二氯醋酸钠对大鼠低氧肺动脉高压的预防作用  

The prevention of the dichloroacetate on the development to hypoxia pulmonary artery hypertension in rats

作　　者：徐贤华[1] 彭华生[1] 孙梅芹[1] 肖欣荣[1] 胡猛[1] 王万华[1] 何晓英[1] 陈娟[1] 

机构地区：[1]中国人民解放军成都军区总医院干部病房,四川省成都市610083

出　　处：《实用老年医学》2011年第2期140-143,共4页Practical Geriatrics

基　　金：四川省卫生厅科研课题(090002)

摘　　要：目的研究二氯醋酸钠（DCA）对大鼠在高原环境下形成高原低氧性肺动脉高压的预防作用,以及对高原低氧大鼠肺动脉平滑肌细胞（PASMCs）上电压门控性钾通道亚型Kv2.1基因表达的影响和抑制肺动脉重构的作用方法24只雄性SD大鼠随机平均分为正常对照组（N组）、高原组（HA组）及DCA干预组（DCA＋HA组）。N组置于平原处室内喂养,HA组和DCA＋HA组均同时置于模拟的海拔5000 m高原环境,DCA＋HA组大鼠以DCA按70 mg/（k.gd）灌胃。21 d后测量3组大鼠平均肺动脉压（mPAP）,图像分析技术分析肺动脉（50~150μm）形态改变,用实时荧光定量PCR法检测3组大鼠PASMCs Kv2.1 mRNA,免疫组织化学法观察大鼠PASMCsKv2.1蛋白的表达。结果 HA组大鼠mPAP明显高于N组（P〈0.01）,其肺动脉管壁增厚,管腔狭窄,表现为管壁厚度占外径的百分比（WT%）和管壁面积占总面积的百分比（WA%）明显升高（P〈0.01）,HA组大鼠右心室肥厚指数（右心室/左心室＋室间隔,RV/LV＋S）较N组明显升高（P〈0.01）,而DCA＋HA组mPAP则明显比HA组低（P〈0.01）,并表现血管重构减弱,WT%和WA%明显低于HA组（P〈0.01）,RV/LV＋S下降（P〈0.01）。HA组Kv2.1 mRNA明显低于N组（P〈0.01）,DCA＋HA组Kv2.1 mRNA则明显恢复表达（P〈0.01）。HA组肺动脉壁Kv2.1平均光密度低于N组（P〈0.01）,DCA＋HA组则明显高于HA组（P〈0.01）,蛋白表达呈现相似结果。结论 DCA对于大鼠在高原条件下形成的肺动脉高压具有预防作用,同时能够上调大鼠PASMCs上Kv2.1表达,阻止肺动脉和右心室重构的作用。Objective To investigate the prevention of dichloroacetate（DCA） on development of high altitude pulmonary artery hypertension（HA-PAT）of rats,and to study the effect of DCA on the Kv2.1 expression in pulmonary arterial smooth muscles（PASMCs） and inhibiting the pulmonary artery remodeling of the HA-PAT rats.Methods Twenty-four rats were randomly and averagely devided into normal group（N group）,high altitude group（HA group）,and DCA treated group（DCA＋HA group）.The N group were fed in normal conditions,HA group and DCA＋HA group were fed in a hypobaria and hypoxia chamber simulated to an altitude of 5000 m.In addition,DCA＋HA group rats were treated with DCA [70 mg/（kg·d）]by gastrogavage.Twenty-one days later,the morphologic changes of small pulmonary arterioles were determined by image analysis.Real time PCR,immunohistochemistry were carried out to detect the Kv2.1 expression in PASMCs.Results Compared with the rats in N group,mPAP of HA group were increased and the small pulmonary arteries wall thickened significantly（P0.01）,WT% and WA% were notably increased（P0.01）,however,these changes in DCA＋HA group were not obviously.Furthermore,Kv2.1 of the PASMCs deceased remarkably in HA group compared with N group（P0.01）,but in DCA＋HA group,the Kv2.1 was recovered（P0.01）,the protein expression present similar results.Conclusions The DCA can protect the development of HA-PAT in hypobaria and hypoxia circumstance,and upregulate the expression of Kv2.1 in PASMCs tremendously inhibited in rats fed in high altitude,and inhibit the remodeling of pulmonary arterials and right ventricle.

关 键 词：二氯醋酸钠 高原 肺动脉高压 电压门控性钾通道Kv2.1亚型 预防 

分 类 号：R332[医药卫生—人体生理学]