摘要
目的:评价依达拉奉抑制大鼠压力超负荷致心肌重构形成与血管紧张素Ⅱ1型受体(AT1R)/丝裂原活化蛋白激酶(MAPKs)/类固醇合成急性调节蛋白(StAR)信号通路的关系。方法:清洁级健康雄性SD大鼠36只,2月龄,体重200~220 g,采用随机数字表法分为3组(n=12):假手术组(S组)、压力超负荷组(POL组)、依达拉奉组(E组)。采用结扎胸主动脉8周的方法制备心脏压力超负荷模型。结扎血管后,POL组每日腹腔注射0.9%氯化钠10 ml/kg,E组每日腹腔注射依达拉奉10 mg/kg,连续8周。于模型制备成功后,采用二维超声仪测定左室射血分数(EF)、心室缩短分数(FS);放血处死大鼠取心脏,称重后计算心重/体重(HW/BW)比值,取心肌组织,HE染色后测定心肌细胞横截面积(MSA),采用Masson染色法测定胶原容积分数(CVF),采用免疫组化法测定AT1R和StAR表达,采用Western blot法测定细胞外调节蛋白激酶1/2(ERK1/2)和p38 MAPK磷酸化水平(p-ERK1/2/ERK1/2比值、p-p38 MAPK/p38 MAPK比值),采用ELISA法测定醛固酮含量。结果:与S组比较,POL组HW/BW比值、MSA和CVF升高,EF和FS降低,AT1R和StAR表达上调,p-ERK1/2/ERK1/2比值、p-p38 MAPK/p38 MAPK比值和醛固酮含量升高(P<0.05);与POL组比较,E组HW/BW比值、MSA和CVF降低,EF和FS升高,AT1R和StAR表达下调,p-ERK1/2/ERK1/2比值、p-p38 MAPK/p38 MAPK比值和醛固酮含量降低(P<0.05)。结论:依达拉奉抑制大鼠压力超负荷致心肌重构形成的机制可能与抑制AT1R/MAPKs/StAR信号通路激活有关。
Objective To evaluate the relationship between edaravone-induced inhibition of pressure overload-induced myocardial remodeling and angiotensinⅡtype 1 receptor(AT_(1)R)/mitogen activated protein kinases(MAPKs)/steroidogenic acute regulatory protein(StAR)signaling pathway in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 2 months,weighing 200-220 g,were divided into 3 groups(n=12 each)using a random number table method:sham operation group(S group),pressure overload group(POL group)and edaravone group(E group).The cardiac pressure overload was induced by ligation of thoracic aorta for 8 weeks.After the model preparation,0.9%sodium chloride 10 ml/kg was intraperitoneally injected daily in group POL,and edaravone 10 mg/kg was given instead in group E for 8 consecutive weeks.After the model was successfully established,the left ventricular ejection fraction(EF)and ventricular shortening fraction(FS)were measured by two-dimensional ultrasound.The animals were sacrificed by bloodletting,and the heart weight/body weight ratio(HW/BW ratio)was calculated.Myocardial tissues were obtained for determination of the cross-sectional area(MSA)after HE staining,the collagen volume fraction(CVF)(using Masson′s staining),the expression of AT_(1)R and StAR(by immunohistochemistry),extracellular signal-regulated kinase 1/2(ERK1/2)and p38 MAPK phosphorylation levels(p-ERK1/2/ERK1/2 ratio and p-p38 MAPK/p38 MAPK ratio)(by Western blot)and the aldosterone content(by enzyme-linked immunosorbent assay).Results Compared with group S,the HW/BW ratio,MSA and CVF were significantly increased,EF and FS were decreased,AT_(1)R and StAR expression was up-regulated,and p-ERK1/2/ERK1/2 ratio,p-p38 MAPK/p38 MAPK ratio and aldosterone content were increased in group POL(P<0.05).Compared with POL group,the HW/BW ratio,MSA and CVF were significantly decreased,EF and FS were increased,AT_(1)R and StAR expression was down-regulated,and p-ERK1/2/ERK1/2 ratio,p-p38 MAPK/p38 MAPK ratio and aldosterone content were decreased in
作者
张玮玮
余淑珍
郑李娜
王亭
李荣山
Zhang Weiwei;Yu Shuzhen;Zheng Lina;Wang Ting;Li Rongshan(Department of Anesthesiology,Shanxi Provincial People′s Hospital Postdoctoral Workstation of Shanxi Provincial People′s Hospital,Taiyuan 030012,China;Department of Anesthesiology,Shanxi Provincial People′s Hospital,Taiyuan 030012,China;Department of Nephrology,Shanxi Provincial People′s Hospital Postdoctoral Workstation of Shanxi Provincial People′s Hospital,Taiyuan 030012,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2021年第5期625-629,共5页
Chinese Journal of Anesthesiology
基金
山西省回国留学人员科研资助项目(2020-181)
山西省留学人员科技活动项目择优资助(2019-15)。
