CCl4对肝脏细胞的病理损伤。结论：紫草大黄合剂对CCl4致急性肝损伤具有一定的保护作用。     

中药金三莪对实验性肝纤维化大鼠小肠通透性的影响

目的　观察中药金三莪对实验性肝纤维化大鼠小肠通透性的影响及其作用机制。方法　将大鼠分为A ,B ,C 3组 ,B组和C组采用四氯化碳造模 ,C组于造模第 4周开始灌胃中药金三莪 ,A组和B组灌胃生理盐水 ,共 4周。观察各组大鼠肝功能 ,血清内毒素、D -乳酸、二胺氧化酶 (DAO)及光镜下肝和小肠组织的病理改变。结果　C组大鼠血清ALT及AST值降低 ,肝小叶结构趋于正常 ,纤维间隔变薄 ,血清内毒素、D -乳酸、DAO水平减低 ,与B组比较有显著性差异。结论　中药金三莪能有效保护肠黏膜 ,阻止肠通透性增加 ,可减轻四氯化碳诱导肝纤维化大鼠的肝损伤及纤维化程度。     

鲨肝活性肽S-8300对小鼠急性肝损伤的保护作用

目的：研究鲨肝活性肽S-8300对四氯化碳(CCl4)小鼠肝损伤的保护作用。方法：采用CCl4致小鼠肝损伤，观察肝组织切片；测定生化指标，检测小鼠腹腔注射S-8300后血清谷丙转氨酶(sGPT)、血清谷草转氨酶(sGOT)和乳酸脱氢酶(LDH)活性，肝脏超氧化物歧化酶(SOD)活性与丙二醛(MDA)和谷胱甘肽(GSH)含量。结果：S-8300能明显减轻CCl4所致小鼠急性肝损伤；降低血清GPT、GOT、LDH活性及降低肝组织MDA含量，增加肝组织GSH含量和提高SOD活性。结论：鲨肝活性肽S-8300对急性肝损伤有明显的保护作用。     

富锗金针菇多糖对小鼠肝脏的保护作用

目的：研究富锗金针菇多糖（cFVP）对急性肝损伤小鼠转氨酶活性的影响及对肝脏的保护作用，在此基础上研究其精制品FVP1对cCl4损伤的小鼠原代肝细胞的保护作用。方法：采用0．2％CCl4灌胃造成小鼠急性肝损伤模型，以CFVP和阳性对照联苯双酯灌胃给药，测定血清中谷丙转氨酶（ALT）的活性，并对小鼠肝脏进行切片观察；采用二步分离法制备小鼠原代肝细胞，检测FVP1对CCl4损伤的原代肝细胞ALT活力的影响。结果：CFVP高、中剂量组对CCl4致急性肝损伤小鼠ALT活性的升高具有显著的降低作用，与造模组相比有极显著性差异（P〈0．01）；低剂量组与造模组相比有显著性差异（P〈0．05），CFVP对CCl4致小鼠急性肝损伤有明显的保护作用；FVP1中剂量组、低剂量组可使培养液中的ALT活性明显低于模型组，具有极显著性差异（P〈0．01），即ALT明显减少，说明FVP1对CCl4损伤的原代小鼠肝细胞具有保护作用，结论：富锗金针菇多糖具有保护肝脏细胞，防止肝细胞坏死的作用。     

Expression of muscarinic acetylcholine receptors in hepatocytes from rat fibrotic liver

The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3 ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated. Compared to the normal state, the expression levels of m1, 3, 5 in fibrotic liver tissues or hepatocytes were obviously increased, while m2, 4 decreased. 10 μM pilocarpine or 10 μM acetylcholine could increase the alanine aminotransferase (ALT), hydroxyproline (Hyp), collagen I, III in the hepatocytes, and decreased albumin (ALB). They also changed the expressions of mAchR similarly as the fibrotic hepatocytes and livers. However, atropine could ameliorate the state of fibrotic hepatocytes. These data indicate that mAchR played an important role in the regulation of hepatic fibrosis process. Targeting mAchR would have therapeutic potential for hepatic fibrosis.     

复方芪术汤对四氯化碳致大鼠肝纤维化的影响研究

目的探讨复方芪术汤对四氯化碳(CCl4)致大鼠肝纤维化药效的干预作用。方法Wistar雄性大鼠30只,随机分为正常组10只和四氯化碳处理组(20只),四氯化碳1 ml/kg,每周2次腹腔注射,正常组注射等量的生理盐水。造模的第8周,四氯化碳处理组大鼠随机分为复方芪术汤组和模型组,每组10只。在继续造模的同时,复方芪术汤组给予70千克成人的10倍量灌胃,模型组给予等量的生理盐水灌胃,给药4周。12周末处死全部大鼠,留取肝组织样本和血清,测定谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(ALB)、总胆红素(TBiL)。结果四氯化碳造模12周,模型组血清ALT、AST活性显著升高;ALB含量显著下降。血清TBiL含量显著升高。与模型组相比,复方芪术汤组大鼠血清ALB含量显著升高,血清ALT和AST活性显著降低(P<0.01)。但复方芪术汤对血清TBiL降低不明显。病理组织学显示,模型组假小叶形成,肝脏纤维化程度分级均为2、3级;复方芪术汤干预组肝小叶结构不同程度被破坏,肝脏纤维化程度分级大部分在1、2级。结论复方芪术汤可以显著改善大鼠肝功能,对CCl4引起的慢性肝纤维化大鼠有很好的降低肝纤维化程度的作用。