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目的:观察苯丙氨酸二肽类化合物Y101对CC l4诱导大鼠慢性肝损伤的保肝作用,探讨其作用机制。方法:CC l4加苯巴比妥诱导大鼠慢性肝损伤,实验分正常组、模型组、Y101低、中、高剂量组(17.5,35,70 m.gkg-1),阳性对照组(鳖甲软肝片,540 m.gkg-1),分别进行防治和给药,7周疗程结束后处死大鼠,检测其血清中谷丙转氨酶(ALT),谷草转氨酶(AST),碱性磷酸酶(ALP)的活性及白蛋白(ALB),总蛋白(TP)含量。取肝脏,称重,检测肝脏中羟脯氨酸(HyP),丙二醛(MDA),一氧化氮(NO),超氧化物歧化酶(SOD),谷胱甘肽(GSH)的含量;另取肝脏做病理组织学检查,取脾、胸腺,称重,将所得数据进行统计分析。结果:与正常组比较,模型组大鼠血清中ALT,AST,ALP活性,肝内HyP,MDA,NO含量及胸腺重量显著升高(P<0.01),血清中ALB,TP含量,肝内SOD,GSH水平及肝脾重量明显降低(P<0.01)。低、中、高剂量Y101对慢性肝损伤大鼠上述指标均有不同程度的改变,且呈良好的剂量关系。给予Y101治疗后,中、高剂量组的肝组织病理变化均明显轻于模型组。结论:Y101对CC l4所致慢性肝损伤具有较好的防治作用,保肝降酶效果明显,其机制可能与抑制HyP增多,降低MDA,NO和升高SOD,GSH有关。
Objective: To observe the hepatoprotective effect of phenylalanine dipeptide compound Y101 on CC l4-induced chronic liver injury in rats and its mechanism. Methods: CC l4 plus phenobarbital induced chronic liver injury in rats. The experiment was divided into normal group, model group, Y101 low, medium and high dose groups (17.5, 35, 70 m.gkg-1), positive control group A soft liver tablet, 540 m.gkg-1), respectively, for prevention and treatment, after 7 weeks of treatment, rats were sacrificed, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase ALP) activity and albumin (ALB), total protein (TP) content. The liver was weighed and the content of hydroxyproline (HyP), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD) and glutathione (GSH) Another liver pathological examination, take the spleen, thymus, weighing, the resulting data for statistical analysis. Results: Compared with the normal group, the activities of ALT, AST, ALP, the content of HyP, MDA, NO in the liver and thymus in the model group were significantly increased (P <0.01) , GSH level and liver and spleen weight decreased significantly (P <0.01). Low, medium and high doses of Y101 in rats with chronic liver injury have varying degrees of the above indicators, and showed a good dose relationship. After treatment with Y101, the histopathological changes in the middle and high dose groups were significantly lighter than those in the model group. CONCLUSION: Y101 has a good preventive and therapeutic effect on chronic liver injury induced by CC l4, and the effect of reducing liver enzymes is obvious. The mechanism may be related to the inhibition of the increase of HyP, the decrease of MDA, the increase of NO and the increase of SOD and GSH.