| Peaonol has a good effect on rheumatoid arthritis,back and leg pain,stomach pain,eczema,allergic dermatitis,which is mainly used in the clinical treatment.In recent years,the anti-myocardial ischemia,anti-atherosclerosis and other cardiovascular pharmacological effects of Peaonol have gained an increasing attention.Atherosclerosis(AS)is one of the most common cardiovascular and cerebrovascular diseases,with coronary artery and cerebral atherosclerosis.The disease of atherosclerosis does great harm to human health,because it leads to luminal occlusion,wall rupture,bleeding,myocardial infarction,stroke and other serious consequences.Studies have shown that abnormal dyslipidemia,the body's inflammatory response and vascular endothelial dysfunction can lead to the occurrence of atherosclerosis.The preliminary study of this our research group found that,high fat serum can induce the proliferation of smooth muscle cells(SMC),and Peaonol has a significant inhibitory effect.Another study showed that Peaonol protects human umbilical vein endothelial cells(HUVECs)from high-fat injury and homocysteine injury.Moreover,its mechanism was related to the activation of endothelial cell nuclear factor-?B(NF-?B)and the expression of cell adhesion molecule(ICAM-1,VCAM-1).The effect of Peaonol on anti-AS and its mechanism that studied by cell culture can only explain its mechanism from the cellular level.In this study,we established the AS rat model by feeding high fat diet and intraperitoneal injection of vitamin D3.Compared with the cell culture,the establishment of AS rat model is closer to the pathogenesis of human disease.The effect of Peaonol on NF-?B signaling pathway,ICAM-1 and VCAM-1 expression in AS rats was not reported in domestic and foreign literatures.Therefore,we investigated the effect of Peaonol on NF-?B signaling pathway and the expression of ICAM-1,VCAM-1,chemokine MCP-1 and inflammatory factors CRP in AS rats to explore the mechanism of action of Peaonol against AS,and to provide experimental basis for the development and clinical application of Peaonol.Objective:To discuss the effect of Peaonol on coronary atherosclerosis inflammatory,analysis the mechanism by investigating the effects of Peaonol on blood lipid level,CRP level,NF-?B p65,ICAM-1,VCAM-1,MCP-1 protein and mRNA expression in AS rats.Methods:1 48 male SD rats were randomly divided into 6 groups: normal group(NC),model group(MD),Peaonol high and low dose group(Pae-H,Pae-M,Pae-L)Simvastatin group(XFTT),8 rats in each group.The normal group was given normal diet,model group and Peaonol groups were given high fat diet of 25 grams each for a week.Then they were given the intraperitoneal injection of vitamin D3 for 3 consecutive days.Peaonol groups were by gavage once,according to the corresponding dose.While the normal group and model group were given normal saline by gavage for 8 weeks.2 Automatic biochemical analyzer was used to detect TC,TG,LDL-C,HDL-C in rats.3 Pathological changes of aorta in rats were observed by HE staining.4 The content of ELISA was detected in serum of rats with CRP.5 RT-PCR method was used to test the mRNA expression of NF-?B p65?ICAM-1?VCAM-1?MCP-1 respectively.6 Western blotting method was used to detect the protein expression of NF-?B p65?ICAM-1?VCAM-1?MCP-1 respectivelyResults:1 The results of fat in serum.Compared with the normal group,the levels of TCL,TG,LDL-C and LDL-C/HDL-C in the model group were significantly higher than those in the normal group(P < 0.05),and the difference was statistically significant(P < 0.05),while the level of HDL-C decreased.Compared with the model group,the blood lipid indexes in Peaonol groups and simvastatin group also improved(P < 0.05).Compared with those in medium and low dose groups,TC,TG,LDL-C and LDL-C/HDL-C of high dose Peaonol group all increased,while HDL-C-C decreased.In the high dose Peaonol group and the simvastatin group,the lipid lowering effect was similar(P > 0.05).2 HE staining results.Observed arterial wall surface of normal group was smooth,while foam cells were found in the model group,which indicated atherosclerotic lesion.In the Peaonol group and simvastatin group,the pathological changes were alleviated,and the middle and low dose group of Peaonol was not as effective as the high dose group and simvastatin group.3 The detection results of CRP.Compared with the normal group,the content of CRP in plasma of model group increased(P < 0.05).Compared with the model group,the content of CRP in plasma of rats treated with Peaonol and simvastatin decreased in varying degrees(P < 0.05).Compared with the middle dose group and low dose group,the content of Peaonol in high dose group was lower(P < 0.05).The content of CRP in the high dose group was similar to that in simvastatin group(P > 0.05).4 The detection results of RT-PCR.Compared with the normal group,the content of mRNA of NF-?B p65,ICAM-1,VCAM-1 and MCP-1 in plasma of model group increased(P < 0.05).Compared with the model group,the content of mRNA in plasma of rats treated with Peaonol and simvastatin decreased in varying degrees(P < 0.05).Compared with the middle dose group and low dose group,the content of Peaonol in high dose group was lower(P < 0.05).The content of mRNA of NF-?B p65,ICAM-1,VCAM-1and MCP-1 in the high dose group was similar to those in simvastatin group(P > 0.05).5 The detection results of Western blotting.Compared with the normal group,the content of protein of NF-?B p65,ICAM-1,VCAM-1 and MCP-1 in plasma of model group increased(P < 0.05).Compared with the model group,the content of protein in plasma of rats treated with Peaonol and simvastatin decreased in varying degrees(P < 0.05).Compared with the middle dose group and low dose group,the content of Peaonol in high dose group was lower significantly(P < 0.05).The content of protein of NF-?B p65,ICAM-1,VCAM-1 and MCP-1 in the high dose group was similar to those in simvastatin group(P > 0.05).Conclusion:1 Peaonol can inhibit atherosclerosis by reducing the content of TC,TG,LDL-C and the LDL-C/HDL-C ratio and increasing the content of HDL-C in the high fat diet rats.2 Peaonol can reduce the expression of NF-?B p65 in the arterial tissue of rats with atherosclerosis and inhibit the excessive activation of NF-?B signaling pathway in rats with atherosclerosis.3 Peaonol can inhibit atherosclerosis by reducing the mRNAs and proteins expression of MCP-1,ICAM-1 and VCAM-1.4 Peaonol down-regulated the expression of ICAM-1,VCAM-1 by inhibiting NF-?B signaling pathway and then played a role of resistance to atherosclerosis probably. |
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