CAJ | 학술논문

目的观察钙敏感受体(CaSR)对高肺血流性肺动脉高压大鼠肺动脉线粒体功能的影响,并探讨其在高肺血流性肺动脉高压形成的作用机制.方法行左肺切除手术建立大鼠肺动脉高压模型.将27只大鼠随机分为3组(n=9),对照组、手术组、手术+钙敏感受体阻滞剂Calhex231组.饲养35 d后,检测各组大鼠肺动脉CaSR mRNA的表达；透视电镜观察肺动脉线粒体超微结构；原位末端转移酶标记(TUNEL)法统计各组大鼠内皮细胞凋亡率.结果大鼠肺动脉内皮细胞CaSR mRNA的相对表达量以2-△△Ct表示,对照组为0.0003±0.0001,手术组为0.0071±0.0041,手术+Calhex231组为0.0011±0.0003,差异有统计学意义(P＜0.05).与对照组比较,手术组肺动脉线粒体膜肿胀,线粒体活力下降,肺动脉内皮细胞凋亡率均明显升高(P＜0.05)；与手术组比较,手术+ Calhex231组线粒体膜肿胀度减轻,活力有所恢复,肺动脉内皮细胞凋亡率明显降低(P＜0.05).结论高肺血流量可引起大鼠肺动脉内皮细胞CaSR的活化,进而调控线粒体途径,诱发肺动脉内皮细胞凋亡,引起肺动脉高压.
목적 관찰개민감수체(CaSR)대고폐혈류성폐동맥고압대서폐동맥선립체공능적영향,병탐토기재고폐혈류성폐동맥고압형성적작용궤제.방법 행좌폐절제수술건립대서폐동맥고압모형.장27지대서수궤분위3조(n=9),대조조、수술조、수술+개민감수체조체제Calhex231조.사양35 d후,검측각조대서폐동맥CaSR mRNA적표체；투시전경관찰폐동맥선립체초미결구；원위말단전이매표기(TUNEL)법통계각조대서내피세포조망솔.결과 대서폐동맥내피세포CaSR mRNA적상대표체량이2-△△Ct표시,대조조위0.0003±0.0001,수술조위0.0071±0.0041,수술+Calhex231조위0.0011±0.0003,차이유통계학의의(P＜0.05).여대조조비교,수술조폐동맥선립체막종창,선립체활력하강,폐동맥내피세포조망솔균명현승고(P＜0.05)；여수술조비교,수술+ Calhex231조선립체막종창도감경,활력유소회복,폐동맥내피세포조망솔명현강저(P＜0.05).결론 고폐혈류량가인기대서폐동맥내피세포CaSR적활화,진이조공선립체도경,유발폐동맥내피세포조망,인기폐동맥고압.
Objective To observe the calcium-sensing receptor (CaSR) high pulmonary blood flow in rats with pulmonary hypertension pulmonary mitochondrial function,and to explore the mechanism of the formation of its high pulmonary blood flow in pulmonary hypertension.Methods Row left lung resection establish a rat model of pulmonary hypertension.27 rats were randomly divided into 3 groups (n =9),the control group,the surgery group,surgery calcium-sensing receptor blockers Calhex231 group.Rats mean pulmonary artery pressure were measured after feeding 35d detect right ventricular/body weight (right ventricle/body weight,RV/BW) and right ventricular/left ventricular interventricular septum (right ventricle/left and lodging to plus septum,RV/LV S) ratio.The test groups the rat pulmonary CaSR mRNA expression; mitochondrial ultrastructure; perspective electronmicroscope pulmonary the TdT-mediated dUTP nick end labeling (TUNEL) method statistics rats in each group rate of endothelial cell apoptosis.Results Rat pulmonary artery endothelial cells CaSR mRNA relative expression levels of 2-△△ct,the control group compared with the control group 0.0003 ±0.0001,0.0071 ±0.0041,the surgery group difference was statistically significant (P ＜ 0.05) ; surgery group pulmonary mitochondrial membrane swelling,mitochondrial activity decreased pulmonary endothelial cell apoptosis was significantly increased (P ＜ 0.05).The surgery Calhex231 rats pulmonary CaSRmRNA relative expression level of 0.0011 ±0.0003,compared with the surgery group decreased significantly (P ＜ 0.05),and reduce the swelling of the mitochondrial membrane,vitality has been restored,the pulmonary endothelial cell apoptosis rate was significantly lower (P ＜ 0.05).Conclusion The high pulmonary blood flow can cause the activation of rat pulmonary artery endothelial cells CaSR regulating mitochondrial pathway to induce apoptosis of pulmonary artery endothelial cells,causing pulmonary hypertension.