西地那非对野百合碱诱导的大鼠肺动脉高压中Notch-1/Jagged-1通路的影响研究  

Effects of sildenafil on Notch-1/Jagged-1 pathway in rats with monocrotaline-induced pulmonary arterial hypertension

作　　者：向贻佳[1] 蔡昌宏 吴勇辉 叶士勇[1] 赵欢 曾春来[1] XIANG Yijia;CAI Changhong;WU Yonghui;YE Shiyong;ZHAO Huan;ZENG Chunlai(Department of Cardiology,The Fifth Affiliated Hospital of Wenzhou Medical University,Lishui 323000,China)

机构地区：[1]丽水市中心医院心血管内科,323000 [2]丽水市中心医院病理科,323000

出　　处：《心电与循环》2021年第6期581-584,589,F0003,共6页Journal of Electrocardiology and Circulation

摘　　要：目的探讨西地那非对野百合碱诱导的大鼠肺动脉高压中Notch-1/Jagged-1信号通路的作用。方法42只大鼠分为模型组16只,西地那非组16只及对照组10只。模型组及西地那非组一次性皮下注射野百合碱溶液(60 mg/kg)建立肺动脉高压模型,造模3周后西地那非组灌胃西地那非100 mg·kg^(-1)·d^(-1),连续2周,其余两组灌胃等体积0.9%氯化钠注射液。第5周末采用右心导管法测右心室收缩压(RVSP),取心脏分别称重右心室、左心室及室间隔,计算右心室肥厚指数(RI)。采用HE及Masson染色观察肺小动脉结构及纤维化情况。采用Western blot法及免疫组化法检测Notch-1、Hes-1、Jagged-1及α-SMA表达。结果模型组RVSP和RI均高于对照组和西地那非组,差异均有统计学意义(均P<0.05)。HE及Masson染色显示,与对照组比较,模型组肺小动脉明显增厚、纤维化增加,西地那非组肺小动脉结构异常较模型组改善。模型组Notch-1、Hes-1、Jagged-1及α-SMA表达水平均高于对照组,西地那非组Notch-1、Hes-1、Jagged-1及α-SMA表达水平均低于模型组,差异均有统计学意义(均P<0.05)。结论西地那非能够抑制野百合碱诱导的大鼠肺动脉高压中Notch-1/Jagged-1信号通路。Objective To investigate the effect of sildenafil on Notch-1/Jagged-1 pathway in rats with monocrotaline-induced pulmonary artery hypertension(PAH).Methods Forty-two Rats were divided into control(n=10),monocrotaline(MCT,n=16),and MCT+SILD(n=16)groups.PAH model was established by subcutaneously injection of MCT(60 mg/kg)in MCT and MCT+SILD groups.Three weeks later after establishment of the model,Sildenafil(100 mg·kg^(-1)·d^(-1))was administrated orally for 2 weeks in MCT+SILD group,while 0.9%saline was used in the same dosage in other two groups.At the end of the fifth week,the right ventricular systolic pressure(RVSP)was measured via right heart catheterization.The right ventricle,left ventricle and interventricular septal weight was determined.The right ventricular hypertrophy index(RI)was calculated.HE and Masson staining were used to observe pulmonary vascular structure and fibrosis.Western blots and immunohistochemical methods were used to measure the expression of Notch-1、Hes-1、Jagged-1 andα-SMA.Results RVSP and RI were significantly higher in MCT group than in the control group and MCT+SILD group(all P<0.05).Pulmonary arteriolar wall thickness and fibrosis were increased in MCT group than in the control group.Pulmonary vascular abnormality was improved in MCT+SILD group compared with MCT group.The expression of Notch-1,Hes-1,Jagged-1 andα-SMA was significantly higher in MCT group than in the control group and significantly lower in MCT+SILD group than in MCT group(all P<0.05).Conclusion Sildenafil may suppress Notch-1/Jagged-1pathway in rats with monocrotaline-induced PAH.

关 键 词：肺动脉高压 西地那非 NOTCH-1 Hes-1 JAGGED-1 

分 类 号：R544.1[医药卫生—心血管疾病]