血管紧张素Ⅱ受体拮抗剂对大鼠脂肪分泌瘦素、脂联素和TNF-α的影响

Angiotensin Ⅱ AT1 receptor blockade modulates leptin,adiponectin and TNF-α in rat

目的探讨血管紧张素Ⅱ受体拮抗剂Candesartan对大鼠脂肪合成瘦素、脂联素、TNF-α等脂肪细胞因子的影响。方法20只雄性WistarKyoto大鼠分为对照组和治疗组,分别予以口服安慰剂和Candesartan(10mg·kg-1·d-1),监测摄食量和体重变化。17周后处死大鼠,收集附睾和肾周围脂肪组织并称重,分离脂肪细胞并测定直径;测定血浆生化、胰岛素、瘦素、脂联素和TNF-α;通过RT-PCR测定附睾脂肪瘦素、脂联素和TNF-αmRNA基因表达。结果治疗组大鼠体重和体内脂肪含量均较对照组减低;附睾脂肪细胞缩小;两组间血糖和胰岛素无显著差异。治疗组血浆瘦素水平和脂肪组织瘦素mRNA表达均降低,而血浆脂联素和脂肪组织脂联素mRNA表达增加。两组血浆TNF-α水平低于可测范围,治疗组脂肪TNF-αmRNA表达下降。结论血管紧张素Ⅱ受体拮抗剂降低大鼠脂肪瘦素和TNF-α的合成和分泌,增加脂联素的合成和分泌。

Objective To investigate the effects of angiotensin Ⅱ AT1 receptor antagonist-Candesartan on production of leptin, adiponectin and TNF-α in rat. Methods 20 male Wistar Kyoto rats were randomly divided into vehicle and Candesartan treated groups. The dosage of Candesartan was 10mg · kg^-1· d^-1. Food intake and bodyweight were recorded each week. Rats were sacrificed by decapitation after 17 weeks. Epididymal and perirenal fat were collected and weighted. Adipocytes were isolated from epididymal adipose tissue with collagenase. Diameter of adipocyte was evaluated. Blood chemistry, insulin, leptin, adiponectin and TNF-α were assayed, mRNA expressions of leptin, adiponectin and TNF-α of epididymal adipose tissue were assayed with RT-PCR. Results In Candesartan treated group, bodyweight and content of adipose tissue were significantly decreased, and adipocytes shrunk. Blood glucose and insulin levels showed no difference between two groups. Plasma leptin level and leptin mRNA expression in adipose tissue were lower, and plasma adiponectin level as well as adiponectin mRNA expression were higher in Candesartan treated group. Plasma TNF-α level was too low to detect with super sensitive kit, and mRNA expression of TNF-α was decreased in Candesartan treated group. Conclusions Angiotensin Ⅱ AT1 receptor antagonist decreases the production of leptin and TNF-α, enhances synthesis as well as release of adiponectin in rat adipose tissue.