Urantide降低动脉粥样硬化大鼠胸主动脉中p38 MAPK表达

Urantide reduces p38 MAPK expression in thoracic aorta of rats with atherosclerosis

目的探讨尾加压素拮抗剂urantide对动脉粥样硬化(AS)大鼠胸主动脉中p38丝裂原活化蛋白激酶(p38MAPK)基因和蛋白的影响。方法180只Wistar大鼠分为:正常组(NC)、模型组(AS)[采用腹腔注射维生素D3(VD3)并联合高脂饲料喂养的方法建立AS大鼠模型]、辛伐他汀组(灌胃给予辛伐他汀5μg/kg)、urantide3、7、14d组(尾静脉注射urantide30μg/kg)。给药结束后,HE染色大鼠胸主动脉;免疫组织化学染色、RT-qPCR以及Westernblot检测大鼠胸主动脉中p38MAPKmRNA和蛋白表达。结果AS组大鼠胸主动脉出现典型的AS病理改变,urantide使胸主动脉AS病变明显减轻。AS组大鼠胸主动脉中p38MAPK阳性表达以及基因和蛋白水平与NC组相比显著升高(P<0.01);Urantide各给药组大鼠胸主动脉中p38MAPK阳性表达以及基因和蛋白水平与AS组相比显著降低(P<0.01)。结论Urantide可通过抑制p38的表达而起到保护胸主动脉,防治AS的作用。

Objective To investigate the effect of urotensin antagonist,urantide on the expression of p38 mitogen activated protein kinase genes and proteins in atherosclerotic rats thoracic aorta.Methods One hundred and eighty wistar rats were randomly divided into normal group,model group,positive drug group,urantide 3 d group,urantide 7 d group and urantide 14 d group.The model group was established by injecting the loading dose of vitamin D 3 and feeding a high-fat diet.The morphological changes of thoracic aorta were detected by HE staining.The expression of p38 mitogen activated protein kinase genes and proteins in rat thoracic aorta was detected by immunohistochemistry,RT-qPCR and Western blot.Results Typical AS pathological changes occurred in the thoracic aorta of rats in the AS group,and urantide significantly reduced the pathological changes of the thoracic aorta.The expression of p38 MAPK and the gene and protein levels in the thoracic aorta of the AS group were significantly higher than those in the NC group(P<0.01).The positive expression of p38 MAPK and genes and proteins in the thoracic aorta of the rats in the urantide group was significantly lower than that of the AS group(P<0.01).Conclusions Urantide can improve the function of thoracic aorta by inhibiting the expression of p38 mitogen activated protein kinase to achieve the purpose of treatment of AS.