醋甘遂与炙甘草免煎颗粒配伍对CYP2E1、CYP3A4基因和蛋白表达的影响

发布时间：2019-04-30 12:42

【摘要】：目的:通过检测大鼠肝功能指标和肝组织CYP2E1、CYP3A4的基因、蛋白表达,初步观察醋甘遂与炙甘草配伍对肝脏的损伤以及对肝药酶2个亚型的诱导作用。方法:将大鼠按体质量随机分为正常组、炙甘草组(免煎颗粒剂)、醋甘遂组(研末)、炙甘草-醋甘遂组、甘遂半夏汤组。其中正常组给予生理盐水灌胃,其余各组给予相应药液灌胃,连续给药14天。实验结束时,腹主动脉取血分离血清和血浆检测谷草转氨酶(AST)、谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)含量;取肝组织一部分用福尔马林固定观察肝组织病理形态,一部分液氮冻存,采用RT-PCR和western-blot技术检测肝组织中CYP2E1、CYP3A4的基因、蛋白表达情况。结果:与正常组相比,各给药组ALT含量各组变化不明显,无统计学差异(P0.05),AST含量甘遂组以及醋甘遂-炙甘草配伍组、甘遂半夏汤组较正常组降低,其中甘遂半夏汤组降低显著,有统计学差异(P0.05),LDH含量各给药组均较正常组显著降低,有统计学差异(P0.05,P0.01)。与空白组比较,炙甘草组、醋甘遂组、醋甘遂-炙甘草组和甘遂半夏汤组CYP2E1基金和蛋白表达均有所升高,CYP3A4的基因和蛋白表达则有所下降,二者均具有统计学差异(P0.01),其中以醋甘遂-炙甘草组升高或降低最为明显;与醋甘遂-炙甘草组比较,甘遂半夏汤组下调CYP2E1基金和蛋白表达,上调CYP3A4的基因和蛋白表达。结论:本实验从分子机制上证实了醋甘遂和炙甘草配伍有增毒效应,以复方的形式使用则能降低毒性,但在生化指标方面未表现出明显增毒作用,可能还存在其他配伍机制有待进一步研究,且需要配合病理状态的研究以确定是否有增效作用。
[Abstract]:Aim: to detect the liver function index and the expression of CYP2E1,CYP3A4 gene and protein in liver tissue of rats, and to observe the liver damage induced by the combination of Radix Glycyrrhizae Sinensis and the induction of two subtypes of hepatic drug enzyme. Methods: rats were randomly divided into three groups according to their body weight: normal group, broiled glycyrrhizin group, vinegar-Gansui group and Gansui Banxia decoction group. The normal group was given saline intragastric administration, the other groups were given the corresponding drug solution, and the other groups were administered continuously for 14 days. At the end of the experiment, the serum and plasma were collected from abdominal aorta to detect the content of (AST), (ALT), LDH (LDH). Part of the liver tissue was fixed with formalin to observe the pathological morphology of liver tissue, and part of the liver tissue was frozen with liquid nitrogen. RT-PCR and western-blot techniques were used to detect the expression of CYP2E1,CYP3A4 gene and protein in the liver tissue. Results: compared with the normal group, the content of ALT in each group was not significantly changed, and there was no statistical difference (P0.05), AST content in Gansui group and the combination group of vinegar and Gansui-fried licorice, and the content of Gansui Banxia decoction group was lower than that in normal group. Gansui Banxia decoction group decreased significantly (P0.05), LDH content was significantly lower than the normal group, there was statistical difference (P0.05, P0.01). Compared with the blank group, the expression of CYP2E1 fund and protein in the grilled licorice group, vinegar Gansui-fried licorice group and Gansui Pinellia decoction group were increased, while the expression of CYP3A4 gene and protein were decreased, the difference was statistically significant (P0.01). Among them, the increase or decrease was the most obvious in the vinegar kansui-broiled glycyrrhizae group. Compared with the vinegar gansui-fried licorice group, Gansui Banxia decoction group down-regulated the expression of CYP2E1 fund and protein, and up-regulated the expression of CYP3A4 gene and protein. Conclusion: the experiment confirmed that the combination of vinegar and licorice could increase toxicity in molecular mechanism, but it could reduce toxicity in the form of compound prescription, but there was no obvious toxic effect in biochemical index, but there was no obvious toxic effect in biochemical index, but there was no obvious toxic effect in combination with Fructus Glycyrrhizae. There may be other compatibility mechanisms to be further studied, and it is necessary to cooperate with the pathological study to determine whether there is synergistic effect.
【作者单位】：河北中医学院;
【基金】：国家自然科学基金青年基金项目(81503268) 河北省中医药管理局项目(2015001) 河北省大学生创新创业训练计划项目(201414432022)
【分类号】：R285.5

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