西地那非抑制高肺血流肺动脉高压大鼠肺血管重构和上调肺血管Kv1．5mRNA表达  

Sildenafil inhibits pulmonary vascular remodeling and up-regulates voltage-gated potassium channel Kv1. 5 mRNA expression in secondary pulmonary hypertension due to left-to-right shunt in rats

作　　者：胡蕾[1] 谈林华[1] 林隆[1] 何小军[1] 范佳杰[1] 

机构地区：[1]浙江大学医学院附属儿童医院外科监护室,杭州310003

出　　处：《中华小儿外科杂志》2010年第7期536-540,共5页Chinese Journal of Pediatric Surgery

摘　　要：目的观察高肺血流肺动脉高压大鼠肺血管结构重建和肺血管电压依从钾通道Kv1．5mRNA表达变化，探讨口服西地那非对高肺血流肺动脉高压大鼠肺血管重构及肺血管电压依从钾通道Kv1．5mRNA表达的影响。方法将27只雄性SD大鼠随机分为对照组（n=9）、分流组（n=9）、分流＋西地那非组（n=9）。后两组大鼠通过腹主动脉-下腔静脉分流术建立高肺血流肺动脉高压动物模型。对分流＋西地那非组大鼠每天灌胃枸橼酸西地那非10mg·kg^-1·d^-1，对照组和分流组每天灌胃等量生理盐水。11周后，测定肺动脉平均压（n1PAP）及肺动脉收缩压（sPAP）；观察右室肥厚程度，计算右室重量／（左室＋室间隔）重量比值，以[RV／（LV＋S）]表示；计算肺中、小血管肌型动脉相对中膜厚度（RMT）；采用实时荧光RT-PCR定量法观察大鼠肺血管电压依从钾通道Kv1．5mRNA表达。结果与对照组比较，分流组大鼠TnPAP、sPAP、RV／（LV＋S）比值显著增高（P〈0．01），RMT显著增加（P〈0．01），肺血管Kv1．5mRNA表达水平显著降低（P〈0．01）。与分流组相比，分流＋西地那非组H1PAP、sPAP、RV／（LV＋s）比值显著低于分流组（P〈0．01），RMT显著降低（P〈0．01），肺血管Kv1．5mRNA表达水平显著升高（P〈0．01）。分流＋西地那非组mPAP、sPAP、Rv／（LV＋S）比值和RMT与对照组比较，差异均无显著性意义（P〉0．05）；两组大鼠Kv1．5mRNA表达水平也无显著性差异（P〉0．05）。结论高肺血流肺高压大鼠肺血管发生重构并且其肺血管Kv1．5mRNA表达下降，而口服枸橼酸西地那非抑制高肺血流肺高压大鼠肺血管重构和上调肺血管Kv1．5mRNA表达。Objective To investigate the effects of sildenafil on pulmonary vascular remodeling and voltage-gated potassium channel Kv1. 5 mRNA expression of pulmonary vasculature in secondary pulmonary hypertension due to left-to-right shunt in rats. Methods Male twenty-seven SD rats were randomly divided into sham group （n = 9）, shunt group （n = 9） and shunt ＋ sildenafil group （n = 9）. A left-to-right shunt was established on shunt group and shunt ＋ sildenafil group rats by making fistula between abdominal aorta and inferior vena cava. Rats of the shunt ＋ sildenafil group were admin- istered sildenafil by gastric garage at a dose of 10 mg·kg^-1.d^-1 ; whereas the rats of the sham group and the shunt group were fed with the same amount of saline. Eleven weeks later, mean pulmonary artery pressure （mPAP） and systolic pulmonary artery pressure （sPAP） were measured. The ratio of right ventricular mass to left ventricular plus septal mass [RV/（LV ＋ S）] was also calculated and taken as a marker of the severity of right ventricular hypertrophy. The pathological changes of pulmonary vasculature were evaluated by calculating the relative medial thickness （RMT） of middle and small pulmonary muscularized arteries. The voltage-gated potassium channel Kv1. 5 mRNA expression of pulmonary vasculature was quantified using real-time PCR. Results Compared with the rats of sham group, the rats of shunt group had higher mPAP, sPAP, RV/（LV ＋ S） ratio, and RMT of middie and small pulmonary muscularized （P〈0.01）, while the Kv1. 5 mRNA expression significantly decreased in pulmonary vasculature （P〈0. 01）. Compared with the rats of shunt group, the rats of shunt ＋ sildenafil group had lower mPAP, sPAP, RV/（LV＋ S） ratio, and RMT （all P〈0. 01）, the levels of Kv1. 5 mRNA expression were significantly up-regulated （P〈0. 01）. Between the sham group and the shunt ＋ sildenafil group, no difference of mPAP, sPAP, RV/ （LV＋ S） ratio, Kv1. 5 mRNA expression, and RMT was found

关 键 词：西地那非 Kv1.5钾通道 高血压 肺性 

分 类 号：R965[医药卫生—药理学]