ACEI改善糖尿病大鼠的糖代谢紊乱  

ACEI ameliorates glycometabolism in diabetic rats

作　　者：黄艳[1] 袁莉[2] 郭彩红[2] 刘晓玲[2] 

机构地区：[1]湖北省天门市第一人民医院内分泌科,431700 [2]华中科技大学同济医学院附属协和医院内分泌科,武汉430022

出　　处：《国际内分泌代谢杂志》2009年第6期385-388,404,共5页International Journal of Endocrinology and Metabolism

基　　金：湖北省自然科学基金资助项目（2005ABA158）

摘　　要：目的利用血管紧张素转换酶抑制剂（ACEI）阻断肾素-血管紧张素系统（RAS），研究阻断RAS改善胰岛素抵抗及糖代谢的作用机制，探讨脂肪组织局部RAS与胰岛素抵抗的关系。方法30只雄性Wistar大鼠随机分为正常对照组（NC组）、高脂组（HF组）和高脂干预组（AE组），分别以基础饲料喂养、高脂喂养、高脂加培哚普利[4mg／（kg·d）]干预喂养12周。干预结束后HF组和AE组给予链脲佐菌素（STZ）20mg／kg小剂量腹腔注射诱导成模，2周后3组大鼠分别行口服葡萄糖耐量试验（OGTY）及计算稳态模型评估-胰岛素抵抗指数（HOMA-IR），评价胰岛素抵抗和糖代谢，处死大鼠，以RT—PCR法检测附睾和肾周脂肪组织脂联素、抵抗素、纤溶酶原激活物抑制剂（PAI）-1mRNA的表达。结果与NC组（n=10）比较，HF组（n=7）大鼠OGTF各时点血糖、血糖曲线下面积（AUC）、HOMA—IR显著升高，PAI-1、抵抗素mRNA表达显著增加，分别是NC组的1．50倍、1．47倍，脂联素mRNA的表达下降了40．8％（均P〈0．01）；与HF组比较，AE组（n=9）大鼠OGTF各时点血糖有所下降，60、120min血糖差异有显著性（P〈0．05），AUC、HOMA—IR显著减少，PAI—1、抵抗素mRNA表达较HF组分别下降了28％、38．1％，脂联素mRNA表达升高为HF组的1．62倍（P均〈0．05）。结论ACEI可以改善长期高脂喂养联合STZ诱导大鼠的胰岛素抵抗和糖代谢紊乱，其作用机制可能与改善内脏脂肪组织的脂肪因子表达相关。Objective To investigate the amelioration of blocking renin-angiotensin system （RAS） on insulin resistance, glucose metabolism with angiotensin converting enzyme inhibitor （ACEI） and its mechanism. Investigate the correlation of RAS in adipose tissue region and insulin resistance. Methods 30 male Wistar rats were randomly devided into normol control group （NC）, high-fat diet group （HF）, high-fat diet and intervention group （AE） which were intervened with perindopril 4 mg/（ kg·d） for 12 weeks. Then, HF and AE were performed intraperitoneal injection of a small dose （20 mg/kg）of streptozotocin （STZ）. After 2 weeks, insulin resistance and glucose metabolism were assessed by OGTT and HOMA-IR for 3 groups. Then adipocytes were islated from epididymal and perirenal adipose tissue for mRNA expressions of PAI-1, resistin and adiponectin with reverse transcription-polymerase chain reaction （RT-PCR）. Results Compared with NC （n = 10） , area under curve （AUC） of blood glucose and every time-point blood glucose of OGTT were higher, HOMA-IR index was higher,the level of PAI-1 and resistin mRNA expression were higher,while the level of adiponectin mRNA expression were lower in HF group （ n = 7 ） （ P 〈 0. 01 ）. Compared with HF, AUC of blood glucose and every time-point blood glucose of OGTT were lower, HOMA-IR index was lower, the level of PAI-1 and resistin mRNA expression were lower, and the level of adiponectin mRNA expression were higher in AE （ P 〈 0.05 ）. Conclusion ACET can alleviate insulin resistance and glycometabolism and may modulate mRNA expression of adipocytokines in rats fed with long-term high-fat diet and induced with streptozotocin.

关 键 词：ACEI 内脏脂肪 脂联素 抵抗素 PAI-1 

分 类 号：R587.1[医药卫生—内分泌] R972.4[医药卫生—内科学]