汉防己甲素对急性百草枯中毒致肺损伤的实验治疗研究

Experimental study on therapeutic efficacy of tetrandrine on lung injury induced by acute paraquat poisoning

目的探讨汉防己甲素（TET）对急性百草枯中毒所致肺损伤的拮抗作用。方法雄性Wistar大鼠随机分为对照组（7只）、未治疗组（32只）和治疗组（32只）。治疗组与未治疗组大鼠用百草枯（15mg／kg）一次性腹腔注射染毒。治疗组于百草枯染毒后6h经口给予汉防己甲素30mg／kg，1次／d；未治疗组给予等体积的生理盐水；对照组一次性腹腔注射等体积生理盐水。分别测定不同处理后3、7、14和21d时大鼠血浆和肺匀浆中丙二醛（MDA）含量及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—Px）活力，并观察肺组织结构改变。结果染毒3d时，未治疗组血浆及匀浆中MDA含量分别为（3．65±0．44）nmol／ml、（9．54±0．92）nmol／mgpro，均高于对照组，差异有统计学意义（P〈0．01）；未治疗组3d时血浆和3、7d时匀浆中GSH—Px活力与对照组相比明显降低，差异有统计学意义（P〈0．05）；未治疗组3d时血浆和14d时匀浆中的SOD活力与对照组相比明显降低，差异有统计学意义（P〈0．05）；各时点治疗组血浆、匀浆中MDA含量与未治疗组比较，差异无统计学意义（P〉0．05）。3d时治疗组血浆SOD活力与未治疗组相比明显增高，差异有统计学意义（P〈0．01）。治疗组血浆中GSH-Px活力虽均高于未治疗组，但差异均无统计学意义（P〉0．05）。治疗组肺纤维组织积分均低于未治疗组，差异有统计学意义（P〈0．01）。结论TET对急性百草枯中毒大鼠血浆中SOD和GSH—Px活力降低有一定的拮抗作用，可减轻肺纤维化。

Objective To investigate the antagonistic efficacy of tetrandrine （TET） on lung injury induced by acute paraquat poisoning. Methods Male Wistar rats were randomly divided into three groups （control group, non-treatment group and treatment group）. The tetrandrine of 30 mg/kg was given by gastrogavage six hours after 32 rats were intraperitoneally injected with paraquat 15mg/kg （treatment group）. Then the same dose of tetrandrine was given once a day. Normal saline of the same volume was given by gastrogavage in another 32 rats intraperitoneally injected with paraquat 15 mg/kg （non-treatment group）. Seven rats were intraperitoneally injected by normal saline as the control group. Levels of maleic dialdehyde （MDA）, activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in plasma and the lung homogenate of three groups were determined at 3 d,7 d, 14 d and 21 d after exposure to paraquat. Histological. changes of the lungs were observed. Results The levels of MDA at 3 d both in plasma [（3.65±0.44）nmol/ml] and the lung homo- genate [（9.54±0.92）nmol/mg pro] of the non-treatment group significantly increased compared with the control group （P〈0.01） ,the activities of GSH-Px and SOD in plasma at 3 d were significantly less than the control group （P〈0.05 or P〈0.01 ）, the activities of GSH-Px（ 3 d, 7 d ） and SOD （7 d, 14 d ） in the lung homogenate were significantly less than the control group （P〈0.05）. There were no significant difference in the levels of MDA both in plasma and the lung homogenate between the treatment group and the non-treatment group （P〉0.05）. The SOD activities of treatment group on the third day was significantly increased compared with the non-treatment group （P〈0.01 or P〈0.05）. Although the activities of GSH-Px in plasma and the lung homogenate of the treatment group on the third day were increased,there was no significantly difference compared with the non-treatment group （P〉0.05）. The integral score of pulmonary fibrosis in the treatment group were significantly lower than in the non-treatment group（P〈0.01 ）. Conclusion TET has antagonistic effect against acute toxicity of paraquat through significant reduction of pulmonary fibrosis.