Omega-3PUFAs通过p38MAPK通路参与重症胰腺炎肠道免疫功能调节及机制研究

The gut barrier immunosuppression induced by severe acute pancreatitis(SAP) can lead to intestinal bacteria/endotoxin translocation and sepsis. In SAP, mucosa ischemia caused by hypoxia usually makes suppression effects on lymphocyte proliferation and lymphocyte functions. As a therapeutic fatty acid, Omega-3 polyunsaturated fatty acids (PUFAs) can inhibit the damage of intestinal mucosa and maintain the physiological functions of gut immune barrier. The detailed mechanism of Omega-3 PUFAs in restoring gut immune barrier is still unclear. p38 MAPK is reported to be involved in regulating lymphocyte proliferation and differentiation, release of inflammatory mediators and lymphocyte homing. The immunoregulatory mechanism of Omega-3 PUFAs may be related to activation of p38 MAPK. In this study, we will evaluate the immunoregulatory effects of Omega-3 PUFAs in ischemia hypoxia model of human peripheral blood lymphocytes and SAP SD rat by using HE staining, ELISA, MTT, and Western Blot method, and clarify the possible mechanism of Omega-3 PUFAs.

重症胰腺炎(SAP)时肠黏膜免疫屏障破坏，常导致肠道细菌易位，引发脓毒症。ω-3PUFAs作为脂肪酸的一种，可保护肠粘膜屏障，抑制细菌易位，但具体机制不明。淋巴细胞是构成肠免疫屏障的重要组分，由于p38 MAPK参与调节淋巴细胞炎症介质产生，粘附分子表达及淋巴细胞增殖、分化过程，因此ω-3PUFAs的免疫调节作用可能与p38 MAPK通路相关。本研究运用原代淋巴细胞培养和SD大鼠SAP模型，采用HE染色病理评分、ELISA炎症介质检测、MTT法检测淋巴细胞增殖、以及Western-Blot法检测pp38活性，评价Omega-3PUFAs是否有益于促进缺血缺氧模型中淋巴细胞增殖、分化，维持淋巴细胞正常免疫功能，阐明Omega-3PUFAs 免疫调节作用与p38MAPK通路之间的关系，为进一步理解SAP肠损伤的机理以及临床预防和治疗肠道黏膜损伤提供重要的理论基础。

重症胰腺炎(SAP)时肠黏膜免疫屏障破坏，常导致肠道细菌易位，引发脓毒症。ω-3PUFAs作为 脂肪酸的一种，可保护肠黏膜屏障，抑制细菌易位，但具体机制不明。本研究运用SD大鼠SAP模型，采用HE染色病理分析、ELISA炎症介质检测、以及Western-Blot检测等，证实Omega-3PUFAs 能够抑制SAP时全身过度炎症反应，下调血浆TNF-α、IL-6、KC等炎症介质水平，降低肺组织MPO活性；Omega-3PUFAs 对SAP 引发的肠道黏膜屏障破坏具有抑制作用，其作用可能与促进Claudin-1蛋白表达相关。本研究运用单核细胞缺血缺氧(HI)模型，发现Omega-3PUFAs对HI时单核细胞释放促炎介质TNF-α、IL-6、IL-1具有下调抑制作用，对抗炎介质IL-10生成具有促进作用，其机制可能与抑制p38蛋白的磷酸化，从而抑制p38 MAPK信号通路相关。