Li Xin, Yuan Li, Xu Guoling, Qi Cuijuan, Li Jin, Li Hailing, Cheng Suosuo
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2009 Dec;29(6):684-8. doi: 10.1007/s11596-009-0602-6. Epub 2009 Dec 29.
To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). After 8 weeks intervention with perindopril (AE, n=10) or valsartan (AR, n=10), the islet function of the animals was evaluated by intravenous insulin release test (IVIRT). The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor (VEGF) in the islets. The microvessel density (MVD) of islets was detected by counting CD34 positive cells. The hypoxia inducible factor (HIF)-1alpha mRNA expression in the islets was detected by RT-PCR. Compared with normal control group (NC, n=10), the area under the curve for insulin from 0 to 30 min (AUCI(0-30)) of diabetes group (DM, n=8) was decreased by 66.3%; the insulin relative concentration (IRC) of betacell was decreased significantly; the relative content of VEGF was increased obviously [(-4.21+/-0.13) vs (-4.06+/-0.29)]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1alpha mRNA was increased by 1.19 times (all P<0.01). Compared with DM group, the AUCI(0-30) of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1alpha was decreased by 27.2% and 29.0% respectively (all P<0.01 or P<0.05). There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.
为探讨肾素 - 血管紧张素系统阻断对糖尿病大鼠胰岛微血管密度的影响及其与胰岛功能的关系,通过给予高热量实验饲料并腹腔注射小剂量链脲佐菌素(30 mg/kg)建立糖尿病模型。用培哚普利(AE组,n = 10)或缬沙坦(AR组,n = 10)干预8周后,通过静脉胰岛素释放试验(IVIRT)评估动物的胰岛功能。对胰腺进行免疫组织化学染色,分析胰岛中胰岛素和血管内皮生长因子(VEGF)的含量。通过计数CD34阳性细胞检测胰岛微血管密度(MVD)。用RT - PCR检测胰岛中缺氧诱导因子(HIF)-1α mRNA表达。与正常对照组(NC组,n = 10)相比,糖尿病组(DM组,n = 8)0至30分钟胰岛素曲线下面积(AUCI(0 - 30))降低了66.3%;β细胞胰岛素相对浓度(IRC)显著降低;VEGF相对含量明显升高[(-4.21±0.13) vs (-4.06±0.29)];胰岛MVD降低了71.4%;HIF - 1α mRNA相对表达升高了1.19倍(均P<0.01)。与DM组相比,AE组和AR组的AUCI(0 - 30)分别升高了44.6%和34.9%;IRC也显著升高;VEGF相对含量分别降低了21.2%和21.7%;MVD分别升高了62.5%和75.0%;HIF - 1α相对表达分别降低了27.2%和29.0%(均P<0.01或P<0.05)。AE组和AR组上述指标无显著差异。结论:阻断肾素 - 血管紧张素系统(RAS)可能通过增加糖尿病大鼠胰岛的MVD来改善胰岛功能。