Study on Mechanism of the Improvement Effects of Xinmaikang on Atherosclerosis in Rabbits Based on TLR 4/ NF-κB Signaling Pathway / 中国药房

ABSTRACT

OBJECTIVE：To explore t he mechanism of Xinmaikang improving atherosclerosis （AS）in rabbits. METHODS ：A total of 50 male Zealand rabbits were randomly divided into sham operation group ，model group ，simvastatin group [positive control ， 2.60 mg/（kg·d）] and Xinmaikang low-dose and high-dose groups [ 0.21，0.84 g/（kg·d）]，with 10 rabbits in each group. Rabbits in sham operation group were fed with ordinary diet ，and only femoral artery was separated and ligated ，and abdominal aortic endothelium was not strained ；the other groups were given high-fat diet and received abdominal aortic intimal balloon injury to induce AS model. Ten weeks after operation ，sham operation group and model group were given intragastric administration of normal saline ，and administration groups were given corresponding drug solution intragastrically （normal saline as solvent ）with the volume of 100 mL，once a day ，for consecutive 12 weeks. After last administration ，the pathological changes of abdominal aorta and inner wall in rabbits were observed in each group. The serum contents of triglyceride （TG），total cholesterol （TC），low density lipoprotein cholesterol （LDL-C），high density lipoprotein cholesterol （HDL-C），interleukin-6（IL-6）and IL- 1β were detected，and the contents and protein expression of Toll-like receptor 4（TLR4）and nuclear factor-κB p65（NF-κB p65）in abdominal aortic tissue were determined. RESULTS ：Compared with sham operation group ，the intima of abdominal aorta in model group was rich in lipids ，the thickness of vessel wall and plaque area were increased obviously ，and there was obvious vascular endothelial injury. The contents of TG ，TC，LDL-C，IL-6 and IL- 1β in serum，the contents and protein expression of TLR 4 and NF-κB p65 in abdominal aorta tissue were significantly increased ，while the content of HDL-C was decreased significantly （P＜0.05 or P＜ 0.01）. Compared with model group ，the lesion of rabbit abdominal aorta were alleviated ，and no obvious damage was found on the inner wall. The contents of TG ，TC，LDL-C，IL-6，IL-1β of Xinmaikang high-dose group and simvastatin group as well as the content of NF-κB p65 and protein expression of TLR4 and cnd- NF-κB p65 were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：Xinmaikang can improve AS in rabbits ， and its mechanism may be assicated with inhibiting the expression of TLR 4，NF-κB p65 and inhibiting inflammatory response.