柚皮苷通过抑制CYP450基因表达保护药物所致HL-7702细胞

Protective effect of naringin on drug-induced HL-7702 cells by inhibiting CYP450 gene expression

目的探讨肝爽颗粒主要成分柚皮苷是否具有预防药物性肝损伤的功能以及保护作用的机制。方法选取具有肝毒性的药物(曲格列酮和双氯芬酸钠)制造体外模型,预防性地应用不同浓度的柚皮苷,通过半数抑制率(IC50)、转氨酶水平、乳酸脱氢酶水平、Caspase3基因水平评价HL-7702细胞的损伤情况。评价不同浓度的柚皮苷对细胞色素P450(CYP450)家族基因的改变情况。结果柚皮苷能够明显升高曲格列酮和双氯芬酸钠的IC50,具有降低转氨酶、Caspase3表达的作用。但这种改善具有剂量依赖性,其中100μmol/L柚皮苷的保护作用最明显,1μmol/L柚皮苷和10μmol/L柚皮苷的保护作用不明显。比较CYP代谢酶基因改变情况发现,100μmol/L柚皮苷能明显抑制其表达(P<0.05),1μmol/L柚皮苷和10μmol/L柚皮苷的抑制作用不明显。结论肝爽颗粒主要成分柚皮苷能够通过抑制CYP450酶的功能,从而起到预防作用。

Objective To investigate whether naringin,the main component of Ganshuang granule,has the function of preventing drug-induced liver injury (DILI) and its mechanism. Methods Drugs (Trioglitazone and Diclofenac sodium) were selected to make the hepatotoxicity model in vitro.Different concentrations of naringin were used preventively.Half inhibitory concentration (IC 50 ),transaminase level,lactate dehydrogenase level and Caspase3 level were used to evaluate the damage of HL-7702 cells.The changes of cytochrome P450 (CYP450) family genes in different concentrations of naringin were evaluated. Results Naringin could significantly increase the levels of IC 50 of Trioglitazone and Diclofenac sodium,and decrease the expressions of transaminase and Caspase3.But this phenomenon was dose dependent.The protective effect of 100 μmol/L naringin was obvious,but the protective effects of 1 μmol/L naringin and 10 μmol/L naringin were not obvious.The gene changes of CYP450 enzymes were compared,100 μmol/L naringin could significantly inhibit the expression of CYP450,but 1 μmol/L naringin and 10 μmol/L naringin could not. Conclusion Naringin,the main component of Ganshuang granule,can prevent DILI by inhibiting the gene expression of CYP450 enzyme.