大蒜辣素对肺动脉高压模型大鼠的保护作用及机制研究

Study on Protective Effect and Mechanism of Allicin on Rats with Pulmonary Hypertension Model

目的观察大蒜有效成分大蒜辣素对肺动脉高压模型大鼠的保护作用,探讨其可能的作用机制。方法将SD雄性大鼠随机分为正常组、模型组、大蒜辣素组和波生坦组。腹腔注射野百合碱法制备肺动脉高压大鼠模型,造模即日起灌胃给药,每天1次,连续4周。小动物心脏超声系统检测肺动脉和右心室射血功能指标;称量右心室游离壁质量,计算右心肥厚指数;HE和Masson染色法分别观察肺动脉及右心室的组织病理形态和纤维化程度;增殖细胞核抗原检测法评估肺动脉平滑肌细胞增殖情况;小血管张力描记技术评估肺动脉舒缩功能。结果与正常组比较,模型组大鼠肺动脉和右心射血功能明显下降;肺动脉管壁明显增厚,内皮表面粗糙、呈连续性破坏;肺动脉和右心室组织胶原沉积明显增加;肺动脉平滑肌细胞增殖明显增加;肺动脉对5-羟色胺(5-HT)收缩反应强度明显增强、对乙酰胆碱(ACh)的舒张反应明显下降(P<0.05,P<0.01)。与模型组比较,大蒜辣素组和波生坦组肺动脉和右心射血功能、组织病理形态和纤维化程度及肺动脉平滑肌细胞增殖均明显改善(P<0.05,P<0.01);大蒜辣素组肺动脉对5-HT和ACh的收缩和舒张反应均明显改善(P<0.01)。与波生坦组比较,大蒜辣素对右心室射血功能及肺动脉结构的改善作用均明显增强(P<0.01)。结论大蒜辣素对肺动脉高压模型大鼠肺动脉和右心射血功能、组织病理形态、纤维化程度及肺动脉平滑肌细胞增殖、肺动脉收缩和舒张功能均有明显改善作用,其作用在一定程度上优于波生坦;大蒜辣素的上述作用与其抑制平滑肌细胞增殖、改善血管舒缩功能有关。

Objective To investigate the protective effect of allicin(the active ingredient of garlic)on rats with pulmonary hypertension,and to explore the possible mechanisms.Methods The SD male rats were randomly divided into normal,model,allicin and Bosentan groups.The pulmonary hypertension rat model was prepared by intraperitoneal injection of monocrotaline and administered with drug by gavage once a day for 4 weeks after modeling.Small animal cardiac ultrasound system was used for the detection of pulmonary artery and right ventricular ejection function indices.The free wall of the right ventricle was weighed,and the right heart hypertrophy index was calculated.Histopathological morphology and fibrosis in the pulmonary artery and right ventricle were observed by HE and Masson staining,respectively.Detection of proliferating cell nuclear antigen was performed to assess pulmonary artery smooth muscle cell proliferation.Technique for recording small vessel tension was adopted to test pulmonary artery diastolic function.Results In comparison with the normal group,significant reduction in pulmonary artery and right heart ejection function in model rats were found.The pulmonary artery wall was thickened,and the surface of the endothelium showed rough and continuous damage.Collagen deposition in pulmonary artery and right ventricular tissue was significantly increased.The proliferation of pulmonary artery smooth muscle cells was significantly increased.Pulmonary artery contractile response to 5-hydroxytryptamine was significantly enhanced,while the diastolic response to acetylcholine was significantly decreased(P<0.05,P<0.01).In comparison with the model group,pulmonary artery and right heart ejection function,histopathological morphology and degree of fibrosis,as well as pulmonary artery smooth muscle cell proliferation were significantly improved in the allicin and bosentan groups(P<0.05,P<0.01),pulmonary artery systolic and diastolic responses to 5-hydroxytryptamine and acetylcholine were significantly improved in the allicin group(P<0.01).Compared with the bosentan group,allicin had a significantly enhanced effect on the improvement of right ventricular ejection function and pulmonary artery stracture(P<0.01).Conclusion Allicin significantly improved pulmonary artery and right heart ejection function,histopathological morphology,fibrosis,pulmonary artery smooth muscle cell proliferation,pulmonary artery systolic and diastolic function in rats with pulmonary hypertension,and its effect was superior to that of bosentan to some extent.The above effects of allicin are related to its inhibition of smooth muscle cell proliferation and improvement of vasodilatory function.