黄芪甲苷对大鼠肺缺血再灌注损伤的保护作用及其机制研究

Study on the Protective Effects of Astragaloside Ⅳ to the Rats Suffering from Lung Ischemical Reperfusion Injury and Its Mechanism

目的:研究黄芪甲苷对大鼠肺缺血再灌注损伤的保护作用及其机制。方法:将50只实验用大鼠随机分为假手术组、模型组和黄芪甲苷(20、40、80 mg/kg)组,每组10只;采用夹闭左肺门45分钟后松夹的方法制备肺缺血再灌注损伤大鼠模型,各组分别于术前30分钟腹腔注射给药。再灌注2小时后,测定肺组织湿/干重比(W/D),测定肺组织中抗氧化酶(SOD、GSH-Px、CAT)活性和血清中髓过氧化物酶(MPO)活性、丙二醛(MDA)含量,HE染色法观察肺组织形态结构变化;TUNEL法观察肺组织细胞凋亡状况并计算凋亡指数(Apoptosis Index,AI)。结果:与模型组比较,黄芪甲苷(40、80 mg/kg)组肺组织W/D显著降低,肺组织中SOD、GSH-Px、CAT活性显著升高,血清中MPO活性和MDA含量显著降低,肺组织形态结构变化和肺细胞病变显著减轻,肺细胞凋亡状况明显改善,黄芪甲苷(40、80 mg/kg)组AI显著降低,上述差异均具有统计学意义(P<0.05)。结论:黄芪甲苷对肺缺血再灌注损伤大鼠具有保护作用,作用机制可能与黄芪甲苷能够有效改善抗氧化酶活性、降低氧化应激损伤、减轻肺水肿、抑制细胞凋亡有关。

Objective: To study the protective effects and the mechanism of astragaloside Ⅳto the rats with lung ischemical reperfusion injury. Methods: Fifty rats were randomized into sham operation group, the model group and astragaloside Ⅳ groups(20, 40 and 80 mg/kg), ten rats each group, the rat model was prepared by Hilum occlusion of left lung for 45 minutes and loosening, different groups were medicated by intraperitoneal injection 30 minutes ago before the surgery. After reperfusion for two hours, lung wet/dry weight ratio(W/D) was detected, the contents of MDA, the activity of MPO in the serum, the activity of SOD, GSH-Px and CAT in lung tissue were detected, morphological changes of lung tissue were observed by HE staining method, cellular apoptosis conditions of lung tissue was observed by TUNEL method and apoptosis index(AI) was calculated. Results: Compared with the model group, lung W/D notably decreased in astragaloside IV groups(40 and 80 mg/kg), the activity of SOD,GSH-Px and CAT in lung tissue raised significantly, the activity of MPO and the contents of MDA in the serum lowered significantly, morphological changes of lung and lung cytopathy alleviated significantly, lung cellular apoptosis conditions improved notably, AI decreased notably in astragaloside Ⅳ groups(40 and 80 mg/kg), and the difference all above had statistical meaning(P<0.05). Conclusion: Astragaloside IV shows protective effects to the rats with lung ischemical reperfusion injury, and its mechanism might be related to that astragaloside IV could effectively improve the activity of antioxidase, decrease oxidative stress injury, relieve pulmonary edema and inhibit cellular apoptosis.