五脏温阳化瘀汤对动脉粥样硬化大鼠JAK2/STAT3信号转导及IL-6/STAT3信号通路影响

Effect of Wuchang Wenyang Huayu Decoction on JAK2/STAT3 Signal Transduction and IL-6/STAT3 Signaling Pathway for Atherosclerotic Rats

目的:分析五脏温阳化瘀汤对动脉粥样硬化(AS)大鼠JAK2/STAT3信号传导及IL-6/STAT3信号通路影响。方法:选取SPF级Wistar雄性大鼠45只,随机数字表法将大鼠分成3组,正常组、模型组与观察组,观察组与模型组制备AS模型,造模后观察组灌胃2ml/kg的五脏温阳化瘀汤药液,模型组与正常组则灌胃等剂量生理盐水,共进行6周。观察组大鼠腹主动脉病理状况,ELISA检测血清IL-6、SOCS、JAK2、STAT3、p-JAK2及p-STST3含量,实时荧光定量PCR检测各组大鼠肝脏组织内TLR4、NF-B、p38MAPK、IL-6、SOCS3、STAT3及JAK2mRNA表达。结果:和正常组相比,模型组组大鼠血清IL-6、SOCS3、STAT3及JAK2含量上升;和模型组相比,观察组大鼠血清IL-6SOCS3、STAT3及JAK2含量下降,差异均有统计学意义(P<0.05);和正常组相比,模型组大鼠血清p-STST3、p-JAK2、p-STAT3/STAT3及p-JAK2/JSK2含量上升;和模型组相比,观察组大鼠血清p-STST3、p-JAK2、p-STAT3/STAT3及p-JAK2/JSK2含量下降,差异均有统计学意义(P<0.05);和正常组相比,模型组大鼠肝脏内TLR4、NF-B、p38MAPK、IL-6、SOCS3、STAT3及JAK2mRNA表达上升;和模型组相比,观察组大鼠肝脏内TLR4、NF-B、p38MAPK、IL-6、SOCS3、STAT3及JAK2mRNA表达下降,差异均有统计学意义(P<0.05)。结论:五脏温阳化瘀汤经过抑制p38MAPK和JAK磷酸化,降低TLR4mRNA水平,减少IL-6分泌量,对JAK2/STAT3信号传导路径产生影响,改善AS大鼠症状。

Objective:To analyze the effect of Wuchang Wenyang Huayu Decoction on JAK2/STAT3 signal transduction and IL-6/STAT3 signaling pathway in atherosclerotic(AS)rats.Methods:A total of 45 male Wistar male rats were randomly divided into three groups:normal group,model group and observation group.The observation group and the model group were used to prepare AS model.After modeling,the observation group was intragastrically administered with 2 ml/kg of the five internal organs of Wenyang Huayu Decoction,the model group and the normal group were given the same amount of normal saline for 6 weeks.The pathological conditions of abdominal aorta in rats were observed.Serum levels of IL-6,SOCS,JAK2,STAT3,p-JAK2 and p-STST3 were detected by ELISA.TLR4,NF-B,P38MAPK,IL-6,SOCS3,STAT3 and JAK2 mRNA expression in liver tissues of rats in each group were detected by real-time fluorescent quantitative PCR.Results:Compared with the normal group,the serum levels of IL-6,SOCS3,STAT3 and JAK2 in the model group increased.Compared with the model group,the serum levels of IL-6,SOCS3,STAT3 and JAK2 in the observation group decreased.The difference was statistically significant(P<0.05).Compared with the normal group,the serum levels of p-STST3,p-JAK2,p-STAT3/STAT3 and p-JAK2/JSK2 in the model group increased;compared with the model group and the observation group,the serum levels of p-STST3,p-JAK2,p-STAT3/STAT3 and p-JAK2/JSK2 in the rats were significantly decreased(P<0.05).Compared with the normal group,the rats in the model group were TLR4 in the liver.NF-(B,p38MAPK,IL-6,SOCS3,STAT3 and JAK2mRNA expression increased.Compared with the model group,the liver of the observation group was TLR4,NF-(B,p38MAPK,IL-6,SOCS3,STAT3 and the expression of JAK2 mRNA decreased,and the difference was statistically significant(P<0.05).Conclusion:Wuji Wenyang Huayu Decoction can inhibit p38MAPK and JAK phosphorylation,decrease TLR4mRNA levels,decrease IL-6 secretion,and affect the JAK2/STAT3 signal transfer pathway,improving the symptoms of AS rats.