脂联素拮抗血管紧张素Ⅱ诱导系膜细胞细胞外基质产生

Adiponectin antagonizes angiotensin H -induced extracelluar matrix production of human renal mesangial cells

目的观察脂联素对血管紧张素Ⅱ（AngⅡ）诱导人。肾小球系膜细胞（MC）表达转化生长因子β1（TGF-β1）及纤连蛋白（FN）的影响，并探讨其信号通路。方法用RT0PCR和间接免疫荧光法对MC表达脂联素受体进行检测；用实时定量PCR和酶联免疫吸附法检测脂联素对AngⅡ诱导MC表达TGF—β1及FN的影响；用Western印迹法测定p-AMPK／AMPK比值。结果（1）MC能表达脂联素受体1和2。（2）10mg／L脂联素可明显抑制AngⅡ诱导MC高表达TGF-β1及FN（均P〈0．05）。（3）10mg／L脂联素可活化MC的AMPK信号通路。（4）40μmol／L Compound C（AMPK阻断剂）可明显减弱脂联素对AngⅡ诱导MC高表达TGF-β1及FN的拮抗作用（均P〈0．05）。结论脂联素可通过活化AMPK对AngⅡ诱导MC高表达TGF一β1及FN发挥抑制作用。

Objective To investigate the effects of adiponectin on angiotensin H-induced extracellular matrix production of mesangial ceils （MCs） and its possible signaling pathway. Methods RT-PCR and indirect immunofluorescence examination were performed to detect the adiponectin receptors in MCs. Quantitative real-time PCR and enzyme-linked immunosorbent assay （ELISA） were used to observe the effects of adiponectin on angiotensin H-induced transforming growth factor β1 （TGF-β1） and fibronectin production of MCs. Western blotting was used to measure the ratio of p-AMPK to total AMPK. Results （1）Adiponectin receptors 1 and 2 were found in MCs. （2）The up-regulated mRNA and protein expression of TGF-β1 and fibronectin in MCs induced with 10-7 mol/L angiotensin Ⅱ （Ang Ⅱ ） was significantly inhibited by 10 mg/L adiponectin （P〈O.05）. （3）The p-AMPK/AMPK ratio was significantly increased after incubation with adiponectin for 15 min and 30 min （vs 0 min, P〈0.05）, which suggested that adiponectin could activate the AMPK signaling pathway in MCs. The activation of AMPK signaling pathway was blocked by 40 μmol/L compound C, a specific inhibitor of AMPK. （4）The inhibitory effects of adiponectin on angiotensin H-upregulated TGF-β1 and fibronectin expression in MCs were significantly relieved by 40 μmol/L compound C （P〈0.05）. Conclusions There are adiponectin receptors 1 and 2 in MCs. Adiponectin has inhibitory effects on the angiotensin Ⅱ-upregulated TGF-β1 and fibronectin expression in MCs. AMPK signaling pathway may play an important role in the effects of adiponectin above-mentioned.