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为探讨雌激素相关受体α(ERRα)的特异性反向激动剂XCT790对大鼠血管平滑肌细胞(VSMCs)增殖的影响及相关分子信号传导机制,采用原代培养大鼠胸主动脉VSMCs,以胎牛血清(FBS)刺激VSMCs增殖,分别加入不同浓度的XCT790,以CCK-8试剂检测XCT790对VSMCs增殖的影响;以RT-PCR考察ERRα、PGC-1α、OPN和MCAD的mRNA表达水平;以Western blotting检测ERRα、ERK2及p-ERK1/2蛋白表达水平;以ELISA法检测VEGF蛋白水平。结果显示,XCT790对VSMCs增殖的抑制作用在5~20μmol·L-1剂量范围内呈显著剂量依赖性,在10~20μmol·L-1剂量范围内呈显著时间依赖性;且5~20μmol·L-1 XCT790能明显下调ERRα与p-ERK1/2水平(P<0.05,P<0.01)。提示:XCT790可通过下调ERRα及其靶基因转录,进而抑制ERK途径来抑制大鼠VSMCs增殖。
To investigate the effect of specific reverse agonist XCT790 of estrogen-associated receptor α (ERRα) on the proliferation of rat vascular smooth muscle cells (VSMCs) and the related molecular signaling mechanisms, primary cultured rat VSMCs Fetal bovine serum (FBS) stimulated the proliferation of VSMCs, respectively. Different concentrations of XCT790 were added to detect the effect of XCT790 on the proliferation of VSMCs by CCK-8 reagent. The mRNA expression levels of ERRα, PGC-1α, OPN and MCAD were detected by RT- The protein levels of ERRα, ERK2 and p-ERK1 / 2 were detected by Western blotting. The protein expression of VEGF was detected by ELISA. The results showed that the inhibitory effect of XCT790 on proliferation of VSMCs was significantly dose-dependent in the dose range of 5 ~ 20μmol·L-1, and was significantly time-dependent in the range of 10 ~ 20μmol·L-1 dose; and the concentration of 5 ~ 20μmol·L -1 XCT790 significantly decreased the levels of ERRα and p-ERK1 / 2 (P <0.05, P <0.01). Tip: XCT790 can inhibit the proliferation of rat VSMCs by down-regulating ERRα and its target gene transcription, thereby inhibiting the ERK pathway.