苯丙氨酸二肽类化合物Y101对CCl4诱导大鼠慢性肝损伤的保护作用

Effect of the phenylalanine dipeptide compound Y101 on carbon tetrachloride-induced chronic liver injury in rats

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 determine the preventing effect of Y101, a phenylalanine dipeptide compound, on CCL4-induced chronic liver injury in rats, and to explore the possible mechanism. Methods： Chronic liver injury was induced by CCl4 ＋ phenobarbital in rats. Y101 at 17.5, 35 and 70 mg· kg^-1 or Fufang Biejia Ruangan Pian （540 nag. kg^-1, positive control） were administered. Rats were killed at 7 weeks after treatment. Blood was collected to detect serum activities of ALT, AST and ALP, and serum contents of ALB and TP. The liver was isolated and weighed; the contents of HyP, MDA, NO, SOD and GSH in the liver were determined. In addition, the liver histopathology was examined. The weights of spleen and thymus were also analyzed. Results： Compared with the normal rats, the rats with liver injury exhibited increased serum activities of ALT, AST and ALP, liver contents of HyP, MDA and NO, and the thymus index （P 〈 0.01 ）. The serum contents of ALB and TP, liver contents of SOD and GSH, and the indexes of liver and spleen were significantly decreased （P 〈 0.01 ） after liver injury. Y101 at 17.5, 35 and 70 mg·kg^-1 attenuated these changes in rats with chronic liver injury in a dose-dependent manner. Y101 at 35 and 70 mg·kg^-1 significantly improved the liver histopathological changes as well. Conclusion： Y101 attenuates CC14-induced chronic liver injury, especially in reducing liver enzyme activities. Its effect may be relevant to inhibition of increased HyP, reduction in MDA and NO, and increase in SOD and GSH.