蛋白酶激活受体-2激动药对重症急性胰腺炎大鼠肠道SIgA的影响

Effect of Protease Activated Receptor-2 Agonist on Intestinal SIgA in Rats with Acute Necrotizing Pancreatitis

目的研究重症急性胰腺炎(SAP)大鼠肠黏膜免疫屏障的变化及蛋白酶激活受体(PAR)-2激动药对其的影响。方法制备SAP大鼠模型,采用PAR-2激动药进行预处理,检测假手术组、模型组及预处理组造模后6,12,24 h大鼠小肠黏液分泌性免疫球蛋白A(SIgA),小肠组织病理学、小肠组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6。组间数据比较采用单因素方差分析,小肠组织TNF-α、IL-6与小肠黏液SIgA,小肠组织病理学评分之间的相关性采用线性相关分析。结果模型组与假手术组相比,随造模时间的延长,小肠黏液SIgA浓度降低,小肠组织病理学评分及小肠组织TNF-α、IL-6水平升高(P<0.05),预处理组与模型组相比,小肠黏液SIgA浓度升高,小肠组织病理学评分及小肠组织TNF-α、IL-6水平降低(P<0.05),小肠组织TNF-α、IL-6水平与小肠组织病理学评分具有明显的正相关(P<0.01),与小肠黏液SIgA之间具有明显的负相关(P<0.01)。结论 SAP大鼠早期即发生肠黏膜免疫功能下降,免疫屏障受损;SLIGKV-NH2预处理SAP大鼠后,能显著降低小肠局部主要炎症因子水平,改善肠黏膜免疫屏障损伤程度。

Objective To discuss the effects of proteinase-activated receptor-2 （PAR-2） agonists on intestinal SIgA levels in rats with severe acute necrotizing pancreatitis （SAP）. Methods This study established SAP rat model and observed the levels of TNF-α and IL-6 in intestinal mucosa, SIgA content in intestinal mucus and histopathological changes of intestinal mucosa 6,12, and 24 h after establishment of model. The univariate analysis was used to compare the difference among groups. Linear correlation analysis was used to compare correlation between inflammatory mediators （TNF-α, IL-6） and SIgA content in intestinal mucus, as well as the histopathological scores of intestinal mucosa. Results The level of TNF-α and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly increased but SIgA content was decreased in model group at each time point after establishment of model, as compared with the sham-operated group （P〈0.05）. The level of TNF-c~ and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly decreased while SIgA content in intestinal mucus increased in pretreatment group at each time point after establishment of model, as compared with the model group （P〈0.05）. There was a positive relationship between inflammatory mediators （TNF-α, 1L-6） in intestinal mucosa and histopathological scores of intestinal mucosa （ P〈0.01 ）. There was a negative relationship between inflammatory mediators （TNF-α,IL-6） and SIgA content in intestinal mucus （P〈0.05）. Conclusion Intestinal mucosa immune barrier was impaired in the early stage of SAP in rats. PAR-2 agonist has therapeutic effects on intestinal mucosa immune barrier,which is related to the inhibition of excessive release of inflammatory mediators （TNF-α and IL-6） in rats with SAP.