跨膜蛋白16A与高肺血流性肺动脉高压中炎症反应的关系

Relationship between transmembrane protein 16A and inflammatory response in pulmonary hypertension induced by high pulmonary blood flow

目的探讨跨膜蛋白16A (TMEM16A)与高肺血流性肺动脉高压中炎症反应的关系,为诊治肺动脉高压提供参考依据.方法将30只大鼠随机分为对照组(不做任何处理)、假手术组(除腹主动脉夹闭3 min和不穿刺吻合缝合血管外,其余采用分流组方法处理)和分流组(建立高肺血流性肺动脉高压大鼠模型),给予同样的饲养环境,10周后对3组大鼠的右心室心肌肥厚指数(RVHI)、右心室收缩压(RVSP)、肺血管组织的TMEM16A、肿瘤坏死因子-α(TNF-α)、Raf、p38MAPK蛋白进行检测.结果分流组RVSP、RVHI均显著高于假手术组、对照组,差异均有统计学意义(P<0.05);分流组的TMEM16AmRNA表达及TMEM16A蛋白表达显著高于假手术组与对照组(P<0.05);分流组的TNF-α、Raf、p38 MAPK表达显著高于对照组和假手术组.结论在高肺血流性肺动脉高压大鼠中,TMEM16A介导的钙激活性氯离子通道(CaCC)显著高表达,可能通过MAPK途径影响肺血管炎症.

Objective To explore the relationship between transmembrane protein 16 A(TMEM16 A)and inflammatory response in pulmonary hypertension induced by high pulmonary blood flow,provide a reference basis for diagnosis and treatment of pulmonary hypertension.Methods Thirty rats were randomly divided into control group(without treatment),sham operation group(excluding occlusion of aorta abdominalis for three minutes and not puncturing,anastomosing,and suturing vessels,the other methods were the same as shunt group),and shunt group(establishing rat model of pulmonary hypertension induced by high pulmonary blood flow),the rats in the three groups were fed in the same environment,after 10 weeks,the levels of right ventricular cardiac hypertrophy index(RVHI),right ventricular systolic pressure(RVSP),TMEM16 A in pulmonary vascular tissue,tumor necrosis factor-α(TNF-α),Raf,p38 MAPK protein in the three groups were detected.Results The levels of RVSP and RVHI in shunt group were statistically significantly higher than those in sham operation group and control group(P<0.05).The expression levels of TMEM16 A mRNA and protein in shunt group were statistically significantly higher than those in sham operation group and control group(P<0.05).The levels of TNF-α,Raf,p38 MAPK in shunt group were statistically significantly higher than those in sham operation group and control group.Conclusion TMEM16 A-mediated calcium-activated chloride channel(Ca CC)is high in the rats with pulmonary hypertension induced by high pulmonary blood flow,which may induce pulmonary vascular inflammation via MAPK pathway.