芪茵颗粒对非酒精性脂肪性肝病大鼠胰岛素抵抗和CYP2E1表达的影响

Effect of Qiyin granules on insulin resistance and CYP2E1 expression in rats with nonalcoholic fatty liver disease

目的观察芪茵颗粒对非酒精性脂肪性肝病(NAFLD)大鼠模型胰岛素抵抗(IR)和肝细胞色素酶CYP2E1表达的影响,探讨芪茵颗粒治疗NAFLD的作用机制。方法将72只雄性SD大鼠随机分为空白组、模型组、芪茵颗粒低剂量组、芪茵颗粒中剂量组、芪茵颗粒高剂量组和硫普罗宁组,每组12只。除空白组常规饲养、自由进食水外,其余组均采用高脂乳剂给大鼠灌胃,每日1次,共10周。模型复制成功后,各给药组给予相应药物灌胃,空白组和模型组灌胃等体积蒸馏水,每日1次,共10周。检测各组大鼠血清TC、TG、ALT、AST、空腹血糖和空腹胰岛素水平,计算胰岛素抵抗指数(HOME-IR);称大鼠体质量,计算肝指数;光镜下观察肝脏病理组织学变化,计算肝脏NAS积分;免疫组化法检测各组大鼠肝组织中CYP2E1的阳性表达细胞数。结果实验结束后,芪茵颗粒中剂量组和高剂量组体质量均明显低于模型组(P均<0.05);模型组肝指数及血清TC、ALT、AST水平和HOME-IR均明显高于空白组(P均<0.05),各给药组肝指数及血清ALT和AST水平均明显低于模型组(P均<0.05),芪茵颗粒高剂量组、芪茵颗粒中剂量组及硫普罗宁组HOMEIR均明显低于模型组(P均<0.05)。模型组肝脏NAS积分和CYP2E1阳性表达率均明显高于空白组(P均<0.05),各给药组肝脏NAS积分和CYP2E1阳性表达率均明显低于模型组(P均<0.05);芪茵颗粒中剂量组和高剂量组肝脏NAS积分均明显低于芪茵颗粒低剂量组(P均<0.05),且芪茵颗粒中剂量组明显低于硫普罗宁组(P<0.05);芪茵颗粒中剂量组和高剂量组CYP2E1阳性表达率均明显低于芪茵颗粒低剂量组和硫普罗宁组(P均<0.05)。结论芪茵颗粒可以控制NAFLD大鼠体质量增长,降低肝脏转氨酶水平、肝指数及肝细胞CYP2E1的表达,改善肝组织脂肪变性及IR,从而发挥治疗NAFLD的作用。

Objective It is to observe the influence of Qiyin granule on insulin resistance（IR） and hepatic cytochrome CYP2E1 expression in rat model of nonalcoholic fatty liver disease（NAFLD）,and to explore the mechanism of Qiyin granule in the treatment of NAFLD. Methods 72 male SD rats were randomly divided into blank group,model group,low,medium,high dose Qiyin group and tiopronin group,12 rats in each group. In addition to the control group of conventionalfarming and free eating and drinking,the others were treated by high fat emulsion to rats by gavage,once a day,for a total of 10 weeks.After the models were successfully established,the animals were given the corresponding drugs in each group respectively,once a day,for a totle of 10 weeks. The levels of serum TC,TG,ALT,AST,fasting plasma glucose（FPG） and fasting insulin levels were detected,and the insulin resistance index（HOME-IR） were calculated; the body weight of the rats was weighed,then the liver index was calculated; the histopathological changes of liver were observed under light microscope,and the liver NAS score was calculated; the positive expression of CYP2E1 in liver tissue of rat was detected by immunohistochemistry. Results At the end of the experiment,the body weight of the middle and high dose Qiyin group were significantly lower than that of the model group（all P〈0. 05）; The liver index,and serum levels of TC,ALT,AST,and HOME-IR in the model group were significantly higher than those in the blank group（all P〈0. 05）,the liver index and serum ALT,AST levels in each administration group were significantly lower than those in the model group（all P〈0. 05）,the HOME-IR of the middle and high dose Qiyin group and tiopronin group were significantly lower than those of the model group（all P〈0. 05）. The liver NAS score and positive rate of CYP2E1 in the model group was significantly higher than that in the blank group（all P〈0. 05）,but the liver NAS score and positive rates of CYP2E1 in each administration group were significantly lower than those in the model group（all P〈0. 05）; the liver NAS score in the middle and high dose Qiyin group was significantly lower than that in the low dose Qiyin group（P〈0. 05）,and the middle dose Qiyin group was significantly lower than the tiopronin group（P〈0. 05）; The positive expression rates of CYP2E1 in the middle and high dose Qiyin group were significantly lower than those in the low dose Qiyin group and tiopronin group（all P〈0. 05）. Conclusion Qiyin granule can control the growth of body weight of NAFLD rats,reduce the level of hepatic transaminase,liver index and the expression of CYP2E1 in hepatocytes,and improve the fatty degeneration of liver tissue and IR,so as to play a role in the treatment of NAFLD.