代谢综合征大鼠肠系膜脂肪组织中肾素-血管紧张素系统的变化

Renin-Angiotensin System in Mesenteric Adipose Tissues in Rats with Metabolic Syndrome

目的探讨代谢综合征(MS)大鼠肠系膜脂肪组织中肾素-血管紧张素系统(RAS)变化及拮抗血管紧张素Ⅱ(AngⅡ)对脂肪细胞成脂作用的影响。方法30只8周龄健康雄性Wistar大鼠随机分为MS组和正常对照组,分别给予高脂饲料和普通饲料喂养24周,造成MS模型后,取出肠系膜脂肪组织,应用RT-PCR和Westernblot法检测脂肪组织中mRNA和蛋白质表达。同时,将前脂肪细胞(3T3-L1)进行诱导分化,油红O染色观察脂滴形成情况,比率荧光倒置显微镜检测脂肪细胞内钙水平([Ca2+]i)。给予AngⅡ刺激,并观察血管紧张素Ⅱ受体阻断剂(ARB)坎地沙坦或血管紧张素转换酶抑制剂(ACEI)巯甲丙脯酸对脂滴形成及细胞内钙水平([Ca2+]i)的作用。结果MS大鼠肠系膜脂肪组织的血管紧张素原(AGT)、血管紧张素转换酶(ACE)和血管紧张素Ⅱ受体亚型1(AT1R)表达均显著高于正常对照组(P<0·05,P<0·01);未诱导前脂肪细胞和经AngⅡ处理的成熟脂肪细胞未见明显脂滴形成,给予ACEI和ARB的成熟脂肪细胞有明显的脂滴形成;AngⅡ可致前脂肪细胞内钙水平([Ca2+]i)显著增加(P<0·01),巯甲丙脯酸和坎地沙坦可阻断其效应,而对成熟脂肪细胞,AngⅡ介导的细胞内钙水平([Ca2+]i)升高受到抑制,但坎地沙坦能恢复AngⅡ的效应,巯甲丙脯酸与AngⅡ组比较细胞内钙水平([Ca2+]i)差异无显著性。结论代谢综合征大鼠肠系膜脂肪组织中RAS系统处于激活状态,拮抗RAS能恢复脂肪细胞的基本功能。

Objective To investigate the renin-angiotensin system （BAS） in mesenteric adipose tissues and effect of angiotensin Ⅱ on adipocyte differentiation. Methods Thirty normal 8-week-old male Wistar rats were divided into groups on normal diet and high-fat diet. The rats on high-fat diet for 24 weeks developed the metabolic syndrome respectively. The mRNA and protein expression of mesenteric adipose tissue were measured by reverse transeription-polymerase chain reaction （BT-PCR） and Western blot. Lipid drop in 3T3- L1 preadipocytes and mature adipocytes were observed using oil-red O staining. The fluorescence microscope was used to detect eytosolic-free calcium in 3T3-L1 predipocytes and mature adipoeytes. Results The expressions of angiotensinogen, angiotensin converting enzyme, angiotensin Ⅱ receptor type 1 in mesenterie adipose tissue were significantly increased in rats with metabolic syndrome compared with those in rats on normal diet （P 〈 0. 05, P 〈 0. 01 ）. After administration of angiotensin Ⅱ , no lipid droplet in 3T3-L1 preadipocytes and adipoeytes were observed, however, intensive lipid droplet in adipoeyte was found after administration of captopril and candesartan. Angiotensin Ⅱ increased the intracellular-free calcium concentration in preadipocytes （P 〈0. 01 ）, which was blocked by captopril and candesartan; in contrast, angiotensin Ⅱ effect was blunt in mature adipocyte. Captopril and candesartan partially recovered the angiotensin Ⅱ -mediated increase of cytosolic-free calcium. Conclusion RAS in the mesenteric adipose tissues is active in rats with metabolic syndrome, and antagonization of RAS can recover the lipogenesis of adipocyte.