Effect And Mechanism Of Gualou Xiebai Banxia Decoction On The Prevention And Treatment Of Atherosclerosis In Apoe-/- Mice

Objective:To study the different usage of Gualou Xiebai Banxia Decoction in treatment of ATH the difference and possible mechanism of action.Methods:Using high fat feed Apoe-/-mice(Apoe knockout mice)method to establish ATH model of 12 weeks,by detecting blood lipid four(TC,TG,LDLC,in HDLC),oil red O staining,HE staining to observe aorta plaque deposition and pathological changes of Elisa to detect serum TNF-α,1L-1β,1L-8,1L-6,MCP-1,NO,ET-1,Ang Ⅱ,OX-LDL,VCAM1,ICAM1,IHC was used to detect the expression levels of ALK1 and LDL in aorta,and Western Blot was used to detect the expression levels of ALK1 and LDL in aorta.Results:1.Model evaluation:10 weeks of high-fat feed mice aorta can be obviously red oil red O staining,HE sliced aortic intimal thickening,visible in the film shrinking,apparent plaques uplift,scattered foam cells can be seen in the plaque and fat cells,vascular smooth muscle cell morphological structure disorder,irregular arrangement.The morphology and structure of vascular smooth muscle cells in the blank group were normal,and no obvious pathological changes were observed.This indicates the successful establishment of atherosclerosis model.2.Blood lipid level:Compared with the blank group,the serum levels of TC,TG and LDLC in the model group were significantly higher than those in the normal control group(P<0.01),and the levels of HDLC were significantly lower in the model group(P<0.01).Compared with the model group,the levels of TC,TG and LDLC in the model group were significantly lower(P<0.01),and the levels of HDLC were significantly higher(P<0.01).In the Gushui group,TC level decreased(P<0.05),TG and LDLC significantly decreased(P<0.01),and HDLC level significantly increased(P<0.01).The HDLC level of the Xianjiu group was significantly increased(P<0.05),the LDLC level was significantly decreased(P<0.05),and the HDLC level of the Xianshui group was significantly increased(P<0.01).3.Morphological changes:HE staining showed slight lumps and plaques in the vascular intima,thickening of the middle membrane,normal vascular smooth muscle cells with clear boundaries and regular arrangement,mild inflammatory edema,exudated endothelial cells,and no foam cells.In the Gushui group,the intima was thickened,the plaques were raised and raised,the smooth muscle cells were disordered and irregularly arranged,there were scattered foam cells and inflammatory edema,and the lumen area was reduced.In the Xianjiu group,the intima and middle membrane of the blood vessel were thickened,the protruding fibers appeared,and the exudated cells were observed.A small amount of inflammatory infiltration was observed in the lumen,the cells were arranged irregularly,the structure was disordered,and the lumen area was relatively narrow.In the Xianshui group,the vascular intima was thickened and raised,with elevated plaques,fibrous tissue hyperplasia,and fibroblast formation,more foam cells,obvious inflammatory edema,and stenosis of lumen area.With oil red O staining,all groups of traditional Chinese medicine could significantly reduce the plaque area,and the effect of the Gujiu group was better than that of the other treatment groups(P<0.05).4.Elisa detection:Gualou Xiebai Banxia decoction in each treatment group can significantly improve the serumof TNF-α,1L-1 β,1L-8,1L-6,MCP-1,ET 1,Ang Ⅱ,OX-LDL,VCAM1,ICAM1 concentration decreased significantly,NO iecreased significantly(P<0.01).5.IHC detection:the positive expressions of ALK1 and LDL aorta were significantly decreased in the gujiu group,the gushui group and the present water group(P<0.01 or P<0.05),while the positive expressions of ALK1 and LDL aorta were decreased in the present wine group,but there was no statistical significance(P>0.05).WesternBlot detection:ALK1 protein expression in aorta of mice was down-regulated best in the present wine group,followed by that in the ancient water group.The effect of lowering the expression of LDL protein in the aorta of mice was the best in the gushui group,followed by the simvastatin group.Conclusion:Gualou xiebai banxia decoction can prevent ATH,reduce the levels of TC,TG and LDLC,improve the degree of vascular endothelial lesions,reduce the area of aortic plaque in mice,and effectively alleviate the development of ATH.The mechanism may be related to inhibiting the production of cytokines such as serum proinflammatory factors,chemokines and adhesion factors.Elevated serum NO concentration,reduce the serum levels of ET-1,Ang Ⅱ,OX-LDL concentration,to adjust the balance of contraction diastole factor,effectively protecting vascular endothelium,reducing oxidative damage,alleviate the vascular smooth muscle tension,improve blood vessel contraction diastole function disorder,adjust vascular endothelial dysfunction;The positive expression of ALK1 and LDL aorta was reduced,and the alkl-ldl pathway was inhibited,so as to improve the pathological process of ATH.The results showed that Gualou Xiebai Banxia decoction interfered with the occurrence and development of ATH,and had the characteristics of multi-target,multi-link and multi-path.In this study,the best effect of Gufang Jiujian group was obtained in Gujiu group>Gushui group>Xianjiu group>Xianshui group.