大黄不同炮制品对阿托伐他汀的增效减毒作用

目的探究大黄不同炮制品对阿托伐他汀(ATS)的增效减毒作用。方法通过人肝脏L02细胞实验考察生、酒、熟大黄提取物与ATS联用后的保肝作用,从中筛选出二者联用后保肝作用最优的炮制品提取物。通过人肝癌Hep G2细胞实验确定该炮制品提取物的有效调脂剂量范围;基于SD大鼠高脂血症模型,通过测定血脂和转氨酶水平、相关氧化应激参数,检测肝脏组织病理切片对最优提取物和ATS联用的调脂和保肝作用进行整体评价。结果 3种大黄炮制品中酒大黄醇提物可显著提高L02细胞存活率,对ATS所致L02细胞损伤的保护效果最好;同时酒大黄醇提物也可有效降低Hep G2细胞内总胆固醇(TC)和三酰甘油(TG)水平;ATS与酒大黄醇提物的保肝配比和调脂配比(质量比)分别为1∶6.7～1∶9.0和1∶35.8～1∶71.6。酒大黄醇提物与ATS联用后可降低高脂血症大鼠的血脂水平和肝脏中脂质含量;使大鼠血清中丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平显著降低,肝脏中超氧化物歧化酶(SOD)活力显著增强,丙二醛(MDA)水平显著降低;且高剂量酒大黄醇提物与ATS联用组可显著抑制炎细胞浸润和胆管增生。结论酒大黄醇提物能显著改善ATS引发的肝功能损伤,而且能增强ATS对高脂血症大鼠的调脂治疗效果,发挥减毒增效的作用。

Study on efficacy-enhancing and toxicity-reducing of different rhubarb processed products combined with atorvastatin

Objective To explore the effect of different processed products of rhubarb combined with atorvastatin (ATS) on the efficacy-enhancing and toxicity-reducing. Methods L02 cells were used to investigate the hepatoprotective effects of raw rhubarb, wine-fried rhubarb and wine-steamed rhubarb in clinical application combined with ATS, and the extracts of the processed products with the best liver protection were screened out. The effective lipid-lowering dose range of the extract of the processed product was determined by HepG2 cell experiments; Finally, based on the model of hyperlipidemia in SD rats, the lipid-lowering and hepatoprotective effects of the optimal extract and ATS were generally evaluated by measuring the blood lipid and transaminase levels and related oxidative stress parameters, detecting the histopathological section of the liver. Results The alcohol extract of wine-fried rhubarb in the three processed artillery products significantly improved the survival rate of L02 cells, and had the best protection effect on L02 cells induced by ATS. At the same time, the wine-fried rhubarb ethanol extract also effectively reduced the content of TC and TG in HepG2 hepatic steatosis cells. The liver-protection ratio and lipid-lowering ratio (mass ratio) of ATS to wine-fried rhubarb ethanol extract were 1:6.7-1:9.0 and 1:35.8-1:71.6. The wine-fried rhubarb ethanol extract and ATS reduced the blood lipid level and lipid content in the liver of hyperlipidemia rats; The serum levels of ALT and AST were significantly decreased, the SOD activity in the liver was significantly enhanced, and the MDA content was significantly reduced; And high-dose wine-fried rhubarb ethanol extract and ATS combination group significantly inhibited inflammatory cell infiltration and bile duct hyperplasia. Conclusion The combination of wine-fried rhubarb ethanol extract and ATS can significantly improve the liver function damage caused by ATS, enhance the effect of lipid-lowering therapy on hyperlipidemic rats, and play a role in reducing toxicity and increasing efficiency.