健脾益肠散对溃疡性结肠炎大鼠NLRP3信号通路IL-1β、IL-18表达的影响

Effects of Jianpi Yichang Powder on Expressions of IL-1βand IL-18 of NLRP3 Signaling Pathway in Ulcerative Colitis Rats

目的探讨健脾益肠散对溃疡性结肠炎(UC)模型大鼠NLRP3信号通路白细胞介素(IL)-1β、IL-18表达的影响。方法从40只SD大鼠随机选取10只作为正常组,其余大鼠自由饮用5%硫酸葡聚糖溶液7 d制备UC大鼠模型,将成模大鼠随机分为模型组、柳氮磺吡啶组和健脾益肠散组,每组10只。健脾益肠散组和柳氮磺吡啶组予相应药液灌胃,正常组和模型组予等体积蒸馏水灌胃,连续14 d。观察大鼠一般状况,并进行疾病活动指数(DAI)评分,ELISA检测大鼠血清核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶1(Caspase-l)含量,免疫组化染色、Western blot和RT-PCR检测结肠组织IL-1β、IL-18蛋白及mRNA表达。结果与正常组比较,模型组大鼠一般状况较差,DAI评分显著升高(P<0.01),血清NLRP3、ASC、Caspase-l含量显著增加(P<0.01),结肠组织IL-1β、IL-18蛋白和mRNA表达均显著升高(P<0.01);与模型组比较,健脾益肠散组和柳氮磺嘧啶组大鼠一般状况明显好转,DAI评分显著降低(P<0.01),血清NLRP3、ASC、Caspase-l含量明显减少(P<0.05,P<0.01),结肠组织IL-1β、IL-18蛋白和mRNA表达均明显降低(P<0.05,P<0.01)。结论健脾益肠散可抑制NLRP3信号通路IL-1β、IL-18表达,改善结肠免疫炎症损伤,发挥治疗UC作用。

Objective To explore the effects of Jianpi Yichang Powder on the expressions of interleukin(IL)-1βand IL-18 of NLRP3 signaling pathway in ulcerative colitis(UC)model rats.Methods Ten rats were randomly selected from 40 SD rats as the normal group,and the other rats freely drank 5%dextran sulfate solution for 7 days to replicate UC rats model.The model rats were randomly divided into model group,sulfasalazine group and Jianpi Yichang Powder group,with 10 rats in each group.Jianpi Yichang Powder group and sulfasalazine group were given corresponding liquid medicine for gavage,and the normal and model groups were given equivalent volume distilled water for gavage for consecutive 14 d.The general status was observed,and the disease activity index(DAI)was scored,the contents of NLRP3,apoptosis-associated spotted proteins(ASC),and Caspase-1 in serum were detected by ELISA,the expressions of IL-1βand IL-18 protein and mRNA in colon tissue were detected by immunohistochemistry,Western blot and RT-PCR respectively.Results Compared with the normal group,the general status of the rats in model group was relatively worse,and DAI score significantly increased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum were significantly increased(P<0.01),the expressions of IL-1βand IL-18 protein and mRNA in colon tissue were significantly increased(P<0.01).Compared with the model group,the general status of the rats in Jianpi Yichang Powder group and sulfasalazine group were significantly improved,DAI score significantly decreased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum significantly reduced(P<0.05,P<0.01),and the expressions of IL-1βand IL-18 protein and mRNA in colon tissue significantly decreased(P<0.05,P<0.01).Conclusion Jianpi Yichang Powder can inhibit IL-1βand IL-18 expression of NLRP3 signaling pathway to reduce colon immune inflammatory damage,thus play a role in treating UC.