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-l 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 lipids[totalcholesterol(TC),triglyceride(TG),low density lipoprotein(LDL)and high density lipoprotein(HDL)]and oxidative parameters[malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)]were measured by reagent kit.Nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase l(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.Keapl 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.
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