Studies On Effects And Mechanisms Of Ethanol Extracts Of Schisandrae Chinensis Against Atherosclerosis

Objective Studies on effects and mechanisms of ethanol extracts of Schisandrae Chinensis against atherosclerosis.Method The rat model of atherosclerosis was established by intraperitoneal injection with VD3 combined with high fat diet for 9 weeks.4mg/kg/d of simvastatin as a positive control,the rats were fed low dose(0.35g/kg/d),middle dose(0.7g/kg/d),high dose(1.4g/kg/d)ethanol extracts of Schisandrae Chinensis for 3 weeks.Double reagent was measured the content of TG,LDL-C,HDL-C in serum of rats;Micro-plate was measured the content of ALT,AST in serum;Eosin(HE)staining was observed the pathological changes of liver tissue and thoracic aorta;The glutathione peroxidase(GSH-PX),catalase(CAT),superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by biochemical assay to observe the effect on oxidative stress indicators.The expressions of nuclear factor E2-related factor 2(Nrf-2)and heme oxygenase-1(HO-1)were detected by immunohistochemical staining.ELISA was used to detect protein expression of oxidized low density lipoprotein(ox-LDL),endothelin-1(ET-1),thromboxane B2(TXB2),6-keto prostaglandin F1 alpha(6-keto-PGF1?),in order to explain the mechanism in treatment of atherosclerosis.Result The rat model of AS was successfully established.The aorta of rats in the model group showed obvious plaque,intimal thickening of the vessel wall,foam cells contained different amounts of plaque.Compared with the model control group,the intima,the medial membrane and the adventitia were observed in the arteries of ethanol extracts of Schisandrae Chinensis groups.The structure was relatively complete and the plaque formation was not obvious.The thickening of the intima,smooth muscle fiber lesions was lighter,the number of foam cells was decreased,the percent plaque area was decreased with the effect of inhibiting atherosclerosis.Histopathological observation of liver tissue showed that the liver cells of model control group were not obvious,the hepatic cord was disordered,and the vacuoles were enlarged in the cytoplasm.Compared with model control group,the high dose group had no obvious lesions in cytoplasmic vacuole and hepatic injury caused by atherosclerosis.Compared with the model group,simvastatin group,and alcohol extract of Schisandrae chinensis low dose group,middle dose group and high dose group can highly significantly reduce the content of TG(P<0.001)and significantly reduce the content of LDL-C(P<0.001 or P<0.01 or P<0.05).Middle dose group and high dose group can significantly increased the content of HDL-C in serum(P<0.01 or P<0.05);Ethanol extracts of Schisandrae Chinensis groups can significantly reduce ALT,AST inserum(P<0.001 or P<0.05 or P<0.01).The ethanol extracts of Schisandrae Chinensis groups can significantly reduce the content of the GSH-PX activity and decrease levels of MDA in serum(P<0.001),the low,middle dose groups can enhance the activity of CAT(P<0.001),and low dose group can enhance the activity of SOD(P<0.01).The mechanism of the further study showed that the ethanol extracts of Schisandrae Chinensis groups can significantly up-regulated the expression of Nrf-2(P<0.001).and high dose group can significantly up-regulated the expression of HO-1 in rat aortic(P<0.01).The ethanol extracts of Schisandrae Chinensis groups can significantly reduce decrease the expression of ox-LDL protein(P<0.01),up-regulated expression of 6-keto-PGF1?(P<0.001),low and medium dose group can inhibit ET-1 protein(P<0.01 or P<0.05),and each group had no significant effect on the expression of TXB2.Conclusion The ethanol extracts of Schisandrae Chinensis has positive effect on the treatment of atherosclerosis,and promote the regulation of lipid metabolism in rats.Its mechanism may be associated with the activation of Nrf-2/ARE pathway,inhibition of ox-LDL,ET-1 expression,and regulation the balance of TXB2/6-keto-PGF1?.The above mentioned results indicated that the ethanol extract of Schisandrae Chinensis can regulate the level of oxidative stress and maintain the function of endothelial cell to treat the atherosclerosis.