雌激素通过雌激素受体α加重大鼠炎症性肠病

Estrogen aggravates inflammatory bowel disease in rats through estrogen receptor alpha

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 explore the specific mechanism by which estrogen affects the inflammatory bowel disease （IBD） in rats. Methods The model of IBD in rats was established with 30% of 2, 4, 6-trinitrobenzene sulfonic acid （TNBS） ethanol solution through the rectocolon. The body weight, disease activity index（DAD score, eolorectal length, myeloperoxidase （MPO） concentration, and H-E staining were used to verify the successful IBD model. The IBD rats were separately treated with saline（500μL）, estrogen（1 mg/kg, in 500 μL normal saline）, and PPT, a specific agonist of estrogen receptor alpha （ERα; 3 mg/kg, in 500 μL normal saline）, or estrogen（1 mg/kg,in 500 μL normal saline） ＋ ERα specific antagonist MPP（3 mg/kg, in 500 μL normal saline）. And the inflammation status was observed. Results The model of IBD in rats was successfully induced by TNBS. Compared with the normal saline group, rats in TNBS group had significantly reduced body weight and increased DAI scores, with MPO value increased and with notable inflammatory response of the rectocolon. Compared with normal saline group, estrogen or PPT significantly aggravated the inflammation response. Estrogen treatment significantly reduced the body weight of IBD rats, increased DAI scores, and aggravated the inflammatory response, with the colorectal length reduced; PPT reduced the colorectal length. MPP treatment reversed the effect of estrogen. Compared with the estrogen group, MPP＋ estrogen treatment significantly increased the body weight and reduced the DAI scores, with colorectal length increased. Conclusion Estrogen can promote the development and progression of TNBS-induced IBD, which might be mediated through ERα.