降糖消脂片对KK-A~y转基因小鼠胰岛素抵抗的影响

发布时间：2018-05-30 23:40

本文选题：降糖消脂片 + KK-Ay小鼠　；参考：《中国中西医结合杂志》2017年03期

【摘要】：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(P0.01)。给药8周后模型组小鼠体重增加(P0.01),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(P0.05,P0.01);且高剂量组RBG降低更明显(P0.01);降糖消脂片高、低剂量组小鼠ISI明显升高(P0.05,P0.01)。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(P0.01);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(P0.05,P0.01)。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(P0.01);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(P0.01),与吡格列酮组比较,差异无统计学意义(P0.05)。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。
[Abstract]:Objective to observe the effect of Jiangtang Xiaozhi tablet on the expression of homeostasis model assessment for insulin resistance index-HOMA-IRI, insulin sensitivity index (ISI), insulin receptor (ins) and insulin receptor (insulin receptor) protein in KK-A~y transgenic mice. Methods KKAy transgenic mice were fed with high fat diet to establish diabetic obese mice model. At the same time, 11 C57 mice of the same age were selected as normal control. A total of 55 KK-A~y mice were randomly divided into two groups: pioglitazone group (n = 11). All the above groups were given intragastric administration of sterilizing water of equal volume in normal control group and model group once a day for 8 weeks. After 8 weeks of administration, body weight was measured and random blood glucose was measured, blood was collected from ocular venous plexus, levels of HOMA-IR and isi were measured, HOMA-IR and ISI were calculated, pancreas was taken for morphological observation, expression of INS and InsR in pancreatic tissue was detected by immunohistochemical method. The protein expression of insulin receptor 尾 -InsR 尾 and insulin receptor substrate 1(insulin receptor substrate 1 / IRS-1 were detected by Western blot assay. Results compared with the normal control group, the mice in each group were obese, blood glucose and blood lipid increased significantly (P 0.01). After 8 weeks of administration, the mice in the model group increased their body weight, their blood sugar and blood lipids were stable at high level, compared with the model group, the levels of TGG ins and HOMA-IR in each dose group of Jiangtang Xiaozhi tablet were significantly lower than those of the model group, and the levels of RBG in the high dose group were significantly lower than those in the control group (P 0.01), and Jiangtang Xiaozhi tablet was higher than that in the high dose group, and the levels of TGG ins and HOMA-IR in each dose group were significantly lower than those in the model group. In low dose group, ISI was significantly increased in P0.05 and P0.01. The results of HE staining showed that in the model group, the islets shrank, the number of islets decreased, the density of islets decreased, the islet cells became compensatory hypertrophy, vacuolar degeneration, and apoptotic cells were found, which showed swelling of cytoplasm and nuclear pyknosis. Jiangtang Xiaozhi tablet was high, the number of islet cells in medium dose group increased obviously, degeneration and apoptosis decreased. The immunohistochemical results showed that compared with the normal control group, the INS and InsR cumulative optical density (IOD) values in the model group were significantly lower than those in the model group, and the values of INS and InsR IOD in the pancreas of the model group were significantly higher than those in the model group, and the results showed that the values of INS and InsR IOD in the pancreas of the model group were significantly higher than those in the model group. Compared with the normal control group, the expression of InsR 尾 and IRS-1 protein in the model group was significantly lower than that in the model group, and the expression level of InsR 尾 and IRS-1 protein in each dose group of Jiangtang Xiaozhi tablet was higher than that in the control group, but there was no significant difference between the model group and pioglitazone group. Conclusion Jiangtang Xiaozhi tablet has obvious effects on reducing glucose, reducing lipid and improving insulin resistance in KK-A~y diabetic obese mice. The mechanism may be to promote the binding of INS and receptor by increasing the expression of InsR 尾 and IRS-1 in islet cells, thereby improving glucose. Lipid metabolism and IR state.
【作者单位】：中国中医科学院西苑医院基础医学研究所中药药理北京市重点实验室;
【基金】：科技部重大新药创制项目(No.2010ZX09102-213,No.2012ZX09103201-040)
【分类号】：R587.1

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