阿司匹林干预野百合碱诱导的大鼠肺动脉高压的研究

目的探讨阿司匹林对野百合碱(MCT)诱导的大鼠肺动脉高压的作用。方法雄性Sprague Dawley(SD)大鼠120只,随机分为6组,每组20只,分别为:正常对照组(Ctrl组)、肺动脉高压组(PAH组)和阿司匹林不同剂量治疗组(ASA 0.5组,ASA 1组,ASA 2组,ASA 4组)。PAH组、阿司匹林各剂量治疗组于第0天一次性腹腔注射MCT 50 mg/kg。从第l天开始,阿司匹林各剂量治疗组分别给予阿司匹林0.5、1.0、2.0 mg·kg~(-1)和4.0mg·kg~(-1)·d~(-1)灌胃,共30d。第31天,对各组大鼠进行以下检测:(1)统计大鼠的体质量和生存率;(2)右心导管法测定肺动脉收缩压(sPAP);(3)心脏大体标本测定右心室肥厚指数(RVHI);(4)肺组织染色切片,运用IPP 6.0图像分析软件测定肺小动脉增厚指数(PATI)。结果与PAH组比较,ASA 2组和ASA 4组体质最增加(464.6±62.6)g和(473.2±77.2)g比(424.9±68.5)g,均为P<0.05];ASA各治疗组合计生存率较PAH组明显提高(83.75%比60.00%,P<0.05);与PAH组比较,ASA各治疗组sPAP明显下降(均为P<0.05),RVHI显著降低(均为P<0.05);除ASA 0.5组以外,其他阿同匹林治疗组的PATI较.PAH组明显降低(均为P<0.05)。结论阿司匹林1、2 mg·kg~(-1)·d~(-1)和4 mg·kg~(-1)·d~(-1)能有效降低野百合碱诱导的肺动脉高压大鼠的肺动脉压力,减轻右心室肥厚和肺小动脉增生。

The effects of aspirin on monocrotaline-induced pulmonary arterial hypertension in rats

Objective To explore the effects of aspirin on moncrotaline-induced pulmonary arterial hypertension in rats. Methods 120 Sprague-Dawley rats were randomly divided into six groups with each for 20： normal control group （Ctrl group） , untreated pulmonary arterial hypertension group （PAH group） and various aspirin-dosage treated pulmonary arterial hypertension group （ ASA 0. 5, 1.0, 2. 0 and 4. 0 mg ~ kg - 1 . d - 1 by intragastrically after monoerotaline injection from day 1 to day 30 ）. The pulmonary arterial hypertension was induced by intraperitoneal injection of 50 mg/kg monocrotaline on day 0. On day 31, results were measured as following： （1）Survival rates and weights were measured; （2） Right heart catheter was performed to measure systolic Pulmonary Arterial Pressure （sPAP） ; （3）Heart specimens were separated and weighed to determine the Right Ventricular Hypertrophy Index （RVHI） ; （4）With pulmonary arterioles staining, Pulmonary Arterioles Thickness Index （PATI） were evaluated by IPP 6. 0 image analysis software. Results In comparison with PAH group, weights in ASA 2 group and ASA 4 group were increased （ P 〈 0. 05 respectively）. Survival rates were significantly increased in overall ASA treatment group compared with PAH group （ P 〈 0.05 respectively ）. sPAPs and RVHIs in various ASA treatment group were significantly decreased than that in PAH group （ P 〈 0. 05 respectively） ; PATIs in ASA treatment group, except ASA 0. 5 group, were significantly decreased than that in PAH group （P 〈 0. 05 respectively）. Conclusions Aspirin （ ASA 1, ASA 2 and ASA 4） could reduce pulmonary arterial pressure,attenuates right ventricular hypertrophy and pulmonary arterioles proliferation in monocrotaline-induced pulmonary arterial hypertension model.