藏药三果汤调节Nrf2/HO-1信号通路干预高脂血症大鼠的作用机制

目的 基于Nrf2/HO-1信号通路探讨藏药三果汤对高脂血症大鼠保护作用及相关作用机制。方法 雄性SD大鼠48只，随机分为6组，即正常对照组、模型对照组、辛伐他汀组(3.5 mg·kg^-1)，藏药三果汤低、中、高剂量组(0.43,0.86,1.72 g·kg^-1)，每组8只。正常对照组给予基础饲料喂养，其余各组给予H10060高脂饲料喂养，制备高脂血症大鼠模型，造模的同时，各给药组每天1次给予相应药物灌胃，正常对照组、模型对照组给予等体积的生理盐水(1次·d-1)，连续灌胃6周。实验期间每周固定时间称取各组大鼠体质量1次，6周后试剂盒检测血清中血脂总胆固醇(totalcholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)]及氧化指标丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathio...

Mechanism of Tibetan Medicine Sanguo Decoction Prevent High-Fat Diet-induced Hyperlipidemia Rats by Regulating Nrf2/HO-1 Signal Pathway

OBJECTIVE To investigate the protective effect of Tibetan medicine Sanguo decoction on hyperlipidemic rats based on the Nrf2/HO-1 signaling pathway and its related mechanisms. METHODS Forty-eight male SD rats were randomly divided into six groups: the normal control group, the model control group, the simvastatin group(3.5 mg·kg^-1), and the Tibetan medicine Sanguo decoction low, medium, and high dose groups(0.43 , 0.86 , 1.72 g·kg^-1), with eight rats in each group. The normal control group was fed a basal diet, and the remaining groups were fed the H10060 high-fat diet to prepare a hyperlipidemic rat model. At the same time, each treatment group was given corresponding drugs by gavage once a day. The normal control group and model control group were given an equal volume of physiological saline(once a day) by gavage for 6 consecutive weeks. After 6 weeks, serum levels of lipidstotalcholesterol(TC), triglyceride(TG), low density lipoprotein(LDL) and high density lipoprotein(HDL)] and oxidative parametersmalondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH)] were measured by reagent kit. Nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), Keap1, and quinone oxidoreductase(NQO1) protein expression in liver tissues were analyzed by Western blotting. The correlation of lipid and oxidative indices was investigated by person correlation. RESULTS Compared with the normal control group, the model control group showed a significant increase in body weight, significantly higher serum levels of TC, TG, LDL, and MDA, significantly lower serum levels of HDL, and significantly lower SOD and GSH activity. Compared with the model control group, each administration group showed a decrease in body weight and serum TC, TG, LDL, and MDA levels. In comparison with the model control group, the body weight was reduced, the serum levels of TC, TG, LDL, and MDA were significantly lower, the serum levels of HDL were significantly higher, and the SOD and GSH activities were significantly higher. Keap1 protein level expression was significantly up-regulated compared with the normal control group, and Nrf2, HO-1, and NQO1 protein level expression were significantly down-regulated in the model control group. Keap1 protein level expression was significantly down-regulated compared to the model control group, and Nrf2, HO-1, and NQO1 protein level expression were significantly up-regulated in the liver tissues of low and high doses of Sanguo decoction. The expressions of Nrf2, HO-1, and NQO1 were significantly up-regulated. Correlation analysis showed that TG was negatively correlated with SOD, HO-1, and NQO1, and positively correlated with Keap1, while TC was negatively correlated with SOD, HO-1, GSH, and Nrf2, and positively correlated with Keap1 and MDA. CONCLUSION The Tibetan medicine Sanguo decoction can improve body weight and blood lipid levels in hyperlipidemic rats, and the mechanism may be related to the regulation of the Nrf2/HO-1 signaling pathway and the improvement of oxidative stress.