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目的探讨雌激素影响大鼠炎症性肠病(inflammatory bowel disease,IBD)的具体机制。方法通过30%的2,4,6-三硝基苯磺酸(TNBS)乙醇溶液诱导建立大鼠IBD模型,通过测定体质量、疾病活动指数(disease activity index,DAI)评分、结直肠长度、髓过氧化物酶(MPO)浓度、H-E染色指标,以确定IBD建模成功。致炎后的IBD鼠,分别应用生理盐水(500μL)、雌激素(1mg/kg,溶于500μL生理盐水)、雌激素受体α(ERα)特异性激动剂PPT(3mg/kg,溶于500μL生理盐水)、雌激素(1mg/kg,溶于500μL生理盐水)+ERα特异性拮抗剂MPP(1mg/kg,溶于500μL生理盐水)作处理,观察大鼠炎症变化。结果 TNBS诱导大鼠IBD模型成功建立,大鼠体质量降低、DAI评分增大、MPO值增加、肠道炎症明显。与生理盐水处理组比较,用雌激素或PPT处理后加重了IBD大鼠炎症:雌激素干预后IBD大鼠体质量降低、DAI评分增大、结直肠长度缩短、肠道炎症加重;PPT干预后IBD大鼠体质量降低、DAI评分增大、结直肠长度缩短、肠道炎症加重。而MPP逆转了雌激素的促炎效应:与单独注射雌激素组比较,MPP干预后大鼠体质量增加、DAI评分降低、结直肠长度增加。结论雌激素促进TNBS诱导的IBD的发生发展,并且这种作用可能是通过ERα来完成的。
Objective To investigate the mechanism of estrogen on inflammatory bowel disease (IBD) in rats. Methods The rat model of IBD induced by 30% 2,4,6-trinitrobenzene sulfonic acid (ethanol) was established. The body mass, disease activity index (DAI) score, colorectal length, Myeloperoxidase (MPO) concentration, HE staining indicators to determine IBD modeling success. Inflammatory IBD rats were treated with normal saline (500μL), estrogen (1mg / kg dissolved in 500μL normal saline) and estrogen receptor α (ERα) specific agonist PPT (3mg / kg dissolved in 500μL (1mg / kg, dissolved in 500μL of normal saline) + ERα-specific antagonist MPP (1mg / kg, dissolved in 500μL of normal saline) for observation of inflammatory changes in rats. Results The rat model of IBD induced by TNBS was successfully established. The body weight of rats reduced, DAI score increased, MPO value increased, intestinal inflammation was obvious. Compared with the saline control group, the inflammation of IBD rats was increased after treatment with estrogen or PPT: the body mass of IBD rats decreased, the DAI score increased, the length of colorectal length shortened and the intestinal inflammation increased after estrogen intervention. After PPT intervention IBD rats reduced body weight, DAI score increased, shorten the length of the colorectal, intestinal inflammation increased. However, MPP reversed the proinflammatory effect of estrogen. Compared with estrogen injection alone, MPP increased body weight, decreased DAI score, and increased colorectal length. Conclusion Estrogen can promote the development of IBBS induced by TNBS, and this effect may be accomplished by ERα.