目的 探讨替米沙坦阻断肾素-血管紧张素系统对db/db小鼠胰岛内微血管结构的影响。方法 将22只8周龄db/db小鼠随机分为2组:替米沙坦组11只和安慰剂组11只;另选11只同周龄db/m小鼠为非糖尿病组。每周监测小鼠体重、血糖,6周后行腹腔葡萄糖耐量试验(IPGTT)并取胰腺行免疫组织化学检测,分析胰岛内微血管中CD31表达情况。结果 治疗6周后,与安慰剂组比较,替米沙坦组小鼠空腹血糖明显降低,胰岛素敏感指数明显升高,差异有统计学意义(P<0.05);非糖尿病组小鼠的体重和空腹血糖明显降低,差异有统计学意义(P〈0.05)。替米沙坦组小鼠葡萄糖曲线下面积明显下降,0~30 min胰岛素曲线下面积明显上升,差异有统计学意义(P〈0.05);替米沙坦组小鼠胰岛中血管内皮细胞CD31染色强度明显增强,血管数量明显增加。结论 替米沙坦阻断血管紧张素Ⅱ1型受体能够改善胰岛微环境,增加胰岛内微血管数量,促进早期相胰岛素分泌,从而保护胰岛β细胞。
Objective To explore the effects of telmisartan on intraislet microvasculature in db/db mice through blocking reninangiotensin system.Methods Twenty-two 8 weeks old db/db mice were randomized to telmisartan group(5 mg/kg telmisartan,n=11) and placebo group(n=11),the drugs were given via gavage for 6 weeks.Other 11 agematched db/m mice were concurrently treated with placebo as nondiabetic controls.Body weight and blood glucose were measured every week.After 6 weeks’ treatment,intraperitoneal glucose tolerance test was performed,immunohistochemical examination of pancreas was carried out to analyze expression of CD31 in microvessels of islet.Results After six weeks’ telmisartan treatment,the fasting blood glucose significantly decreased,insulin sensitivity index significantly increased(P〈0.05).AUC of glucose curve decreased(P〈0.05) and AUC of 0-30 min insulin curve increased(P〈0.05) in telmisartan group compared with placebo group.Telmisartan treatment greatly increased staining intensity of CD31 in islets.Conclusions Telmisartan treatment remarkably increased intraislet microvasculature volume,and improved earlyphase insulin secretion,thus protected βcell function.