熊果酸对酒精诱导的大鼠小肠黏膜屏障损伤的保护作用
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国家自然科学基金项目(81760586); 内蒙古自治区自然科学基金项目(2019LH08039); 内蒙古自治区卫生计生科研计划项目(201701084)


Protective Effect of Ursolic Acid on Intestinal Mucosal Barrier Injury in Alcohol-induced Rats
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    摘要:

    目的:研究熊果酸(UA)对酒精诱导的大鼠小肠黏膜屏障损伤的保护作用。方法:将SD大鼠随机分为正常对照组,每日给予生理盐水灌胃;酒精模型组,每日给予体积分数50%酒精8 mL/(kg bw·d)灌胃2周,第3周开始以12 mL/(kg bw·d)灌胃;熊果酸组,每日给予150 mg/(kg bw·d)熊果酸,1 h后再灌酒精,剂量同酒精模型组;谷氨酰胺组,每日给予300 mg/(kg bw·d)谷氨酰胺,酒精灌胃同熊果酸组,试验持续8周。采用HE染色法观察大鼠小肠黏膜组织病理学变化;利用透射电镜观察小肠黏膜细胞超微结构的改变;检测了大鼠血浆D-乳酸(D-LA)、肠脂肪酸结合蛋白(FABP2)、肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)质量浓度的改变;测定了小肠组织中叉头框转录因子O4(FOXO4)、磷酸化叉头框转录因子O4(p-FOXO4)、和闭锁小带蛋白-1(ZO-1)的表达水平。结果:酒精模型组小肠绒毛萎缩、变短,排列不整,紧密连接肿胀,有炎性细胞浸润。与酒精模型组相比,熊果酸组和谷氨酰胺组大鼠小肠黏膜病理变化有所改善;血浆D-LA、FABP2、TNF-α和IL-1β质量浓度明显降低;p-FOXO4表达量减少、ZO-1表达量升高;各组FOXO4表达水平无显著差异。结论:熊果酸可以改善酒精诱导的大鼠小肠黏膜屏障损伤,其作用机制可能与改善肠黏膜通透性,抑制FOXO4蛋白发生磷酸化,进而减少促炎因子TNF-α和IL-1β的释放有关。

    Abstract:

    Objective: To explore the protective effect of ursolic acid (UA) on intestinal mucosal barrier injury in alcohol-induced rats. Methods: SD rats were randomly divided into 4 group. Rats of normal control group received physiological saline by gavage for every day. Rats of alcohol model group were given oral dose of 8 mL/(kg bw·d) of 50% alcohol for the first to the second week, a dose of 12 mL/(kg bw·d) from the third week. Ursolic acid group were administered orally with 150 mg/(kg bw·d) UA for every day and received alcohol by gavage 1 hour later. Glutamine group were given 300 mg/(kg bw·d) glutamine by gavage for every day and the alcohol dose was the same as that of ursolic acid group. After 8 weeks, morphological examination of intestinal tissue was performed by hematoxylin and eosin (H&E) staining, and the ultrastructure of intestinal mucosal was observed by transmission electron microscopy. The levels of D-lactic acid (D-LA), intestinal fatty acid binding protein (FABP2), tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in plasma were detected. The expressions of forkhead box O4 (FOXO4), p-FOXO4, and zonula occludens-1(ZO-1) in intestinal tissues were detected. Results: The morphological structure and the ultrastructure of intestinal tissues showed the villi of the rats in the alcohol model group were atrophic and short, the tight junction were swelling and the inflammatory cell infiltration was obvious. The pathological changes of small intestine mucosa in the ursolic acid group and glutamine group were better than alcohol model group. Plasma concentrations of D-LA, FABP2, TNF-α and IL-1β were significantly decreased. The expression of p-FOXO4 was decreased, ZO-1 was increased compared model group. There was no significant difference in FOXO4 expression. Conclusion: UA attenuates the damage of intestinal mucosal barrier injury caused by alcohol in rats, and its mechanism may be related to improving intestinal mucosal permeability, inhibiting the phosphorylation of FOXO4 protein, and thereby reducing the release of pro-inflammatory factors TNF-α and IL-1β.

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贾逸林;杨冬晗;李可欣;张文龙;王朝亮;戈娜;.熊果酸对酒精诱导的大鼠小肠黏膜屏障损伤的保护作用[J].中国食品学报,2021,21(8):128-135

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  • 在线发布日期: 2021-09-19
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