目的观察降糖消脂片对KK-A~y转基因小鼠稳态模型评估胰岛素抵抗指数(homeostasis model assessment for insulin resistance index,HOMA-IR)、胰岛素敏感指数(insulin sensitivity index,ISI)、胰腺组织胰岛素(insulin,INS)及胰岛素受体(insulin receptor,InsR)蛋白表达的影响。方法采用高脂饲料喂养KKAy转基因小鼠,制备糖尿病肥胖小鼠模型。同时选取11只同龄C57小鼠作为正常对照。将成模的55只KK-A~y小鼠采用随机数字表法分为模型组、吡格列酮组(8 mg/kg)、降糖消脂片高、中、低剂量组(分别给予降糖消脂片10、5、2.5 g生药/kg),每组11只。以上各组均灌胃给药,正常对照组及模型组灌胃等体积灭菌水,每日1次,连续8周。给药8周后,称体重并测随机血糖(random blood glucose,RBG);眼静脉丛取血,测定INS、TC及TG水平,计算HOMA-IR及ISI;取胰腺进行形态学观察;采用免疫组化方法检测胰腺组织INS及InsR表达;采用免疫印迹(Western blot)法检测胰腺胰岛素受体β(insulin receptorβ,InsRβ)及胰岛素受体底物1(insulin receptor substrate 1,IRS-1)蛋白表达水平。结果与正常对照组比较,造模后各组小鼠出现肥胖,血糖及血脂明显升高(P<0.01)。给药8周后模型组小鼠体重增加(P<0.01),血糖及血脂稳定在高位水平;与模型组比较,降糖消脂片各剂量组小鼠体重、TG、INS及HOMA-IR水平明显降低(P<0.05,P<0.01);且高剂量组RBG降低更明显(P<0.01);降糖消脂片高、低剂量组小鼠ISI明显升高(P<0.05,P<0.01)。胰腺病理HE染色结果显示,模型组胰岛萎缩,胰岛数目明显减少,分布稀疏,胰岛密度减低,胰岛细胞代偿性肥大,空泡变性,并可见凋亡细胞,表现为胞浆肿胀,核固缩。降糖消脂片高、中剂量组胰岛细胞数目明显增多,变性及凋亡细胞减少。免疫组化结果显示,与正常对照组比较,模型组INS及InsR累积光密度(IOD)值明显降低(P<0.01);与模型组比较,降糖消脂片各剂量组胰腺INS及InsR IOD值明显增加(P<0.05,P<0.01)。Western blot结果显示,与正常对照组比较,模型组InsRβ及IRS-1蛋白表达明显降低(P<0.01);与模型组比较,降糖消脂片各剂量组InsRβ及IRS-1蛋白表达水平升高(P<0.01),与吡格列酮组比较,差异无统计学意义(P>0.05)。结论降糖消脂片对KK-A~y糖尿病肥胖小鼠有明显的降糖、降脂及改善胰岛素抵抗的作用,其机理可能是通过增加胰岛细胞InsRβ及IRS-1表达,促进INS与受体的结合,从而改善糖、脂代谢和IR状态。 Objective To observe the effects of Jiangtang Xiaozhi tablet on homeostasis model assessment of insulin resistance index (HOMA-IR), insulin sensitivity index (ISI), pancreatic tissue Insulin (INS) and insulin receptor (InsR) protein expression. Methods KKAy transgenic mice were fed with high-fat diet to prepare diabetic mice model. At the same time select 11 same-age C57 mice as normal control. Fifty-five KK-A-y mice were randomly divided into model group, pioglitazone group (8 mg / kg), hypoglycemic and Xiaofu Tablet high, medium and low dose groups Tablets 10,5,2.5 g crude drug / kg), each group of 11. The above groups were intragastric administration, normal control group and model group intragastric administration of equal volume of sterile water once a day for 8 weeks. Eight weeks after administration, weighed and measured random blood glucose (RBG); ophthalmic venous plexus blood, INS, TC and TG levels were measured, HOMA-IR and ISI were calculated; morphological observation of the pancreas was performed; The expression of INS and InsR in pancreatic tissue was detected by histochemical method. The protein expression of insulin receptor β (InsRβ) and insulin receptor substrate 1 (IRS-1) in pancreas was detected by Western blot. Level. Results Compared with the normal control group, the mice in each group developed obesity, blood glucose and blood lipids were significantly increased (P <0.01). Compared with model group, body weight, TG, INS and HOMA-IR levels of mice in each dose of Jiangtang Xiaozhi Tablet were significantly increased (P <0.01), blood glucose and blood lipids were stable at high level (P <0.05, P <0.01), and RBG decreased more significantly in high dose group (P <0.01); ISI of high and low dose Jiangtang Xiaozhi tablets increased significantly (P <0.05, P <0.01) ). Pancreatic pathology HE staining showed that the model group, pancreatic islet atrophy, the number of islets was significantly reduced, sparsely distributed, islet density was reduced, islet cells compensatory hypertrophy, vacuolar degeneration, and apoptotic cells, showing cytoplasmic swelling, nuclear pyknosis . Hypoglycemic Xiaozhi tablet high and medium dose groups was significantly increased the number of islet cells, degeneration and decreased apoptotic cells. The results of immunohistochemistry showed that the values ​​of IOD of INS and InsR in model group were significantly lower than those in normal control group (P <0.01). Compared with model group, the levels of INS and InsR IOD in each dose group Value increased significantly (P <0.05, P <0.01). Western blot results showed that compared with the normal control group, the expression of InsRβ and IRS-1 in the model group was significantly decreased (P <0.01); Compared with the model group, the expression levels of InsRβ and IRS-1 (P <0.01). Compared with pioglitazone group, the difference was not statistically significant (P> 0.05). Conclusion Jiangtang Xiaozhi Tablet has obvious hypoglycemic, hypolipidemic and insulin-resistant effects on diabetic KK-A-y diabetic mice. The mechanism may be that it can promote the expression of InsRβ and IRS-1 by increasing islet cells Body to improve sugar, lipid metabolism and IR status.