调脂护肝方干预高脂饲养大鼠脂肪肝的实验研究

Experimental Research on Tiaozhi Hugan Decoction Treatment on Rat Fatty Livers Induced by High Fatty Diet

目的:观察调脂护肝方对高脂饲食脂肪肝大鼠的干预效应,探讨其药效学机制。方法:将雄性SD大鼠64只正常喂养1周后,随机分为正常组12只,饲基础饲料,实验组52只,给予高脂饲料饲食(含胆固醇2%,猪油10%,基础饲料88%),13周末随机抽取正常组2只,高脂饲养大鼠8只,验证高脂饲养大鼠脂肪肝形成。剩余实验组44只随机分为4组即病理模型组、东宝甘泰组、羊栖菜组、调脂护肝方组,每组均为11只,在继续饲高脂饲料外,分别给予东宝甘泰,按0.5g/(kg.d)(用蒸馏水配成0.05g/mL的混悬液),羊栖菜煎剂按10mL/(kg.d)(10mL含羊栖菜生药20g),调脂护肝方按10mL/(kg.d)(由羊栖菜、丹参、制大黄、葛根、泽泻、茯苓=3∶2∶1∶1∶1∶1其中10mL含羊栖菜20g),共8周。第21周末称重,处死动物,取肝脏,计算肝脂数(肝重/体重×100%)观察肝脏组织的病理学变化,抽血,并检测以下指标:血清总胆固醇(TC)、甘油三酯(TG)、血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、血清超氧化物歧化酶(SOD)、丙二醛(MDA)、空腹血糖(FBG)、空腹胰岛素(FINS)并计算胰岛素抵抗指数(HOMA-IR)、肝TG含量。结果:①与病理模型组、东宝甘泰组比较羊栖菜组与调脂护肝方组大鼠体重及肝指数均较低(二者均为P<0.01)。②与病理模型组、东宝甘泰组、羊栖菜组比较,调脂护肝方组血清TC值较低(P<0.01)。③与病理模型组、东宝甘泰组比较,羊栖菜组、调脂护肝方组血清、肝脏TG均降低(P<0.01)④与正常组、病理模型组、东宝甘泰组、羊栖菜组比较,调脂护肝方组HLD-C增高(P<0.01)。⑤与病理模型组、东宝甘泰组、羊栖菜组比较调脂护肝方组、正常组血清ALT、AST值均较低(P<0.01)。⑥与病理模型组、东宝甘泰组、羊栖菜组比较,调脂护肝方组MDA值较低(P<0.01),SOD值较高(P<0.01)。⑦与病理模型组、东宝甘泰组比较,调脂护肝方组HOMA-R I值减低(P<0.01)。⑧与病理模型组、东宝甘泰组比较,调脂护肝方肝脂变率较低(P<0.05),肝组织炎症活动度也较低(P<0.01)。结论:调脂护肝方治疗非酒精性脂肪肝的药效机制为:①降低体重与肝指数。②调整脂质代谢:降低血清和肝脏甘油三酯、总胆固醇。③改善肝功能:降低ALT、AST。④抗脂质过氧化,提高抗氧化酶活性。⑤改善胰岛素抵抗。⑥减轻肝脂肪变性与肝组织炎症。

Objective ： Observe theraputic effect of Tiaozhi Hugan decoction and investigate its pharmcodynamics. Methods：64 SD male rats were fed a normal diet for one week then they were randomly divided into two groups ,one was norreal group which were 12 rats fed normal diet, the other,which were 52 rats fed high fatty diet for 12 weeks. At the end of 13th weed,8 rats,2 rats were fed normal,6 rats were fed high fat diet,were searified to test fatty liver model . Then 44 rats,whlch were fed high fatty diet,were randomly divided into 4 groups of eleven each： model control group, DongBao GanTai group, seaweed decoction group and Tiaozhi Hugan decoction group. They were fed high fatty diet continuously for 8 weeks. At the same time model control group rats were given distilled water 10mL/（ kg·d）by gastmlavage , seaweed decoction group rats were fed seaweed decoction 20g/（ kg·d）. Dongbao Gantai group rats were fed Dong Bao Gantai, 0. 5g/（kg·d） ,Tiaozhi Hugan decoction group were fed Tiaozhi Hugan decoction 10mL/（ kg·d） （contained seaweed 20g/kg）. At the end of 21th week, all rats were scarified, body weight, liver index （ liver/body weight ratio） serum ALT, AST,TG,TC,MDA,SOD,fasting blood glucose,fasting insulin and liver TG were assayed,the liver histology changes of all rats were observed also. Results： （ 1 ） Compared with model control group and DongBao Gantai group, the level of body weight,liver index in seaweed group and Tiaozhi Hugan decoction group were lower significantly （P 〈 0. 01 ）. （2）The level of TC in Tiaozhi Hugan decoction group was lower than that in model control group, Dongbao Gantai group, seaweed decoction group（ P 〈 0. 01 ） and higher than that in normal GrouP（ P 〈 0.05 ）. （ 3 ） Compaired with model control and Dongbao Gantai group,the level of TG in serum and liver in seaweed group and Tiaozhi Hugan group was lower（ P 〈 0. 01 ）. （4） The level of HLD - C in Tiaozhi Hugan group was high than that in normal group, model control group, Dongbao Gantai group, seaweed decoction group（ P 〈 0.01 ）. （5）The level of ALT,AST in model control group, Dongbao Gantai group and seaweed decoction group was higher than that in normal group and Tiaozhi Hugan decoction group. （6）Compared wth model Control Group, Dongbao Gantai group, seaweed decoction group, the level of MDA in Tiaozhi Hugan decoction was lower significantly（P 〈0.01 ）,the level of SOD was higher significantly（ P 〈 0. 01 ）. （7） The level of HOMA -IR in Tiaozi Hugan group was lower than that in model control, Dongbao Gantai group （P 〈 0.01 ）. （8） The pathologic change of livers showed that Tiaozhi Hugan decoction has better effect on anti-fatty liver and improving lipid hepatitis than Dong-Bao GanTai decoction. Concluzon ： It was suggestion that the pharmacodynamics and therapeutic function of Tiaozhi Hugan Decoction to fatty liver induced by high fatty diet were ： （ 1 ） Lowering body weight and liver index. （2） Adjusting lipome-tabolism： reducing TC （ in serum） TG （ in serum and liver）. （ 3 ） Improving liver function-lowering ALT and AST. （4） Anti-lipid Peroxide - increasing SOD and Lowing MDA in serum. （5） Anti-insulin resistance. （6） Improving lipidic aggradation and inflammation in liver.