摘要
目的探讨阿利吉仑对脱氧皮质酮诱导的大鼠心肌纤维化的影响及其相关机制。方法将45只SD大鼠行右肾切除,术后予1%氯化钠饮水4周并随机分为3组:对照(A)组、脱氧皮质酮(B)组、脱氧皮质酮+阿利吉仑(C)组。颈动脉插管测大鼠平均动脉血压(MABP),大鼠心脏组织经天狼猩红染色测定心肌间质胶原容积分数(CVF)和心肌血管周围胶原面积比(PVCA)的表达,Western blot法测定细胞外信号调节激酶1/2(ERK1/2)、磷酸化细胞外信号调节激酶(pERK1/2)和基质金属蛋白酶9(MMP9)的含量,免疫放射检测血浆及心肌组织的肾素活性(RA)及血管紧张素Ⅱ(AngⅡ)的含量。结果与A、C组比较,B组的MABP水平和CVF、PVCA的表达以及心肌组织中ERK1/2、pERK1/2、MMP9的含量显著升高(P<0.05);与A组比较,B组及C组血浆及心肌组织中的RA、AngⅡ的含量显著减低(P<0.05);与B比较,C组心肌纤维化程度和心肌组织中的ERK1/2、pERK1/2、MMP9、RA、AngⅡ的含量明显减少(P<0.05),而血浆中的RA、AngⅡ的含量和MABP水平减少不明显。结论阿利吉仑能改善脱氧皮质酮诱导的心肌纤维化,其机制可能与抑制心肌局部肾素-血管紧张素-醛固酮系统、减少AngⅡ生成及ERK1/2途径的传导和MMP9的表达有关。
Objective To investigate the effects and mechanisms of aliskiren on myocardial fibrosis induced by desoxycorticosterone acetate-salt in rats.Methods Forty-five SD rats which were uninephrectomized were limited to drink 1% NaCl water for 4 weeks and assigned to the follow groups：vehicle control rats（A group）,desoxycorti-costerone acetate-salt treated rats（B group）,aliskiren＋desoxycorticosterone acetate treated rats（C group）.Blood pressure were measured with catheterization.Collagen volume fraction（CVF）and perivascular collagen area（PVCA）were analyed by Sirius red staining.MMP9,ERK1/2,pERK1/2 were detected by Western blot.RA and AngⅡ were detected by radiommoassay（RIA）.Results Compared with B group,MABP of C group and A group were elevated,and significant difference was observed（P〈0.05）,but mean arterial blood pressure of C group was not decreased significantly.Myocardial fibrosis was observed in B group.Compared with the other two groups,the index of CVF and PVCA were increased significantly（P〈0.05）.Compared with C group,the levels of MMP9,ERK1/2,pERK1/2,local tissue RA and Ang Ⅱ were significantly increased in B group（P〈0.05）,but RA and Ang Ⅱ in plasma were no significantly decreased.Conclusion Aliskiren may attenuate myocardial fibrosis induced by desoxycorticosterone acetate-salt independent of blood.Local tissue generation of Ang Ⅱ may be responsible for the results.
出处
《安徽医科大学学报》
CAS
北大核心
2011年第5期427-430,共4页
Acta Universitatis Medicinalis Anhui
