Mechanism Of Sinomenine In Anti-atherosclerosis Inflammatory Response TLR4/NF-κB Pathway

Objective: to observe the effect of sinomenine injection on the expression of inflammatory factors in TLR4 / NF-κB signaling pathway in the course of anti-atherosclerosis,so as to provide the basic theory for the prevention and treatment of atherosclerosis by sinomenine injection.Methods: thirty-two New Zealand healthy rabbits were randomly divided into 4 groups:sinomenine group,Atto vastatin calcium group,blank control group and model control group,each group was divided into 4 groups: sinomenine group,Atto vastatin calcium group,blank control group and model control group.Rabbits in blank control group were fed with normal diet,model control group,sinomenine group and Atto vastatin calcium group were fed with high fat diet.From the first week of the experiment,Atto vastatin calcium group was fed with high fat diet and Atto vastatin calcium suspension 1.1mg/kg/d was given intraperitoneally,and sinomenine group was given high fat diet and sinomenine injection 40mg/kg/d intraperitoneally.At the end of the experiment,the animals were killed by the method of blood sampling and the samples were collected for the detection of the related indexes.The pathomorphological changes of rabbit aortic arch atherosclerosis were observed by HE staining in pathological sections,the weight of rabbits was measured by weighing method.The expression and level of TLR4,IKBa,NF-κ B protein in carotid artery were detected by western blot combined with image j image analysis.Results: 1)Sinomenine energy efficiency inhibited the weight gain induced by high fat diet in rabbits;2)the results of HE staining of rabbit aortic arch showed that the intima of rabbit aortic arch in blank control group was smooth and smooth,without lipid deposition and atherosclerotic plaque,without lumen stenosis and inflammatory infiltration.In the model group,obvious plaque formation,lumen stenosis,necrosis and disintegration products containing a large number of cells and other substances under the fibrous cap,cholesterol crystallization(acicular space),calcium deposition,and accumulation of foam cells were observed in the aortic arch of the rabbits in the model group.Smooth muscle cells were disarranged and the media was thinned due to plaque compression and destruction of elastic fibers.Compared with the model group,the inflammatory infiltration,lumen stenosis and smooth muscle cell arrangement were improved significantly in the Atto vastatin calcium group and sinomenine group.3The results of)Western blot showed that the expression of TLR4,NF-κB protein in the model control group was significantly higher than that in the blank control group,and the expression of TLR4,NF-κB protein in the Atto vastatin calcium group and sinomenine group was significantly lower than that in the model control group.Compared with the blank control group,the expression of IKBaprotein in the model control group was significantly lower than that in the model control group,while the expression of IKBa protein in the Atto vastatin calcium group and sinomenine group was significantly higher than that in the model control group.Conclusions: 1.Sinomenine injection can improve the pathological injury of aortic arch in atherosclerotic rabbits and effectively inhibit the weight gain induced by high-fat diet in rabbits.Sinomenine injection can promote the expression of IKBa,down-regulate the expression of TLR4,NF-κB protein and alleviate the inflammatory reaction in rabbits with AS.Activation of TLR4 / NF-κ B signaling pathway in atherosclerotic rabbits can be inhibited by sinomenine.It may be one of the mechanisms of preventing and treating AS by inhibiting the process of atherosclerosis.