皮质抑素抑制内质网应激减轻大鼠主动脉钙化

Cortistatin alleviates aortic calcification in rats by inhibiting endoplasmic reticulum stress

目的观察皮质抑素(cortistatin,CST)对大鼠动脉钙化的作用并探讨其可能的分子机制。方法大鼠快速钙化模型采用腹腔注射大量维生素D3制备,血浆钙水平和动脉组织钙含量均采用钙试剂盒检测,动脉组织钙化性病理变化和蛋白表达分别采用茜素红S染色和Western blot方法检测。结果与对照组比较,VD组大鼠血浆钙水平、动脉的钙含量和骨钙素(osteocalcin,OCN)蛋白表达均显著升高(均为P<0.05),茜素红S染色发现动脉组织中膜紊乱,沿弹力纤维分布大量染色阳性的红/橘色颗粒。VD+CST组与单纯VD组相比较,连续皮下注射40μg/(kg·d)CST能够明显降低大鼠血钙水平(P<0.05)、动脉钙含量(P<0.01)和OCN蛋白表达水平(P<0.05),也减轻中膜的弹力纤维紊乱和茜素红S染色阳性颗粒。进一步的Western blot结果发现VD组CHOP和GRP94蛋白表达较对照组显著升高(二者均P<0.05),而CST能够使CHOP和GRP94蛋白表达较VD组显著降低(P<0.01和P<0.05)。结论 CST能够降低维生素D3所致的大鼠主动脉组织的钙沉积和OCN蛋白表达,这可能与其抑制内质网应激和降低血浆钙水平有关。

Objective To investigate effect of cortistatin(CST)on aortic calcification and its possible molecular mechanism in rat rapid aorta calcification induced by the administration of vitamin D3.Methods Rapid aorta calcification model was established in rats by the injection of vitamin D3.Plasma calcium level and aortic calcium content were determined by Calcium Assay Kits.The pathological calcification changes and protein expressions in aortic tissues was detected by Alizarin Red S staining and Western blot,respectively.Results Plasma calcium level,calcium content and OCN protein expression of aortic tissues in VD group were obviously increased than those in control group(all P<0.05).Compared with the control group,Alizarin Red S staining indicated tunica media disorder and many scattered red/orange particles among the elastic laminas in VD group.Continuous subcutaneous injection of CST with 40μg/(kg·d)dramatically decreased calcium level(P<0.05),calcium content(P<0.01)and OCN protein expression(P<0.05)in VD+CST group than VD group alone.Moreover,CST also reduced the number of positive particles stained by Alizarin Red S.Western blot detection further revealed that protein expressions of CHOP and GRP94 were markedly up-regulated in VD group compare with control group.Compared with VD group alone(both P<0.05),CST significantly down-regulated the protein expressions of CHOP(P<0.01)and GRP94(P<0.05)in rat aortic tissues of VD+CST group.Conclusion CST could reduce the calcium deposition and OCN protein expression in aortic tissues of rats,which was probably mediated by its suppression of endoplasmic reticulum stress and reduction of plasma calcium level.