血管紧张素系统阻断对糖尿病大鼠胰岛功能的影响。
Effects of renin-angiotensin system blockade on islet function in diabetic rats.
机构信息
Department of Endocrinology, Union Hospital, Tongji Medical College of HuaZhong Science & Technology University, 1277 Jiefang Road, Wuhan City, China.
出版信息
J Endocrinol Invest. 2010 Jan;33(1):13-9. doi: 10.1007/BF03346544.
AIMS
To investigate the effects of renin-angiotensin system (RAS) blockade on islet structure and function in diabetic rats, and its mechanisms.
METHODS
Diabetic rat models were created by high-fat high-caloric laboratory chow plus small dose (30 mg/kg) streptozotocin ip injection. After 8-week intervention with perindopril (AE, no.=10) or valsartan (AR, no.=10), all the animals' islet function was evaluated by iv glucose tolerance test. Pancreases were stained by immunohistochemistry technique to qualitative and/or quantitative analysis the content of insulin, inducible nitric oxide synthase (iNOS), transforming growth factors-beta1 (TGF-beta1) in islets. The apoptosis of islet cells was detected by transferase-mediated dUTP nick-end labeling dUTP nick end labeling (TUNEL). The expression level of angiotensinogen (AGT) and insulin mRNA in islets were detected by RT-PCR.
RESULTS
Compared with normal control group (NC, no.=10), area under the curve of insulin from 0 to 10 min (AUCI0-10) of diabetes group (DM, no.=8) was decreased by 66.9%, the relative expression of local AGT was increased by 69.2%, the insulin relative concentration (IRC) of beta-cell and the expression of insulin mRNA were decreased significantly, the amount of apoptotic cells in unit islet area was increased by 2.1 times, the relative content of iNOS and TGF-beta1 positive cell relative volume (TRV) was increased by 23.0% and 2.52 times, respectively (all p<0.01). Compared with DM group, AUCI0-10 of AE and AR group was increased by 41.4% and 33.2%, respectively; the relative expression of local AGT was decreased by 21.4% and 23.4%, respectively; IRC and the expression of insulin mRNA were increased significantly; the amount of apoptotic islet cells was decreased by 79.0% and 36.2%, respectively; the relative content of iNOS was decreased by 16.5% and 18.9%, respectively; TRV was decreased by 43.8% and 35.6%, respectively (all p<0.01). There were no significant differences between group AE and AR.
CONCLUSION
Blockade of RAS may improve diabetic rats islet function via the amelioration of intra-islets oxidative stress, fibrosis and apoptosis.
目的
探讨肾素-血管紧张素系统（RAS）阻断对糖尿病大鼠胰岛结构和功能的影响及其机制。
方法
采用高脂高糖饲料加小剂量（30mg/kg）链脲佐菌素腹腔注射建立糖尿病大鼠模型。用培哚普利（AE，n=10）或缬沙坦（AR，n=10）干预 8 周后，通过静脉葡萄糖耐量试验评估所有动物的胰岛功能。用免疫组织化学技术对胰岛进行染色，定性和/或定量分析胰岛素、诱导型一氧化氮合酶（iNOS）、转化生长因子-β1（TGF-β1）在胰岛中的含量。用末端转移酶介导的 dUTP 缺口末端标记法（TUNEL）检测胰岛细胞凋亡。用 RT-PCR 检测胰岛血管紧张素原（AGT）和胰岛素 mRNA 的表达水平。
结果
与正常对照组（NC，n=10）相比，糖尿病组（DM，n=8）0 至 10 分钟时胰岛素曲线下面积（AUCI0-10）减少 66.9%，局部 AGT 的相对表达增加 69.2%，β细胞胰岛素相对浓度（IRC）和胰岛素 mRNA 表达明显降低，单位胰岛面积凋亡细胞数增加 2.1 倍，iNOS 阳性细胞相对体积（TRV）和 TGF-β1 相对含量分别增加 23.0%和 2.52 倍（均 P<0.01）。与 DM 组相比，AE 组和 AR 组的 AUCI0-10 分别增加 41.4%和 33.2%，局部 AGT 的相对表达分别降低 21.4%和 23.4%，IRC 和胰岛素 mRNA 表达明显增加，胰岛细胞凋亡数分别减少 79.0%和 36.2%，iNOS 相对含量分别降低 16.5%和 18.9%，TRV 分别降低 43.8%和 35.6%（均 P<0.01）。AE 组和 AR 组之间无显著差异。
结论
RAS 阻断可通过改善胰岛内氧化应激、纤维化和细胞凋亡来改善糖尿病大鼠的胰岛功能。
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