摘要
目的 基于细胞焦亡与中性粒细胞胞外诱捕网(NETs)探讨刺梨根对溃疡性结肠炎(UC)大鼠的影响.方法 将大鼠随机分为正常组和造模组,造模组给予三硝基苯磺酸(TNBS)/乙醇联合灌肠建立UC大鼠模型.将造模成功的大鼠随机分为模型组、柳氮磺吡啶组(0.3 g/kg)和刺梨根低、中、高剂量组(2、4、8 g/kg),各组灌胃给予相应药物.给药 21d后,计算疾病活动指数(DAI)评分,HE染色观察结肠组织病理改变,ELISA法检测血清白细胞介素(IL)-18、IL-1β 和髓过氧化物酶(MPO)水平,Western blot 及免疫组化法检测结肠组织 NE、MPO、NLRP3、caspase-1、GSDMD蛋白表达.结果 与正常组比较,模型组DAI评分升高(P＜0.01),血清IL-1β、IL-18、MPO水平升高(P＜0.01),结肠组织NE、MPO、caspase-1、NLRP3、GSDMD蛋白表达升高(P＜0.01);与模型组比较,柳氮磺吡啶组和刺梨根中、高剂量组DAI评分降低(P＜0.05,P＜0.01),血清IL-1β、IL-18、MPO水平降低(P＜0.01),结肠组织NE、MPO、caspase-1、NLRP3、GSDMD蛋白表达降低(P＜0.05,P＜0.01).结论 刺梨根可能通过调控细胞焦亡及NETs缓解UC大鼠炎症反应,改善结肠病理损伤.
Abstract
AIM To explore the effects of Rosa roxburghii Radix on ulcerative colitis(UC)in rats based on pyroptosis and neutrophil extracellular traps(NETs).METHODS Rats were randomly divided into the normal group and the model group.The successfully established UC rat models by trinitrobenzene sulfonic acid(TNBS)/ethanol enema were then randomly divided into the model group,the sulfasalazine group(0.3 g/kg)and the low,medium and high dose R.roxburghii Radix groups(2,4,8 g/kg),followed by dosing of corresponding drugs by gavage.21 days later,the rats had their disease activity index(DAI)score calculated;their pathological changes of colon tissue observed by HE staining;their levels of serum interleukin(IL)-18,IL-1β and myeloperoxidase(MPO)detected by ELISA;and their protein expressions of NE,MPO,NLRP3,caspase-1 and GSDMD in colon tissue detected by Western blot and immunohistochemistry.RESULTS Compared with the normal group,the model group displayed increased DAI score(P＜0.01),increased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and increased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.01).Compared with the model group,the groups intervened with sulfasalazine,or medium,or high dose R.roxburghii Radix demonstrated with decreased DAI scores(P＜0.05,P＜0.01),decreased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and decreased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.05,P＜0.01).CONCLUSION R.roxburghii Radix may alleviate the inflammatory reaction in a rat model of UC and improve its pathological injury of colon via regulating pyroptosis and NETs.
基金项目
国家重点研发计划(2019YFC1712501)
贵州省科技计划(黔科合后补助[2020]3003)
滚动支持省属高校科研平台团队项目(黔教技[2022]023)
维普
万方数据