姜黄素对DON暴露猪小肠上皮细胞紧密连接的保护作用及p38信号机制

DDeoxynivalenol (DON) is a mycotoxin that contaminates food and feedstuffs widely and is difficult to remove. The damage of deoxynivalenol to pigs is the most serious, hindering the healthy development of pig industry. The small intestine is the primary target of DON, which injury the intestinal epithelial cells tight junction (TJ) by activating p38 signal, leading to intestinal mucosal barrier dysfunction. Curcumin can protect intestinal epithelial cells TJ, and our previous research found that curcumin protects IPEC-J2 cell against DON-induced toxicity. Thus, we propose a theoretical hypothesis that curcumin intervenes DON-induced intestinal epithelial cells TJ injury and regulated by p38 signal. IPEC-J2 cell was used as research object, and the cells will be exposed to curcumin and DON for barrier function, as well relevant indicators of TJ and p38 signal, to determine the effects of curcumin on intestinal epithelial cells TJ and p38 signal. And then the cells were intervened with p38 agonist for screening out the action target of curcumin. Afterwards, we take Bama minipig as research object, and observe barrier function, relevant indicators of TJ and p38 signal, as well the content of DON in blood and dejecta, to verify the protective effects of curcumin on TJ and p38 signal in DON-exposed small intestinal epithelium. The results can provide theoretical basis for relieving DON intestinal toxicity.

脱氧雪腐镰刀菌烯醇（DON）是一种在食品和饲料中污染广泛且难以去除的霉菌毒素，对猪的危害最严重。小肠是DON首要攻击的靶组织，其通过激活p38信号损伤小肠上皮细胞紧密连接（TJ），破坏小肠上皮屏障功能。姜黄素具有保护肠上皮TJ的药理作用，且申请者前期研究证实姜黄素可保护猪IPEC-J2小肠上皮细胞免受DON毒性损伤，故提出姜黄素干预DON致猪小肠上皮TJ损伤并受p38信号调节的理论假说，先以IPEC-J2细胞为受试对象，通过对细胞屏障功能、TJ和p38信号关键因子的检测，确定姜黄素对DON暴露小肠上皮细胞TJ和p38信号的影响；通过添加p38激动剂，明确其调节作用；再以猪为受试对象，通过检测小肠上皮屏障功能、TJ和p38信号关键因子及血液和粪便中DON含量，验证姜黄素对DON暴露猪小肠上皮TJ的保护效果及p38信号机制，筛选出姜黄素的作用靶点。研究结果可为DON肠毒性的解除提供理论依据。

脱氧雪腐镰刀菌烯醇（DON）是一种在食品和饲料中污染广泛且难以去除的霉菌毒素，对猪的危害最严重。小肠是DON首要攻击的靶组织，其通过激活p38信号损伤小肠上皮细胞紧密连接（TJ），破坏小肠上皮屏障功能。姜黄素具有保护肠上皮TJ的药理作用，故提出姜黄素干预DON致猪小肠上皮TJ损伤并受p38信号调节的理论假说，并以p38信号对TJ相关因子表达和分布的调节作用为研究切入点，以IPEC-J2细胞、p38激动剂干预的IPEC-J2细胞和小型猪为受试对象，建立姜黄素干预DON暴露体外细胞试验模型和在体试验模型，通过观测IPEC-J2细胞和小肠组织的屏障功能、TJ和p38信号关键因子的变化，获得了如下开创性结果：（1）姜黄素可缓解DON导致的IPEC-J2细胞和小肠组织结构损伤和屏障功能障碍；（2）姜黄素可通过抑制p38信号调节TJ关键因子的表达和分布，进而缓解DON导致的小肠上皮细胞TJ损伤；（3）初步筛选出p38为姜黄素保护DON暴露小肠上皮TJ的作用靶点，进一步确认了p38为DON肠毒性损伤的防治靶点。研究结果可为DON致猪肠毒性的解除和姜黄素维护肠道健康提供理论依据和实验基础。