苦参碱微乳与苦参素胶囊对小鼠急性肝损伤保护作用的对比研究

Protective Effect of Matrine Microemulsion and Kushenin Capsule on Acute Hepatic Injury in Mice

关键词:  苦参碱  微乳  苦参素(氧化苦参碱)  CCl₄肝损伤

Key words:  matrine  microemulsion  kushenin(oxymatrine)  CCl₄ liver injury

摘要:

目的 观察苦参碱微乳经皮吸收制剂和口服苦参素胶囊对小鼠四氯化碳(CCl₄)肝损伤模型的保护作用，并比较两组之间的统计学差异。方法 将昆明种小鼠(60只)随机分为正常对照组、模型组、苦参素胶囊阳性对照组和苦参碱微乳制剂高、中、低剂量组。阳性对照组采用苦参素胶囊内容物水溶液(200 mg·kg^-1)预防性灌胃给药；苦参碱微乳制剂高、中、低剂量(200，100，50 mg·kg^-1)组预防性经皮给药；采用CCl4诱导小鼠急性肝损伤模型。测定各组血清丙氨酸转移酶(ALT)、天门冬氨酸氨基转移酶(AST)及肝组织匀浆超氧化物歧化酶(SOD)和丙二醛(MDA)的含量；取肝组织做病理学检测。结果 与模型组相比，苦参碱微乳高、中剂量组和苦参素胶囊水溶液组的ALT均显著降低(P<0.05)，肝组织匀浆中SOD含量明显升高(P<0.05)，MDA含量明显降低(P<0.05)，并减轻肝组织的病理变化。苦参碱微乳高剂量组和苦参素胶囊水溶液组的AST均显著降低(P<0.05)；苦参碱微乳制剂组ALT，AST水平及SOD，MDA含量以及病理变化与苦参素胶囊水溶液组间无显著性差异。结论 苦参碱微乳经皮给药对小鼠急性CCl4肝损伤具有保护作用，与临床用药苦参素胶囊比较无显著性差异。

Abstract:

OBJECTIVE To observe the protective effects of matrine microemulsion and kushenin capsule on acute hepatic injury by CCl₄ in mice, and compare the difference between the two groups. METHODS Kunming mice were separated into six groups randomly, including normal control group, model group, matrine microemulsion groups(high, medium and low-dose) and kushenin capsule positive control group. The mouse model of liver injury induced by CCl4. In order to prevent the liver injury, mouse were administered by transdermal delivery with the matrine microemulsion in high, medium and low dose (200, 100, 50 mg·kg^-1), and were administered by gavage with water solution of kushenin in 200 mg·kg^-1. After 14 days, the alanine transferase (ALT) and aspartate amino transferase (AST) in serum were determined, and the malondialdehyde (MDA) and superoxide dismutase (SOD) in liver homogenate were measured. The hepatic histological changes were observed with optical microscope. RESULTS Compared with the model group, ALT were significantly lower in the groups of high and medium doses of the matrine microemulsion and the group of water solution of kushenin(P<0.05), and the AST were significantly lower in the group of high doses of the matrine microemulsion and the group of water solution of kushenin(P<0.05). In addition, pre-treatment of matrine microemulsion significantly prevented the elevation of MDA formation and the depletion of SOD contents in the liver of CCl₄-injected mice (P<0.05), And it could ameliorate the hepatic pathological changes. The ALT, AST, MDA, SOD levels and pathological changes had no significant difference between the two groups of matrine microemulsion and water solution of kushenin. CONCLUSION Matrine microemulsion transdermal delivery played an important role in prevention of acute CCl4 liver injury in mouse. The protective effects on mouse model of liver injury by carbon tetrachloride had no significant difference between the two groups of matrine microemulsion and kushenin capsule.