基于TRPV1调控内皮细胞炎症反应探讨人参汤治疗AS小鼠的作用机制OA

Objective:To investigate the mechanisms by which Renshentang treats atherosclerosis(AS)in mice,focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1(TRPV1).Methods:An AS model was established in apolipoprotein E knockout(ApoE-/-)mice fed a high-fat diet.The mice were randomly divided into a simvastatin group(0.02 g·kg-1·d-1)and low-,medium-,and high-dose Renshentang groups(1.77,3.54,7.08 g·kg-1·d-1),with 12 mice in each group.ApoE-/-mice were fed a high-fat diet and treated simultaneously.C57BL/6J mice fed a normal diet served as the normal group(n=9).After continuous administration for 12 weeks,mice were anesthetized and the aortas were collected.Oil Red O staining was used to observe lipid plaque formation in the aorta.Hematoxylin-eosin(HE)staining was performed to examine pathological changes in the aortic root.Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),as well as the expression of TRPV1,phosphorylated phosphoinositide 3-kinase(p-PI3K),and phosphorylated protein kinase B(p-Akt)in the aortic root.Real-time quantitative polymerase chain reaction(Real-time PCR)was used to detect endothelial nitric oxide synthase(eNOS)mRNA expression in the aorta,and Western blot was used to detect TRPV1 protein expression.Results:Compared with the normal group,the model group showed a significant increase in aortic plaque formation(P＜0.01)and significantly elevated levels of TNF-α and IL-1β in the aortic root(P＜0.01).The expression levels of TRPV1,p-PI3K,and p-Akt were decreased(P＜0.05,P＜0.01),and eNOS mRNA expression was reduced(P＜0.05,P＜0.01).Compared with the model group,all Renshentang groups significantly reduced aortic plaque formation(P＜0.01),significantly decreased TNF-α and IL-1β levels(P＜0.01),and markedly increased the expression levels of TRPV1,p-PI3K,p-Akt,and eNOS mRNA(P＜0.05,P＜0.01).Conclusion:Renshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway,which may be one of the molecular mechanisms underlying its therapeutic effect against AS.