葛根素对2型糖尿病大鼠胰腺β细胞损伤的影响

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摘要目的：探讨葛根素对2型糖尿病大鼠胰腺β细胞损伤的影响及其机制。方法：采用高脂饮食联合小剂量链脲佐菌素腹腔注射建立2型糖尿病大鼠模型，随机分为糖尿病模型组和葛根素（100 mg·kg-1）治疗组，另取正常大鼠作为对照组。腹腔注射给药，正常对照组和糖尿病模型组给予等体积丙二醇，每天1次，连续4周后处死大鼠。测定大鼠空腹血糖、糖化血红蛋白（HbA1c）、血清胰岛素水平和胰腺组织中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性和丙二醛（MDA）含量；实时定量PCR检测胰腺端粒长度；Western blot检测胰腺组织中磷酸化的腺苷酸激活蛋白激酶（p-AMPK）和沉默信息调节因子1（SIRT1）、解偶联蛋白2（UCP2）及凋亡相关蛋白cleaved caspase-3/caspase-3、Bim、Bax、Bcl-2的表达。结果：糖尿病大鼠空腹血糖、HbA1c和胰腺组织MDA含量及UCP2、Bax、Bim、cleaved caspase-3/caspase-3的蛋白表达量均明显高于正常对照组（均P＜0.01），而血清胰岛素水平、胰腺组织SOD、CAT活性和端粒长度及p-AMPK/AMPK、SIRT1、Bcl-2的蛋白表达量均明显低于正常对照组（均P＜0.01）；经葛根素干预后，上述改变逆转，与糖尿病模型组比较差异有统计学意义（均P＜0.01）。结论：葛根素对2型糖尿病大鼠胰腺β细胞有一定的保护作用，其机制可能一方面与减轻氧化应激损伤，保护端粒长度进而抑制β细胞凋亡有关；另一方面与增强SIRT1活性，减少UCP2表达有关。

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关键词 ：葛根素, 糖尿病, 胰腺, 端粒长度, 凋亡, 解偶联蛋白2

Abstract：Objective: To study the effects of puerarin on diabetic pancreatic β-cell injury and to explore its possible mechanisms in type 2 diabetic rats. Methods: A type 2 diabetic rat model was established by the combination of a high-fat diet and a single low-dose streptozocin intraperitoneal injection. The animals were randomly divided into diabetic model group and puerarin (100 mg•kg-1, i.p.) treatment group, with other 8 normal rats as a control group. The rats were treated daily for 4 consecutive weeks, and the equal volume of vehicle (5% propanediol, i.p.) was given to the normal control and diabetic model group. The rats were sacrificed and fasting blood glucose, glycated hemoglobin (HbA1c) and serum insulin levels, as well as malondialdehyde (MDA) content, the activities of superoxide dismutase (SOD) and catalase (CAT) in pancreas were measured. The pancreatic telomere length was determined by real-time quantitative PCR. The protein levels of phosphorylated AMP-activated protein kinase (AMPK), sirtuin1 (SIRT1) and uncoupling protein 2 (UCP2) as well as apoptosis-related proteins, e.g. cleaved caspase-3/caspase-3, Bim, Bax and Bcl-2 in pancreas were assessed by Western blot. Results: The fasting blood glucose, HbA1c, and MDA contents as well as the protein expressions of UCP2, Bax, Bim and cleaved caspase-3/caspase-3 in pancreas of diabetic rats were significantly higher than those in normal controls (P<0.01, respectively). However, insulin level in serum, SOD and CAT activities, telomere length as well as the protein expressions of p-AMPK/AMPK, SIRT1 and Bcl-2 in pancreas of diabetic rats were significantly decreased as compared with those in normal animals (P<0.01, respectively). In contrast, in puerarin treatment group, the above changes were reversed, significant differences of those were found as compared with those in diabetic model group (P<0.01, respectively). Conclusion: Puerarin exerts preventive and remedial effects on the diabetic pancreatic β-cell, which is probably due to protecting telomere length and inhibiting β-cell apoptosis via alleviating oxidative damage, and decreasing UCP2 expression through enhancing SIRT1 activity as well.

Key words： puerarin diabetes mellitus pancreas telomere length apoptosis uncoupling protein 2

收稿日期: 2017-06-08

基金资助:浙江省自然科学基金资助项目（LY13H290007）；温州市科技局公益性科技计划项目（Y20170167）。

作者简介: 陈秀芳（1972-），女，浙江永嘉人，副教授，博士

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I12/859

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