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目的:评价黄芪甲苷对脓毒症小鼠肠屏障功能障碍的影响。方法:清洁级健康雄性C57BL/6J小鼠120只,6~8周龄,体重20~25 g,采用随机数字表法分为4组(n n=30):假手术组(SH组)、假手术+黄芪甲苷组(SH+A组)、脓毒症组(S组)、脓毒症+黄芪甲苷组(S+A组)。采用盲肠结扎穿孔(CLP)法制备小鼠脓毒症模型。SH+A组和S+A组分别于CLP术后1 h时尾静脉注射黄芪甲苷3 mg/kg,SH组和S组分别注射等体积二甲基亚砜。记录术后7 d各组小鼠的生存情况;于CLP术后24 h时心尖穿刺采集血样,采用ELISA法测定血清IL-1β和IL-18浓度;随后处死小鼠取小肠组织,采用ELISA法测定IL-1β和IL-18含量;采用HE染色法观察小肠组织病理学损伤并行Chiu评分;采用尤斯灌流仪检测小肠黏膜跨上皮电阻值(TER);分别采用Western blot法和RT-PCR法测定小肠组织NOD样受体家族3(NLRP3)、caspase-1及其mRNA的表达。n 结果:与SH组比较,S组和S+A组小鼠7 d生存率和TER降低,血清IL-1β和IL-18浓度、小肠组织Chiu评分、IL-1β和IL-18含量升高,NLRP3、caspase-1及其mRNA表达上调(n P<0.05);与S组比较,S+A组小鼠7 d生存率和TER升高,血清IL-1β和IL-18浓度、小肠组织Chiu评分、IL-1β和IL-18含量降低,NLRP3、caspase-1及其mRNA表达下调(n P0.05)。n 结论:黄芪甲苷可改善脓毒症小鼠肠屏障功能障碍,其机制可能与抑制NLRP3/caspase-1信号通路的激活,从而减轻炎症反应有关。“,”Objective:To evaluate the effect of astragaloside IV (AS-IV) on intestinal barrier dysfunction in septic mice.Method:One hundred and twenty clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups (n n=30 each) using a random number table method: sham operation group (group SH), sham operation plus AS-IV group (group SH+ A), sepsis group (group S), and sepsis plus AS-IV group (group S+ A). The model of sepsis was established by cecal ligation and puncture (CLP) in anesthetized mice.AS-IV 3 mg/kg was injected via the tail vein at 1 h after CLP in group SH+ A and group S+ A.The equal volume of dimethyl sulfoxide was injected instead in group SH and group S. The survival rate of mice in each group was recorded at 7 days after operation.Blood samples were collected from the cardiac apex at 24 h after CLP operation to measure concentrations of interleukin-1beta (IL-1β) and IL-18 in serum by enzyme-linked immunosorbent assay.Mice were then sacrificed, and intestinal tissues were removed to determine contents of IL-1β and IL-18 (by enzyme-linked immunosorbent assay), transepithelial electrical resistance (TER) (by Ussing chamber system), expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and caspase-1 protein and mRNA (by Western blot or real-time polymerase chain reaction) and to examine the pathological changes (using HE staining). Intestinal damage was assessed and scored according to Chiu.n Results:Compared with group SH, the 7-day survival rate and TER were significantly decreased, the concentrations of IL-1β and IL-18 in serum, Chiu′s score, contents of IL-1β and IL-18 were increased, and the expression of NLRP3 and caspase-1 protein and mRNA was up-regulated in group S and group S+ A (n P<0.05). Compared with group S, the 7-day survival rate and TER were significantly increased, the concentrations of IL-1β and IL-18 in serum, Chiu′s score, contents of IL-1β and IL-18 were decreased, and the expression of NLRP3 and caspase-1 protein and mRNA was down-regulated in group S+ A (n P0.05).n Conclusion:AS-IV can improve sepsis-induced intestinal barrier dysfunction in mice, and the mechanism may be related to inhibiting the activation of NLRP3/caspase-1 signaling pathway and thus reducing inflammatory responses.