摘要
目的 探讨梓醇调节高迁移率族蛋白B1(HMGB1)-晚期糖基化终末产物受体(RAGE)信号通路对重症急性胰腺炎(SAP)大鼠肠道炎症的影响.方法 随机选取SD大鼠30只,其中6只大鼠作为假手术组(Sham组),其余24只大鼠通过注射牛磺胆酸钠溶液构建SAP大鼠模型.将SAP大鼠随机平分为SAP组、梓醇组(10 mg/kg梓醇)、右美托咪定(DEX)组(2.5 μg/kg HMGB1-RAGE 通路激活剂 DEX)、梓醇+DEX 组(10 mg/kg 梓醇+2.5 μg/kg DEX),每组均 6只大鼠.SAP组和Sham组给予等量生理盐水,给药时间分别为大鼠术后6 h、30 h,大鼠术后48 h后到达实验终点.ELISA法检测血清内毒素、二胺氧化酶(DAO)、D-乳酸以及肠道肿瘤坏死因子α(TNF-α)、白介素6(IL-6)水平;HE染色检测回肠组织病理学变化;Western Blot检测肠道屏障相关蛋白以及HMGB1-RAGE通路相关蛋白表达.结果 Sham组大鼠回肠黏膜和固有层正常且完整,与Sham组相比,SAP组大鼠回肠组织黏膜大量破坏,伴有较短、萎缩的绒毛,肠道评分、内毒素、D-乳酸、DAO、血清淀粉酶、IL-6、TNF-α、HMGB1、RAGE蛋白水平显著升高(P＜0.05),闭锁小带蛋白1(ZO-1)、闭锁蛋白(occludin)蛋白水平显著降低(P＜0.05).与SAP组相比,梓醇组大鼠回肠黏膜绒毛恢复,仅轻微水肿,黏膜完整性改善,肠道评分、内毒素、D-乳酸、DAO、IL-6、血清淀粉酶、TNF-α、HMGB1、RAGE蛋白水平显著减少(P＜0.05),ZO-1、occludin蛋白水平显著增加(P＜0.05),而DEX组以上指标结果与梓醇组趋势相反;DEX逆转了梓醇对SAP大鼠肠道炎症的治疗效果.结论 梓醇可能通过下调HMGB1-RAGE信号通路对SAP大鼠肠道炎症起到治疗作用.
Abstract
Objective To investigate the impact of catalpol on intestinal inflammation in rats with severe acute pancreati-tis(SAP)by regulating the high mobility group protein Bl(HMGB1)-receptor for advanced glycation end products(RAGE)sig-naling pathway.Methods 30 SD rats were randomly selected,with 6 rats serving as sham group,and the remaining 24 rats were injected with sodium taurocholate solution to establish an SAP rat model.SAP rats were randomly grouped into SAP group,catalpol group(10 mg/kg catalpol),dexmedetomidine(DEX)group(2.5 μg/kg HMGB1-RAGE pathway activator DEX),and catalpol+DEX group(10 mg/kg catalpol+2.5 μg/kg DEX),with 6 rats in each group.SAP group and sham group were given equal a-mounts of physiological saline once a day,administered at 6 h and 30 h postoperatively,respectively.Rats arriveded at the endpoint of the experiment after 48 h postoperatively.ELISA method was applied to detect serum endotoxin,diamine oxidase(DAO),D-lactate,and intestinal tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).HE staining was applied to detect pathological changes in the ileum tissue.Western Blot was applied to detect intestinal barrier related proteins and HMGB1-RAGE pathway relat-ed proteins.Results The ileal mucosa and lamina propria of rats in sham group were normal and intact.Compared with sham group,intestinal mucosa of rats in SAP group was extensively damaged,accompanied by shorter and atrophied villi,gut score,endo-toxin,D-lactate,DAO,amylase,IL-6,TNF-α,HMGBl,and RAGE proteins were obviously increased(P＜0.05).ZO-1 and occlu-din proteins were obviously decreased(P＜0.05).Compared with SAP group,the villi of the ileum mucosa in the catalpol group recovered,with only slight edema and improved mucosal integrity,gut score,endotoxin,D-lactate,DAO,amylase,IL-6,TNF-α,HMGB1,and RAGE proteins were obviously decreased(P＜0.05).ZO-1 and occludin proteins were obviously increased(P＜0.05).The above indicators in DEX group showed opposite trends to those in catalpol group.DEX reversed the therapeutic effect of catalpol on intestinal inflammation in SAP rats.Conclusion Catalpol may have a therapeutic effect on intestinal inflammation in SAP rats by down-regulating the HMGB1-RAGE signaling pathway.
维普
万方数据