化浊解毒方对2型糖尿病胰岛素抵抗大鼠糖脂代谢及肝脏脂素-2表达水平的影响

Effect of Huazhuo Jiedu Decoction on glucose and lipid metabolism and lipin-2 expression in liver of rats with type 2 diabetic insulin resistance

目的探讨化浊解毒方对2型糖尿病胰岛素抵抗大鼠糖脂代谢及肝脏中脂素-2(Lipin-2)表达水平的影响。方法选择健康雄性SD大鼠40只,自适应喂养1周后,随机选择正常喂养的8只SD大鼠作为空白对照组,其余SD大鼠以高脂饲料联合链脲佐菌素(STZ)诱导2型糖尿病胰岛素抵抗模型。将造模成功的大鼠随机分为模型组、化浊解毒方低剂量组、化浊解毒方中剂量组、化浊解毒方高剂量组,每组8只。化浊解毒方低、中、高剂量组分别给予化浊解毒颗粒生药1.5 g/(kg·d)、3.0 g/(kg·d)、6.0 g/(kg·d)灌胃,空白对照组和模型组给予同体积的生理盐水灌胃,均持续4周。灌胃结束后,取各组大鼠空腹血检测血糖(FPG)、三酰甘油(TG)、总胆固醇(TC)、胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感性指数(HOMA-ISI);处死大鼠,采用Western blot法检测各组大鼠肝脏组织中Lipin-2蛋白相对表达量,采用HE染色法观察肝脏组织形态学变化。结果模型组FPG、TG、TC、FINS、HOMA-IR及肝脏组织中Lipin-2蛋白相对表达量均明显高于空白对照组(P均<0.05),HOMA-ISI明显低于空白对照组(P<0.05);化浊解毒方各组FPG、TG、TC、FINS、HOMA-IR及肝脏组织中Lipin-2蛋白相对表达量均明显低于模型组(P均<0.05),HOMA-ISI均明显高于模型组(P均<0.05)。化浊解毒方各组肝组织病理改变较模型组改善明显,且中、高剂量组改善更明显。结论化浊解毒方能显著改善2型糖尿病大鼠胰岛素抵抗状态和糖脂代谢异常,机制可能与降低肝脏中Lipin-2表达有关。

Objective It is to study the effects of Huazhuo Jiedu Decoction on glucose and lipid metabolism and lipin-2 expression in liver of rats with type 2 diabetic insulin resistance.Methods Forty healthy male SD rats were selected.After adaptive feeding for 1 week,8 normal-fed SD rats were randomly selected as the blank control group.The remaining SD rats were given high-fat diet combined with streptozotocin(STZ)to establish type 2 diabetes insulin resistance models.The successfully modeled rats were randomly divided into a model group,a low-dose group of Huazhuo Jiedu Decoction,a medium-dose Huazhuo Jiedu Decoction group,and a high-dose Huazhuo Jiedu Decoction group,with 8 rats in each group.The low,medium and high dose groups of Huazhuo Jiedu Decoction were given 1.5 g/(kg·d),3.0 g/(kg·d),6.0 g/(kg·d)crude drug of Huazhuo Jiedu granules,and the blank control group was given the same volume of normal saline by gavage,all the groups were treated for 4 weeks.At the end of the gavage,the fasting blood of the rats in each group was taken to determine fasting plasma glucose(FPG),triacylglycerol(TG),total cholesterol(TC),insulin(FINS),and calculate the insulin resistance index(HOMA-IR)and insulin sensitivity index(HOMA-ISI);after than the rats were sacrificed,and the relative expression of Lipin-2 protein in the liver tissue of each group was detected by Western blot,and the morphological changes of liver tissue were observed by HE staining.Results The levels of FPG,TG,TC,FINS,HOMA-IR and relative expression of Lipin-2 protein in liver tissue in the model group were significantly higher than those in the blank control group(all P<0.05),and HOMA-ISI was significantly lower than that in the blank control group(P<0.05);the levels of FPG,TG,TC,FINS,HOMA-IR and relative expression of Lipin-2 protein in liver tissue in every Huazhuo Jiedu Decoction group were significantly lower than those in the model group(all P<0.05),and HOMA-ISI was significantly higher than that in the model group(P<0.05)The pathological changes of liver tissue in each group of Huazhuo Jiedu Decoction were significantly improved compared with the model group,and the improvement was more obvious in the middle and high-dose groups.Conclusion Huazhuo Jiedu Decoction can significantly improve insulin resistance and glucose-lipid metabolism in type 2 diabetic rats,and the mechanism may be related to the reduction of Lipin-2 expression in liver.