玉郎伞黄酮对四氯化碳诱导的大鼠肝纤维化的影响

Effect of Yulangsan Flavonoids on Liver Fibrosis Induced by Carbon Tetrachloride in Rats

目的:研究玉郎伞黄酮(YLSF)对四氯化碳(carbon tetrachloride,CCl4)所致大鼠肝纤维化的治疗作用,并探讨其作用机制。方法:将SD大鼠随机分成模型组及空白对照组(NC),模型组以50%CCl4食用油溶液为诱导剂ig造模,NC组以生理盐水ig。将病理检查确认形成肝纤维化的SD大鼠,随机分成模型对照组(MC)和药物干预组。药物干预组分别以YLSF(20,40,80 mg.kg-1)及秋水仙碱片(0.20 mg.kg-1)ig;MC组以等剂量生理盐水ig。末次给药24 h后处死大鼠,采集血清及肝组织,检测大鼠血清中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)活性,测定肝组织中超氧化物岐化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)和谷胱甘肽过氧化酶(GSH-Px),并观察肝组织病理学改变。结果:YLSF(20,40,80 mg.kg-1)各剂量组大鼠血清中AST和ALT分别为(207.85±101.72),(131.55±35.09),(129.98±37.21)U.L-1和(90.51±44.24),(47.79±16.11),(44.56±16.31)U.L-1;YLSF各剂量组大鼠肝组织中SOD,MDA,GSH-Px,GSH含量分别为(143.14±42.82),(146.53±31.98),(147.41±32.82)U.mg-1,(2.57±0.54),(2.19±0.57),(2.11±0.59)nmol.mg-1,(463.55±271.07),(659.14±162.23),(752.08±200.70)nmol.mg-1,(5.06±1.09),(6.10±0.97),(6.89±0.98)nmol.mg-1。各剂量YLSF和阳性药能显著降低大鼠血清中AST(P<0.01)及肝组织MDA含量(P<0.05或P<0.01),并显著提高肝组织中SOD含量(P<0.05或P<0.01);中、高剂量YLSF和阳性药可降低大鼠血清中ALT水平(P<0.01),显著升高大鼠肝组织GSH含量(P<0.01);中、高剂量YLSF能显著升高大鼠肝组织GSH-Px(P<0.01)。各剂量YLSF及阳性药均能够减轻肝细胞损伤程度(P<0.05或P<0.01)。结论:玉郎伞黄酮对CCl4诱导的大鼠具有一定治疗作用,其机制可能与其清除自由基、抑制脂质过氧化有关系。

Objective：The aim of our study is to investigate the effect of Yulangsan flavonoids（YLSF） against CCl4-induced liver fibrosis in rats and study its mechanism.Method：The SD rats were divided into two groups randomly：hepatic fibrosis group and normal control group（NC）.The rats of hepatic fibrosis group were induced by intragastric administration（ig） of 50% CCl4,and rats in NC group were given normal saline（NS）.The rats of hepatic fibrosis group confirmed by the pathological inspection were divided into 2 groups randomly：Drug intervention group and the model group which were treated with NS.The drug intervention group was divided randomly into 3 different does YLSF groups（20,40,80 mg · kg-1） and a positive control group（colchicine tablets 0.20 mg · kg-1）.All rats were treated with drugs or NS for four consecutive weeks ig,one time a day.Twenty-four hours after the last administration of drugs,all rats were sacrificed,and the blood serum and hepatic tissue were taken quickly.The activities of alanine transaminase（ALT） and aspartale transaminase（AST） in the serum and the levels of superoxide dismutase（SOD）,malonaldehyde（MDA）,glutathione（GSH）,and glutathione synthesis（GSH-Px） in hepatic tissue were analyzed,and the degree of hepatic injury was examined.Result：The content of AST,ALT in serum of each YLSF groups’ rats were（207.85±101.72）,（131.55±35.09）,（129.98±37.21） U · L-1,（90.51±44.24）,（47.79±16.11）,（44.56±16.31） U · L-1;and the content of SOD,MDA,GSH-Px,GSH in the tissue of each YLSF groups’ rats were（143.14±42.82）,（146.53±31.98）,（147.41±32.82） U · mg-1,（2.57±0.54）,（2.19±0.57）,（2.11±0.59） nmol · mg-1,（463.55±271.07）,（659.14±162.23）,（752.08±200.70） nmol · mg-1,（5.06±1.09）,（6.10±0.97）,（6.89±0.98） nmol · mg-1.Compared with the model control group,the increased activity of AST in serum and the increased content of MDA in liver induced by CCl4 were decreased significantly,and the decreased levels of SOD in liver was increased significantly in all dose of YLSF groups and positive control group.The activity of ALT in serum was decreased significantly（P〈0.01） and the content of GSH（P〈0.01） in liver was increased in the high dose and the middle dose of YLSF groups and positive control group.Meanwhile the activity of GSH-Px in the liver was increased significantly in the high dose and the middle dose of YLSF groups（P〈0.01）.The degree of hepatic injury in all dose of YLSF groups and positive control group could be lessened（P〈0.05 or P〈0.01）.Conclusion：Our findings demonstrate that YLSF has a certain curative effect on CCl4-induced liver fibrosis in rats,and its mechanism maybe involve in attenuating free radical and inhibiting the lipid peroxidation.