为了研究木瓜提取物对非甾体抗炎药（NSAID）引起的小鼠小肠黏膜损伤的预防作用，应用灌胃方式连续6 d给与木瓜提取物，在第5 d给与双氯芬酸钠5 mg/mL连续两天灌胃，建立NSAID诱导小肠黏膜损伤模型。检测小肠黏膜通透性及观察小肠黏膜病变情况,检测葡萄糖转运蛋白（GRP-78）、CHOP、肿瘤坏死因子α（TNF-α）、Toll受体4（TLR4）及NLRP的表达水平。FITC-DT测定结果显示正常组相对荧光值（Relative fluorescence value，RFU）为682.7±105.4、模型组2008.3±496.1、木瓜低剂量组为1097.8±501.1、木瓜高剂量组为737.5±275.5；与正常组相比，模型组小鼠小肠黏膜明显损伤及通透性增加；与模型组相比，不同剂量木瓜提取物处理小鼠后能明显减轻小肠黏膜损伤，其机制与木瓜提取物调节肠道组织的内质网应激（GRP78和CHOP）、降低肠道炎症反应（TLR4和TNF-α）有关。提示木瓜提取物能通过调节TLR4-内质网应激预防NSAID对小鼠小肠黏膜的损伤。

The preventive effect of the extract of Chaenomeles speciosa (Sweet) Nakai (CS) on nonsteroidal anti-inflammatory drug (NSAID)-induced intestinal injuries in mice were investigated, mice were given the CS by intragastric administration for 6 days, and then the diclofenac sodium (5 mg/mL) was given to the stomach for 2 consecutive days on the 5th day to intestinal mucosal lesions were observed Expression levels of glucose transporter protein 78 (GRP-78), tumor necrosis factorα (TNF-α), Toll receptor 4 (TLR4), chop and NLRP were detected. The results of FITC-DT showed that the relative fluorescence value (RFU) of the normal group was 682.7±105.4, with 2008.3±496.1, 1097.8±501.1 and 737.5±275.5 for the model group , low CS dose group, and high CS dose group, respectively. Compared with the normal group, the extent of the small intestinal mucosal injury and permeability for the model group significantly increased. Compared with the model group, different CS doses could significantly reduce the small intestinal mucosal injury in mice, with the mechanism associated with the regulation of the endoplasmic reticulum stress (GRP78 and CHOP) and reduction of intestinal inflammation (TLR4 and TNF-α) by CS. These findings suggest that CS can prevent the damage of the small intestinal mucosa caused by NSAID in mice through regulating the TLR4-endoplasmic reticulum stress.

国家自然科学基金项目（81473461）