沙格雷酯对野百合碱诱导的肺动脉高压大鼠肺动脉TGF-β1/Smads信号通路的影响  

Effects of sarpogrelate on the TGF-β1 / Smads signal pathway in monocrotaline-induced pulmonary arterial hypertension rats

作　　者：韩新源[1] 陈春燕[2] 解翠[1] 王飞宇[1] 李秀红[1] 田红燕[2] 

机构地区：[1]陕西省人民医院心内科,西安710068 [2]西安交通大学第一附属医院周围血管科

出　　处：《山西医科大学学报》2016年第8期706-710,共5页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(81170294)

摘　　要：目的观察盐酸沙格雷酯(5-HT_(2A)受体拮抗剂)对野百合碱肺动脉高压模型大鼠肺动脉结构和肺动脉TGF-β1/Smads信号分子表达的影响。方法 SD大鼠随机分为对照组、肺动脉高压模型组(模型组)及沙格雷酯干预组(沙格雷酯组)。其中模型组和沙格雷酯组采用野百合碱单次腹腔注射法建立肺动脉高压大鼠模型;同时,沙格雷酯组再给予盐酸沙格雷酯灌胃。干预21 d时分别测定平均肺动脉压力(m PAP),计算右心肥厚指数,HE染色观察肺动脉结构的变化;采用Mallory三色染色评估肺动脉纤维化程度;Western blot检测肺动脉转化生长因子β1(TGF-β1)及其下游分子磷酸化的Smad3蛋白的表达水平,以评估TGF-β1/Smad3信号通路的活化。结果与对照组相比,干预21 d时模型组大鼠的m PAP、右室肥厚指数明显升高(P<0.05);肺组织HE染色结果显示,模型组肺动脉管壁明显增厚,管腔狭窄,纤维组织增生;肺动脉中TGF-β1、p-Smad3蛋白表达明显升高(P<0.01)。与模型组相比,沙格雷酯组m PAP、右室肥厚指数明显降低(P<0.05);管腔狭窄程度也明显改善,肺动脉管壁纤维化程度减低(P<0.01);肺动脉中TGF-β1、p-Smad3蛋白表达明显降低(P<0.01)。结论沙格雷酯抑制野百合碱动物模型的肺动脉纤维化及改善肺动脉高压程度,这一作用可能是通过抑制TGF-β1/Smad3信号通路的活化而实现的。Objective To explore the effects of sarpogrelate（5-HT2A receptor antagonist） on the structure of pulmonary artery and the TGF-β1/Smads signal pathway in monocrotaline-induced pulmonary arterial hypertension（PAH） rats. Methods The rats were divided into control group, model group and sarpogrelate group. The rats were intraperitoneally injected with monocrotaline（MCT） once to induce the pulmonary artery hypertension in model group on and sarpogrelate group, and then the rats were additionally given sarpogrelate by gavage in sarpogrelate group. On the 21st day after treatment, the mean pulmonary arterial pressure （mPAP） was measured and the right ventricular hypertrophy index was calculated. HE staining method was used to observe the morphologic changes of peripheral pulmonary artery. Mallory trichrome staining was used to evaluate the extent of pulmonary arterial wall fibrosis. Western blot was used to detect the TGF-β1 and p-Smad3 protein expression in pulmonary arteries. Results Compared with control group, the mPAP and right ventricular hypertrophy index were increased in model group on the 21st day after treatment （P 〈 0.05 ）, the pulmonary arterial wall became thick and the deposition of collagen drastically increased, and the protein levels of TGF-β1 and p-Smad3 were elevated （P 〈 0. 01 ）. Compared with model group, the mPAP and RV hypertrophy decreased in sarpogrelate group （P 〈 0.05 ）, the PA wall became thin and the fibrosis of pulmonary arterial wall was decreased （P 〈 0. 01 ）. The protein levels of TGF-β1and p-Smad3 in PA were significantly lower in sarpogrelate group than in model group （ P 〈 0.01 ）. Conclusion Sarpogrelate can improve the fibrosis and pulmonary arterial hypertension in PAH rats and TGF-β1/Smads signal pathway may be involved in this process.

关 键 词：沙格雷酯 肺动脉高压 5-羟色胺 转化生长因子 肺血管重构 

分 类 号：R543.2[医药卫生—心血管疾病]