肝糖异方及其拆方对CCl4-HF复合模型诱导的肝源性糖尿病大鼠肝纤维化及糖代谢异常的影响  

Effects of Gantang Yifang and its disassembled prescriptions on liver fibrosis and abnormal glucose metabolism in hepatogenic diabetic rats induced by CCl-HF

作　　者：顾宏图[1] 杨亚田 徐虹[2] 许笑阳 平键[1] 徐列明[1] 赵长青[1] GU Hongtu;YANG Yatian;XU Hong;XU Xiaoyang;PING Jian;XU Lieming;ZHAO Changqing(Liver Cirrhosis Department,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201103,China;Department of Gastroenterology and Hepatology,Hangzhou Red Cross Hospital,Hangzhou 310003,Zhejiang China)

机构地区：[1]上海中医药大学附属曙光医院肝硬化科,上海201103 [2]浙江省杭州市红十字会医院消化肝病科,浙江杭州310003

出　　处：《上海中医药杂志》2020年第7期86-93,共8页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81673780,81102707)。

摘　　要：目的观察肝糖异方及其拆方扶正化瘀方、实脾方对CCl4所致肝硬化大鼠肝纤维化及糖代谢异常的影响。方法 98只SPF级Wistar大鼠随机分为正常组、模型组、肝糖异方组、实脾方组、扶正化瘀方(FZHY)组和二甲双胍组。除正常组外,其余各组均采用40%CCl4橄榄油溶液皮下注射+复合高脂饮食造模。自造模的第5周开始,用药组分别按体质量灌胃给药,每天1次,连续8周。12周时,OGTT试验检测大鼠糖耐量,比较各组血糖AUC和血清胰岛素水平,并计算胰岛素抵抗指数HOMA-IR。记录大鼠体质量、肝质量、脾质量,计算肝体比、脾体比;收集血清和组织样本,检测血清ALT、AST、Alb、TBiL水平;肝组织切片HE染色观察肝脂肪变性,天狼猩红染色观察肝脏胶原沉积情况;比色法测定肝组织中羟脯氨酸(Hyp)含量。结果与模型组比较,肝糖异方和扶正化瘀方可明显改善糖耐量异常,降低血糖AUC(P<0.05),明显降低HOMA-IR(P<0.05,P<0.01);实脾方组空腹胰岛素浓度明显降低(P<0.05)。血清生化检测结果显示肝糖异方和实脾方可以降低ALT(P<0.05)水平,实脾方可以降低AST(P<0.05)水平。HE染色结果显示,肝糖异方明显减轻肝细胞脂肪变性;天狼猩红染色结果表明,肝糖异方和扶正化瘀方可明显降低肝脏胶原面积(P<0.01)以及肝组织Hyp含量(P<0.05,P<0.01)。结论肝糖异方及其拆方扶正化瘀方、实脾方可通过减轻肝脂肪变性及纤维化,调节改善糖耐量异常及胰岛素抵抗,从而缓解CCl4联合高脂饮食所致大鼠肝源性糖尿病。Objective To observe the effects of Gantang Yifang(GTYF) and its disassembled prescriptions—Fuzheng Huayu(FZHY)recipe and Shipi(spleen-firming) recipe on liver fibrosis and abnormal glucose metabolism in cirrhotic rats induced by CCl4. Methods A total of 98 SPF Wistar rats were randomly divided into 6 groups including normal group,model group,GTYF group,Shipi group,FZHY group and metformin group. All rats except the rats in the normal group were modelled by subcutaneous injection of 40%CCl4 olive oil solution combined with high-fat diet. From the fifth week of modeling, the rats in medication groups were given intragastric administration according to body mass once a day for 8 weeks. At 12 weeks, the glucose tolerance of rats was measured by OGTT test;the levels of blood glucose AUC and serum insulin were compared;and the insulin resistance index(HOMA-IR) was calculated. The body mass, liver mass and spleen mass of the rats were recorded, and the liver-to-body ratio and spleen-to-body ratio were calculated. Serum and tissue samples were collected to detect the levels of serum ALT, AST, Alb and TBiL. Liver steatosis was observed by HE staining, collagen deposition by Sirius red staining,and the content of hydroxyproline(Hyp) in liver tissue determined by colorimetry. Results Compared with the model group,GTYF and FZHY recipe could significantly improve the abnormal glucose tolerance,reduce the blood glucose AUC(P<0.05) and HOMA-IR(P<0.05),and the fasting insulin concentration in the Shipi recipe group was significantly lower than that in the model group(P<0.05). The results of serum biochemical test showed that GTYF and Shipi recipe could reduce the level of ALT(P<0.05) and Shipi recipe could also reduce the level of AST(P<0.05). The results of HE staining showed that GTYF could significantly reduce the steatosis of hepatocytes,and Sirius red staining showed that GTYF and FZHY recipe could significantly reduce the collagen area of the liver and the content of Hyp in liver tissue(P<0.05,P<0.01). Conclusion GTYF a

关 键 词：肝糖异方 糖耐量异常 胰岛素抵抗 肝纤维化 糖代谢异常 肝源性糖尿病 大鼠 

分 类 号：R285.5[医药卫生—中药学]