【作者】 邢西迁；

【导师】 吴尚洁；

【作者基本信息】 中南大学 ， 呼吸内科， 2007， 硕士

【摘要】 目的：观察阿托伐他汀对野百合碱(MCT)诱导的肺动脉高压大鼠的影响，探讨核因子-κappaB(NF-κB)在MCT诱导的肺动脉高压发病中的作用和阿托伐他汀对MCT诱导的肺动脉高压大鼠肺组织NF-κB表达的影响。方法：将24只健康雄性SD大鼠随机分为正常对照组(对照组)，MCT诱导的肺动脉高压组(MCT组)，阿托伐他汀干预组(AS组)，每组8只。MCT组和AS组分别一次性腹部皮下注射MCT(60mg／kg)，对照组以等量生理盐水代替。AS组自注射MCT之日起以阿托伐他汀(10mg／kg)灌胃，每日一次。MCT组以生理盐水(10ml／kg)每日灌胃。3周后达实验终点，测定大鼠平均肺动脉压(mPAP)、平均颈动脉压(mCAP)，计算右心室肥大指数(RVHI)。肺组织切片进行苏木素-伊红(HE)染色，光镜下观察肺组织形态学的改变，并计算肺中小动脉管壁厚度占血管外径的百分比(WT％)和肺动脉管壁面积／管总面积的百分比(WA％)，以此反映肺血管重建情况。采用免疫组化法观察大鼠肺组织NF-κB表达的变化。结果：1．MCT组大鼠的mPAP和RVHI均显著高于对照组(P＜0.01)，而AS组大鼠的mPAP和RVHI均较MCT组明显降低(P＜0.01)，但AS组大鼠的mPAP和RVHI均较对照组明显增高(P＜0.05)。三组大鼠的mCAP没有明显差别(P均＞0.05)。2．对照组大鼠肺中小动脉管壁薄，管腔大；MCT组大鼠肺中小动脉，管壁厚度明显增加，管腔面积明显变小，伴有明显的血管周围炎；AS组大鼠肺中小动脉管壁厚度较MCT组明显减小，管腔面积较MCT组明显增大，血管周围炎明显减轻。3．MCT组大鼠肺中小动脉WT％和WA％均明显高于对照组(P)＜0.01)，AS组大鼠肺中小动脉WT％和WA％均明显低于MCT组(P＜0.01)，但AS组大鼠肺中小动脉WT％和WA％均明显高于对照组(P＜0.01)。4．大鼠细支气管上皮细胞NF-κB核阳性细胞百分比：MCT组明显高于对照组(P＜0.01)，AS组明显低于MCT组(P＜0.01)，但明显高于对照组(P＜0.01)。5．大鼠细支气管上皮细胞NF-κB核阳性细胞百分比与mPAP、肺中小动脉WT％和WA％成明显正相关(P均＜0.01)。结论：阿托伐他汀可降低MCT所致的肺组织NF-κB的表达，具有抑制MCT诱导的肺部炎症、肺血管重建和肺动脉高压形成的作用。更多还原

【Abstract】 Objective: To investigate the effects of atorvastatin onmonocrotaline (MCT)-induced pulmonary hypertension in rats and theexpression of nuclear factor-kappa B (NF-κB) in lung.Methods: Twenty-four male SD rats were randomly divided intothree groups with eight rats each group: control group, MCT group andatorvastatin group (AS group). The rats in MCT and AS group were givena single subcutaneously injection of MCT (60mg/kg) and the rats incontrol group were injected with saline. Atorvastatin (10mg/kg/d) weregiven orally for 21 days to the rats in AS groups and vehicle were givento the rats in MCT group since the day when rats were injected MCT. At22 days, mean pulmonary arterial pressure (mPAP), mean carotidpressure (mCAP) and right ventricular hypertrophy index (RVHI) weremeasured. The index of wall thickness of pulmonary arteriole wasmeasured by a computerized image analyzer. The expression of NF-κB inbronchioles was observed by immunohistochemistry.Results:1. The mPAP and RVHI were increased significantly in MCT groupthan that in control group (P＜0.01). This increase in mPAP and RVHI was partially prevented by atorvastatin(P＜0.01). There was no significantdiscrepancy on mCAP between three groups (P＞0.05).2. The thickness of the medial wall of pulmonary medial arteries andarteriole was significantly increased in MCT group as compared withcontrol group. Large numbers inflammatory cells congregated around thesmall vascular and in the pulmonary interstitial in MCT group.Atorvastatin treatment was associated with a significant reduction ofMCT-induced thickening and the number of inflammatory cells.3. WT％and WA％of pulmonary medial arteries and arteriole wereincreased significantly in MCT group than that in control group (P＜0.01).This increase in WT％and WA％was partially prevented by atorvastatin(P＜0.01).4. The percentage of positive cells for NF-κB nuclear staining inbronchiolar epithelial cells was significantly increased in MCT groupthan that in the control group (P＜0.01), but in AS group, it wassignificantly decreased than that in the MCT group(P＜0.01).5. The percentage of positive cells for NF-κB nuclear staining inbronchiolar epithelial cells was positively correlated with mPAP andWT％and WA％of pulmonary medial arteries and arteriole(P＜0.01,respectively).Conclusions: Atorvastatin could reduce NF-κB expression ofbronchiolar induced by MCT, prevent MCT-induced inflammatory response, pulmonary vascular remodeling and the development ofpulmonary hypertension.更多还原