感染后肠易激综合征小鼠不同肠段肠黏膜热休克蛋白70的表达及意义

Role of differentially expressed heat shock protein 70 in various intestinal segments of mice in pathogenesis of post-infectious irritable bowel syndrome

目的探讨感染后肠易激综合征(PI-IBS)小鼠不同肠段肠黏膜热休克蛋白70(HSP70)的表达,及其与炎症细胞因子表达的相关性。方法旋毛虫感染小鼠,不同肠段肠黏膜组织苏木精-伊红染色法(HE)染色,炎症评分。腹壁撤退反射(AWR)和结肠传输试验(CTT)观察内脏敏感性和肠道动力变化。免疫组织化学及酶联免疫吸附试验(ELISA)检测不同肠段HSP70和炎症细胞因子的表达。Spearman相关性分析HSP70与炎症细胞因子表达的相关性。结果 1小鼠感染旋毛虫后末段回肠和结肠出现明显炎症,炎症消退后仍存在明显的内脏高敏感和肠道动力异常。2PI-IBS小鼠空肠和末段回肠的HSP70表达较对照组明显增强(P<0.01)。3PI-IBS小鼠末段回肠白细胞介素-17(IL-17)、干扰素-γ(IFN-γ)水平明显升高,空肠、末段回肠及结肠白细胞介素-10(IL-10)水平明显降低(P<0.01)。4PI-IBS小鼠空肠HSP70表达与炎症细胞因子IL-10呈负相关(P<0.01);末段回肠HSP70表达与IL-10呈负相关(P<0.01),与IL-17、IFN-γ呈正相关(P<0.01)。结论 1不同肠段HSP70和炎症细胞因子的相关差异性表达可能在PI-IBS发病中起作用。2末段回肠可能是PI-IBS最重要的炎症免疫启动和调控部位。

【Objective】 To elucidate the role of differentially expressed heat shock protein 70（HSP70） in various intestinal segments of mice in the pathogenesis of post-infectious irritable bowel syndrome（PI-IBS）.【Methods】 To establish the PI-IBS animal model, the mice were infected with Trichinella spiralis. After 8weeks, the intestinal inflammatory score, abdominal withdrawal reflex（AWR）, intestine transportation time and Bristol scores were used to evaluate the clinical features of the mice, which were regarded as the characteristics for IBS. The intestinal HSP70 level in the various bowel segments including jejunum, terminal ileum and colon was detected by immunohistochemistry. The concentration of the intestinal inflammatory cytokines was examined by ELISA. The relationship between the intestinal HSP70 level and the clinical features of PI-IBS was studied by Spearman correlation analysis. 【Results】 1 The infected mice showed remarkable visceral hypersensitivity and abnormal intestinal motility even after the significant inflammation disappeared in their terminal ileum and proximal colon. 2 The expression of HSP70 significantly increased in the jejunum and terminal ileum of the PI-IBS mice（P 〈 0.01） compared to the control group. 3 The expressions of IL-17 and IFN-γsignificantly increased in the terminal ileum of the PI-IBS mice（P 〈 0.01）, while that of IL-10 decreased in all the three intestine segments（P 〈 0.01）. 4 In jejunum and terminal ileum of the PI-IBS mice, there was a negative correlation between HSP70 level and IL-10（P 〈 0.01）, while there were positive correlations between HSP70 level and both IL-17 and IFN-γ in the terminal ileum（P 〈 0.01）. 【Conclusions】 1 The differentially expressed heat shock protein 70 in various intestinal segments may play an important role in the pathogenesis of post-infectious irritable bowel syndrome. 2 The terminal ileum may be an essential location where the inflammatory process, immune response and regulating events are triggered.