RAS阻断剂对人前脂肪细胞分化和胰岛素敏感性的影响  

Effects of RAS blockers on differentiation and insulin sensitivity of human preadipocytes

作　　者：田凤石[1] 雒熔[1] 葛进[1] 赵志强[1] 吴岩[1] 班东杰[2] 

机构地区：[1]天津市公安医院内科,300042 [2]天津市公安医院外科,300042

出　　处：《国际内分泌代谢杂志》2009年第1期43-46,共4页International Journal of Endocrinology and Metabolism

基　　金：天津市自然科学基金资助项目（07JCYBJC11000）

摘　　要：目的探讨肾素-血管紧张素系统（RAS）阻断剂对体外原代培养的人内脏和外周来源的前脂肪细胞分化和胰岛素敏感性的影响。方法自16例行电切开腹部手术的健康成年女性腹部皮下和网膜分离前脂肪细胞。分为4组，即无干预的正常对照（NC）组、噻唑烷二酮类药物吡格列酮（Pioglitazone）组、血管紧张素转换酶抑制剂（ACEI）类药物贝那普利（Benazapril）组和血管紧张素Ⅱ受体拈抗剂（ARB）类药物替米沙坦（Telmisartan）组，诱导分化共14d。观察细胞活力、细胞内脂质含量和前脂肪细胞分化标志物——甘油-3-磷酸脱氖酶的活性。细胞的胰岛素敏感性通过葡萄糖消耗试验测定。结果对照组皮下来源的前脂肪细胞活力高于网膜，脂质含量反而低于网膜来源细胞，二者胰岛素敏感性无差别。与对照组相比。贝那普利、替米沙坦和毗格列酮均能明显提高网膜和皮下来源前脂肪细胞的细胞活力和脂质含量，并提高细胞的胰岛素敏感性；其中，替米沙坦组网膜前脂肪细胞的上述各指标均高于吡格列酮组。在网膜，替米沙坦和吡格列酮组的葡萄糖消耗量分别为（5．567±1．612）mmol／L和（4．418±1．572）mmol／L，P=0．020；皮下则相反，两组葡萄糖消耗量分别为（5．335±1．461）mmoL／L和（7．506±1．615）mmol／L，P〈0．01。结论RAS阻断剂（替米沙坦和贝那普利）可促进人前脂肪细胞分化并改善细胞的胰岛素敏感性，且较之吡格列酮在内脏发挥优势性作用。Objective To study the effects of renin-angiotensin system （RAS） blockers on differentiation and insulin sensitivity of human omental and subcutaneous preadipocytes. Methods Human omental and subcutaneous preadipocytes were isolated from abdominal adipose tissue obtained from 16 healthy adult women undergoing elective abdominal surgery. Preadipocytes were differentiated for 14 days without any treatment （ Group NC） or in the presence of either angiotensin converting enzyme inhibitor Benazapril, angiotensin Ⅱ receptor blocker Telmisartan or thiazolidinedione Pioglitazone in serum-free medium. Cell activition, lipid content and glycerol-3-phosphate dehydrogenase （G3PDH） activition of preadipocytes were observed during the differentiation. The amount of glucose consumption was employed to determine the insulin sensitivity of preadipocytes. Results Cell activition, measured by MTT assay, was higher in differentiated subcutaneous preadipocytes than that in omental preadipocytes under basal culture condition （ Group NC）, while the lipid content of subcutaneous preadipocytes was lower than that of omental ones. There is no difference of insulin sensitivity between subcutaneous and omental preadipocytes in group NC. Most of the metabolic and differentiating parameters were improved significantly by the treament of Benazapril, Telmisartan or Pioglitazone. Furthermore,Telmisartan seemed to be superior to Pioglitazone in inducing differentiation of omental preadipocytes. The G3PDH activition of subcutaneous preadipocytes could only be stimulated by Pioglitazone, and the effects of Telmisartan on G3PDH activition were omental depot-specific. These findings were consistent with the effects of RAS blockers on insulin sensitivity of preadipocytes. The improvement of glucose consumption was significantly greater in Tehnisartan-treated human omental preadipocytes compared with Pioglitazone-treated ones[ （5. 567 ± 1. 612） mmol/L vs. （4. 418 ±1. 572） mmol/L, P = 0. 020]. In contrary, it was lower in Tehn

关 键 词：肾素-血管紧张素系统阻断剂 噻唑烷二酮类药物 前脂肪细胞 细胞分化 胰岛素抵抗 

分 类 号：R656[医药卫生—外科学]