小檗碱对非甾体消炎药相关性肠损伤的保护作用及其机制研究

背景：近年非甾体消炎药（NSAIDs）相关性肠损伤的发生率明显升高，但目前尚缺乏有效防治NSAIDs相关性肠损伤的药物。目的：研究中药小檗碱对NSAIDs相关性肠损伤的治疗作用及其机制。方法：将40只大鼠随机分为对照组、模型组以及低、中、高剂量小檗碱干预组（分别为25、50、75mg·kg-1·d-1）。采用7.5mg·kg-1·d-1双氯芬酸制备NSAIDs相关性肠损伤模型。造模第5d处死所有大鼠，行小肠黏膜大体、组织学评分。以ELISA法检测小肠黏膜前列腺素（PG）E2含量，硝酸还原酶法检测小肠黏膜和血清NO含量，免疫组化法检测小肠黏膜环氧合酶（COX）-1、COX-2表达。结果：与对照组相比，模型组大鼠小肠大体评分和组织学评分明显升高（P〈0．05），小肠黏膜PGE，含量明显降低（P〈0．05），小肠黏膜和血清NO含量明显升高（P〈0．05），小肠黏膜COX-1表达明显降低（P〈0．05），COX-2表达明显升高（P〈0．05）。给予低、中、高剂量小檗碱干预后，上述指标明显改善（P〈0．05）。结论：小檗碱对NSAIDs相关性肠损伤具有保护作用，其机制可能与小檗碱致小肠黏膜PGE：、COX-1表达升高以及组织和血清NO含量、COX-2表达降低有关。

Protective Effect and Mechanism of Berberine on Intestinal Damage Induced by Non-steroidal Anti-inflammatory Drugs

Background： The incidence of non-steroidal anti-inflammatory drugs （NSAIDs）-related intestinal damage is increas- ing in recent years, however, there is still no effective drug for its prevention and treatment. Aims： To study the protective effect and mechanism of berberine on intestinal damage induced by NSAIDs. Methods： Forty rats were randomly divided into control group, model group, low dose berberine （25 mg · kg-1 · d-1 ） , moderate dose berberine （50 mg · kg-1 d-1 ） and high dose berberine （ 75mg·kg-1·d-1 ） intervention groups. Diclofenac 75mg·kg-1·d-1 was used to induce NSAIDs-related intestinal damage model. On the 5th day of establishment of NSAIDs-related intestinal damage, all the rats were sacrificed. Macroscopic score and histological score were assessed. Small intestinal mucosal prostaglandin E2 （ PGE2 ） concentration was determined by ELISA. Small intestinal mucosal and serum NO concentrations were detected by nitrate re- ductase method. Small intestinal mueosal cyclooxygenase （COX）-1 and COX-2 expressions were measured by immunohis- tocbemistry. Results：Compared with control group, macroscopic score and histological score in model group were signifi- cantly increased （ P 〈 0.05 ）, small intestinal mucosal PGE2 concentration was significantly decreased （ P 〈 0.05 ）, small intestinal mucosal and serum NO concentrations were significantly increased （P 〈 0.05 ） , small intestinal mucosal COX-1 expression was significantly decreased while COX-2 expression was significantly increased （ P 〈 0.05 ）. After intervention with different doses of berberine, all the above-mentioned indices were significantly improved （ P 〈 0.05 ）. Conclusions ： Berberine can exert protective effect on intestinal damage induced by NSAIDs and its mechanism may be related to the in- crease of PGE2 and COX-1, as well as decrease of NO and COX-2.