抗核药物致肝脏损害电镜观察

摘要

Objective:To study the ultrastructure of hepatic lesion induced by antitubercular drugs. Methods:152 healthy adult rats, weighing about 250~300g,half male and half female, were randomly divided into 8 groups and given different drugs. Control group:NS;group H:isoniazid(INH H);group R:rifampicin (RFP R);group Z:pyrazinamide (PZA Z);group HR:INH+RFP;group HZ:INH+PZA;group RZ:RFP+PZA;group HRZ: INH+RFP+PZA. Rats were given 5.5 times adult clinic therapeutic dose by intragastria administration,once per day,for 10 days.The degrees of hepatic lesion were measured by means of pathology, and the effects of INH, RFP and PZA on hepatic tissues were observed. Results:Some mitochondrions in the liver cells dissolve,rough surfaced endoplasmic reticulum degranulation,smooth surfaced endoplasmic reticulum pool dilatation,the fat particles in the cell increase,hepatin particle apparently increase, dropsy appear around the karyons;collagenous fiber between the liver cells hyperplasia. Conclusion:INH, RFP and PZA can lead to the damages of hepatic tissue, especially in the usage of multiple drugs;the degree of hepatic injury is increased with the numbers of drugs used;the toxicity of PZA on liver is greater than that of other antitubercular drugs.%目的：以透射电镜观察不同抗痨药物对SD大鼠肝脏超微结构的影响.方法：健康成年SD大鼠(清洁级)152只,体重250~300g,雌雄各半,随机分为8组.观察组：H组：异烟肼(INH H)；R组：：利福平(RFP R)；Z组：吡嗪酰胺(PZA Z)；HR组：异烟肼+利福平；HZ组：异烟肼+吡嗪酰胺；RZ 组：利福平+吡嗪酰胺；HRZ 组：异烟肼+利福平+吡嗪酰胺.对照组：生理盐水.大鼠用药剂量为人每公斤体重常用剂量的5.5倍.标本制备：每天对各组大鼠进行一次灌胃,10天后处死大鼠,分离肝脏,戊二醛固定后做电镜观察.结果：肝细胞部分线粒体溶解,粗面内质网脱颗粒,滑面内质网池扩张,细胞内脂肪颗粒增多,糖原颗粒显著增多；细胞核周水肿；肝细胞间胶原纤维增生.结论：异烟肼、利福平、吡嗪酰胺均可引起大鼠肝脏的损害,多种药物联用比单药应用损害更明显；随着药物应用种类的增多,肝脏损害逐渐加重；吡嗪酰胺组比其他单用药组肝脏毒性更大.