大蒜素抑制肺动脉结构变型和肺动脉发生发展作用的观察

目的　用野百合碱（MCT）诱发大鼠肺动脉高压作为动物模型，观察大蒜素治疗后肺动脉结构的变化及血流动力学的改变，并探讨其作用机制。方法　健康雄性Wistar大鼠，以80mg/kg剂量背部皮下一次注射MCT水溶液作为高压组；在此基础上按15mg/(kg*d)日注射大蒜素水溶液作为治疗组；按同等剂量背部皮下注射蒸馏水作为对照组。参考孙波等的右心导管术，测定或观察肺动脉压（PAP），心输出量（CO），全肺阻力（TPR），以及一般血流动力学指标，包括心率（HR）、平均动脉压等。在此基础上，测定血管收缩剂去甲肾上腺素（NE）与血管舒张剂乙酰胆碱（Ach）所引起的肺动脉平均压的变化。随后测量动脉血氧分压、二氧化碳分压、pH值以及动、静脉血红细胞记数。采用微量生物学测定方法，观察离体血管环对乙酰胆碱的舒张反应。光镜测量泡内动脉中膜厚度并计算肌型动脉和非肌型动脉各占泡内动脉数的百分比；电镜观察内皮细胞、平滑肌细胞、胶原的变化以及血小板的变化情况。结果　野百合碱注射28d，高压模型组与正常对照组肺动脉压分别为(5.83±0.22)kPa和(2.91±0.04)kPa(P<0.01)，有显著性差异，结果提示野百合碱诱发大鼠肺动脉高压模型成功。28d时，治疗组与高压组的肺动脉压、全肺阻力、对去甲肾上腺素和乙酰胆碱的反应性均有显著性差异（P<0.01）；与高压组相比，大蒜素治疗组的血气状况有明显改善。从形态结构来看，与高压组相比，治疗组大鼠肺动脉中膜增厚程度减轻，肌型化动脉减少，Ⅰ型胶原堆积减少，内皮细胞病变程度减轻，未见血小板聚集和粘附。结论　①大蒜素具有抑制血小板聚集和脱颗粒作用。②大蒜素具有抑制肺动脉结构变型，抑制PAP、TPR、血管反应性增高和改善血气的作用。③大蒜素治疗过程中，未发现任何副作用，因此，大蒜素可能成为一种较理想的治疗PAH药物。

Studies on the role ofallicin in inhibiting pulmonary remodeling and in the development of pulmonary artery

Objective　To examine whether the allicin has beneficial effects in the treatment of pulmonary hypertension and ultr astructural changes induced by monocrotaline (MCT). Methods One hundred and ninety eight male Wi star rats weighing from 180 g to 200 g were randomly divided into three groups: ① Pulmonary hypertension (PH) group (n=66) treated with MCT(80 mg/kg, ih); ② Allicin group (n＝66)treated with MCT+Allicin 〔15 mg/(kg*d)〕;③ Con trol group (n=66 ), treated with NS. Results　The results showed that:① In MCT group, the pulmonary arterial pressure increased to maximum level at d 28 a fter injection of MCT attaining to (5.83±0.22) kPa as compared to the control of (2.91±0.04) kPa (P<0.01)； ② In allicin group, the pulmonary arterial p ressure decreased to (4.51±0.22) kPa and the total pulmonary resistance (TPR) d e creased from (1 483.05±157.97)U (MCT group) to (637.15±19.26)U (P<0.01) ；③ The responsiveness of pulmonary artery to norepinephrine(10-4 mol/L ) was significantly reduced in allicin group； ④ The blood gas (PO2, PCO2 and pH) changes induced by MCT was also remarkably attenuated by administration of allicin (P<0.01)； ⑤ All of the ultrastructural changes (including the thickening of pulmonary media layer, musculinization of pulmonary artery, decrea se in Ⅰ-type collagenous fibers, pathologic changes of endothelial cells and p l atelet aggregation, etc.) were significantly alleviated by administration of all icin. The mechanisms responsible for the actions of allicin were discussed. Co nclusion　It is indicated that allicin has definite beneficial ef fects in the treatment of pulmonary hypertension.