摘要
目的 通过脓毒症大鼠模型探讨IL-6/STAT3通路是否对高迁移率族蛋白(HMGB1)的表达起调控作用.方法 清洁级雄性SD大鼠120只,随机数字表法分为3组:假手术S组(n=40)、模型C组(n=40)和治疗T组(n=40).S组行单纯剖腹术,C组和T组分别用盲肠结扎穿孔术构建脓毒症大鼠模型.T组术后1 h腹腔注射抗IL-6单克隆抗体,S组和C组同时腹腔注射等量乳酸钠林格液.分别于术后3 h、12 h、24 h、48 h从三组各取10只大鼠,留取血浆和肠黏膜组织标本,采用HE染色光镜下观察肠黏膜损伤情况并进行病理评分;分光光度法测定血浆中二胺氧化酶(DAO)及D-乳酸含量;免疫组化法检测肠黏膜IL-6和HMGB1蛋白表达;Western-Blot检测p-STAT3表达情况.结果 C组和T组均可见不同程度的肠黏膜损伤,肠黏膜病理评分及DAO、D-乳酸在不同时间点均高于S组(P<0.05);且与S组相比,C组和T组小肠黏膜的IL-6、HMGBl及p-STAT3蛋白表达明显增加(P<0.05).T组与C组相比,肠黏膜损伤有明显改善,病理评分及血浆DAO、D-乳酸含量下降(P<0.05);IL-6、HMGBl及STAT3蛋白表达减低(P<0.05).小肠黏膜病理评分与IL-6和HMGB1蛋白表达在12 h、24 h、48 h存在显著正相关.结论 IL-6、HMGBl参与了脓毒症大鼠肠黏膜损伤,IL-6/STAT3信号通路可上调脓毒症大鼠肠黏膜组织HMGBl表达.
Objective To explore whether the IL-6/STAT3 signaling pathway regulate the expression of high mobility group proteins1 (HMGB1) in intestinal mucosa of rats with sepsis through the cecum ligation puncture (CLP). Methods One hundred and twenty male SD rats were randomly(random number) divided into three groups: sham operation group (group S, n=40), CLP group(group C, n=40) and anti-IL-6 monoclonal antibody group (group T, n=40). Rats in group S only received the simple laparotomy;Rats in group C and group T were established as a rat model of sepsis using CLP; rats in group T received the intraperitoneal injection of anti-IL-6 monoclonal antibody at 1 h after CLP, while the same volume of sodium lactate ringer's solution was injected to rats in group S and group C. Ten rats in each group were sacrificed at 3, 12, 24 and 48 h, respectively, and intestinal mucosa specimens were collected for pathological examinations by HE staining. The protein expression of HMGB1 and IL-6 were detected by immunohistochemistry, STAT3-protein by Western blot.and the levels of diamine oxidase (DAO) and D lactic acid in plasma by spectrophotometric. Results Rats in group C and group T showed obvious intestinal damage to different degrees, significantly higher intestinal mucosa pathological scores and plasma levels of DAO and D-lactic acid compared with rats in group S (P<0.05). The protein expression of IL-6, HMGBl and p-STAT3 of intestinal mucosa in group C and group T also significantly increased compared with that in group S (P<0.05). The intestinal mucosa pathological score, plasma levels of DAO and D-lactic acid and protein expression of IL-6, HMGBl and STAT3 were decreased in group T compared with those in group C (P<0.05). The intestinal mucosa pathological scores were positively correlated with the protein expression of IL-6 and HMGB1 at 12, 24, and 48 h, respectively. Conclusions IL-6 and HMGBl were involved in the intestinal injury of septic rats. IL-6/STAT3 signaling pathway could up-regulate the expression of HMGB1 in intesti
作者
胥朵
李建英
王小众
黄月红
陈林均
陈治新
Xu Duo;Li Jianying;Wang Xiaozhong;Huang Yuehong;Chen Linjun;Chen Zhixin(Union Clinical Medical College Affiliated to Fujian Medical University,Fuzhou 350001,China;Department of Respiration,Weinan Vocational Technical College)
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2018年第12期1360-1364,共5页
Chinese Journal of Emergency Medicine
基金
福建省自然科学基金资助项目(2015J01474)。
