钙拮抗剂治疗肝纤维化的亚细胞学研究

The subcellular study of calcium antagonists in treatment of hepatof ibrosis

目的 从亚细胞水平评价钙拮抗剂(Ca-A)抗鼠肝纤维化的作用。 方法 用40％CCl_4 0.5ml/只,SC,1次/3d,共15次,诱发Wistar大鼠肝纤维化。用不同剂量的4种Ca-A汉防已甲素(Tet)、维拉帕米(Ver)、硝苯啶(Nif)及脑益嗪(Cin)分别进行早、晚期治疗。分离制备线粒体及其内膜,检测单胺氧化酶(MAO)、N-乙酰β-D氨基葡萄糖苷酶(NAG)的活性和线粒体内膜表层及脂双层中心处的流动性。 结果 小剂量Tet能明显降低早期和晚期MAO及NAG活性,并增加线粒体内膜表层及脂双层中心处的流动性,与CCl_4造型组比较差异显著(P<0.05-0.01)。其它3种Ca-A的效果不尽一致。 结论 小剂量Tet具有良好的抗肝纤维化作用。

AIMS The effects of calcium antagonists (Ca-A) on hepatofibrosis of rats were studied in subcellular level.METHODS Hepatofibrosis model was induced in Wistar rats with 40% CC14 0.5 ml/per rat SC, once every three days for 15 times. Then different doses of tetrandrine, verapamil, nifedipine and cin-narizine were used to treat these rats in the early and late hepatofi-brotic stages. Mitochondria and inner membrane were separated, MAO and N-acety β-glucosaminidase ( NAG ) activities were assayed, and mitochondrial inner memeberane superfical and para-central fuidities were detected.RESULTS Small dose of tetrandrine not only decrease MAO and NAG activities of early and late treatment groups, but also increase mitochondrial inner membrane superfical and paracentral fluidities, compared with CC14 model group(P<0.05-0.001). Other three Ca-A had different effects.CONCLUSIONS Small dose of tetrandrine has the best action of anti-hepatofibrosis.