正肝汤对肝源性糖尿病大鼠胰岛素抵抗及脂肪-胰岛素轴的影响

Effect of Zheng Gan Decoction on Insulin Resistance and Fatty-Insulin Axis in Hepatogenous Diabetes Rats

目的:探讨正肝汤对肝源性糖尿病大鼠胰岛素抵抗及脂肪-胰岛素轴的干预作用。方法:清洁级雄性SD大鼠100只,按体质量随机平均分5组,正常组、模型组及低、中、高剂量组。采用四氯化碳酒精复合法12周制备肝硬化模型,自第12周起,治疗组予不同剂量正肝汤提取液灌胃,模型组予等剂量生理盐水灌胃,连续4周。第16周末处死全部大鼠,检测大鼠肝脏组织形态学、血糖、胰岛素,计算胰岛素抵抗指数;应用Real-time PCR技术检测脂肪-胰岛素轴信号通路中关键基因脂联素、肿瘤坏死因子mRNA变化。结果:模型组可见明确肝硬化征象,与模型组比较,治疗组肝纤维化明显减轻,纤维间隔变细,肝细胞大小、形态接近正常,仅有少量空泡和气球样变,仅见少量炎症细胞浸润。与模型组比较,治疗组的血糖浓度降低,较模型组下降约32%(P<0.05);治疗组胰岛素浓度下降,与模型组比较有统计学意义;胰岛素抵抗指数较模型组下降60%(P<0.05)。模型组血脂联素表达下降、肿瘤坏死因子上升表达;治疗组血脂联素表达上升,肿瘤坏死因子表达下降,有统计学差异(P<0.05)。结论:正肝汤可以改善肝源性糖尿病大鼠血糖及胰岛素抵抗的进行性发展,其机制可能与调控脂肪-胰岛素轴,提高脂联素分泌,降低肿瘤坏死因子表达有关。

Objective： To investigate the intervention effect and potential mechanism of Zheng gan Decoction on fat-insulin-axis of the Hepatogenous diabetes rats. Methods： 100 male SD rats of clean grade were randomly divided into normal group,model group and low,medium,high dose group. The cirrhosis model group was established by alcohol and carbon tetrachloride for 12 weeks. The intervention group was treated by intragastric administration with Zheng gan Decoction as well as the model group was treated by intragastric administration with saline for 4 weeks. Rat tissue morphology,blood glucose and insulin were detected for insulin resistance index calculating. The key adiponectin genes and tumor necrosis factor mRNA on the fat-insulin-axis was assayed by real-time PCR. Results： The histomorphology of liver cirrhosis is obvious in the model group. But the liver fibrosis was reduced,fibrous septum becomes thinning,the form of liver-cell was normal with little vacuoles and ballooning degeneration and inflammatory cell infiltration in the intervention group. Compared with the model group,the blood glucose concentration was decreased by about 32%（ P〈0. 05） as well as the insulin concentration,the difference is statistically significant. And the insulin resistance index was decreased by60%（ P〈0. 05）. The expression of adiponectin was decreased in the model group with the tumor necrosis factor increasing. There were conversely results in the intervention group so that the difference is statistically significant（ P〈0. 05）.Conclusion： Zheng gan decoction can improve blood glucose and insulin resistance of Hepatogenous diabetes rats,which due to the regulation on fat-insulin-axis associated with the elevating secretion of adiponectin as well as the reducingexpression of tumor necrosis factor.