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目的:研究雷公藤多苷对2,4,6-三硝基苯磺酸(TNBS)/乙醇溃疡性结肠炎大鼠脂质过氧化损伤的保护作用。方法:通过TNBS联合乙醇灌肠的方法,建立TNBS/乙醇溃疡性结肠炎大鼠模型。造模成功后,90只雄性Wistar大鼠随机分为6组,每组15只,分别为正常对照组、模型对照组、雷公藤多苷3mg/kg、6mg/kg、12mg/kg、硫唑嘌呤6mg/kg,每组各自给予相应药物灌胃治疗,连续14天。每3天进行一次大鼠疾病活动指数(DAI)评分,所有大鼠在14天后均被解剖,相应结肠组织被留取,对各组大鼠结肠组织进行大体及镜下病理评分;同时,进行心脏取血,离心后取上清液,用ELISA法检测血清中MDA、SOD、GSH-Px、IL-1β和TNF-α含量。结果:DAI评分,大体及镜下表现和评分均提示TNBS/乙醇大鼠模型是研究溃疡性结肠炎的极佳模型,雷公藤多苷可显著改善溃疡性结肠炎大鼠临床症状及促进高质量的黏膜愈合,即镜下黏膜愈合,该作用与硫唑嘌呤6mg/kg相当或强于硫唑嘌呤6mg/kg。脂质过氧化反应相关因子ELISA结果提示:与正常对照组相比,模型对照组大鼠体内MDA水平显著升高,SOD、GSH-Px水平显著降低。与模型组相比,雷公藤多苷呈现剂量依赖性地抑制大鼠血清中MDA水平,增加大鼠血清中SOD、GSH-Px水平,其中雷公藤多苷12mg/kg组能显著抑制MDA、促进SOD、GSH-Px释放。同时,硫唑嘌呤6mg/kg的作用略好于雷公藤多苷12mg/kg,但无统计学差异。炎症因子ELISA结果提示雷公藤多苷呈剂量依赖性地抑制血清中IL-1β及TNF-α的表达,其中雷公藤多苷6mg/kg、12mg/kg、硫唑嘌呤6mg/kg与模型对照组相较抑制炎症因子释放更显著;雷公藤多苷12mg/kg与硫唑嘌呤6mg/kg对炎症因子IL-1β及TNF-α的抑制作用相当,但差异无统计学意义。结论:雷公藤多苷可显著减少TNBS/乙醇溃疡性结肠炎大鼠结肠黏膜镜下炎性细胞浸润,最终达到镜下黏膜愈合的目的,其机制之一是通过减少自由基生成、抑制脂质过氧化反应和增强抗氧化能力,抑制炎症因子释放,重新建立氧化还原平衡,抑制结肠炎症。
Objective: To study the protective effect of Tripterygium glycosides on lipid peroxidation in 2,4,6-trinitrobenzene sulfonic acid (TNBS) / ethanol ulcerative colitis rats. Methods: The TNBS / ethanol ulcerative colitis rat model was established by TNBS combined with ethanol enema. After successful model establishment, 90 male Wistar rats were randomly divided into 6 groups of 15 rats, which were normal control group, model control group, tripterygium glycosides 3mg / kg, 6mg / kg, 12mg / kg, Purine 6mg / kg, each group were given the corresponding drug gavage treatment for 14 days. The disease activity index (DAI) scores of rats were carried out every 3 days. All rats were dissected after 14 days. The corresponding colon tissues were taken for the gross and microscopic pathological score of the colon tissues in each group. At the same time, The heart was taken out of the blood, and the supernatant was taken after centrifugation. The contents of MDA, SOD, GSH-Px, IL-1β and TNF-α in serum were detected by ELISA. Results: The DAI score, gross and microscopic findings and scores all suggested that the TNBS / ethanol rat model was an excellent model for studying ulcerative colitis. Tripterygium glycosides significantly improved the clinical symptoms and promote high quality of ulcerative colitis rats Mucosal healing, that is, mucosal healing, the role of azathioprine 6mg / kg or stronger than azathioprine 6mg / kg. ELISA results of lipid peroxidation-related factors suggested that compared with the normal control group, the model rats in the control group MDA levels were significantly increased, SOD, GSH-Px levels were significantly lower. Compared with the model group, Tripterygium glycosides showed a dose-dependent inhibition of MDA in serum and increased levels of SOD, GSH-Px in serum. Tripterygium glycosides 12 mg / kg significantly inhibited MDA and promoted SOD, GSH-Px release. At the same time, the effect of azathioprine 6mg / kg slightly better than Tripterygium glycosides 12mg / kg, but no significant difference. ELISA results of inflammatory cytokines suggested that Tripterygium glycosides inhibited the expression of IL-1β and TNF-α in serum in a dose-dependent manner. Tripterygium glycosides 6mg / kg, 12mg / kg and azathioprine 6mg / kg were significantly different from the model control group Compared with the inhibition of inflammatory cytokines release more significant; Tripterygium glycosides 12mg / kg and azathioprine 6mg / kg on the inflammatory cytokines IL-1β and TNF-α inhibition was similar, but the difference was not statistically significant. CONCLUSION: Tripterygium glycosides can significantly reduce inflammatory cell infiltration in colonic mucosa of TNBS / ethanol ulcerative colitis rats and finally achieve the objective of microscopic mucosal healing. One of the mechanisms is that by reducing free radical production and inhibiting lipid Peroxidation and enhance the antioxidant capacity, inhibit the release of inflammatory cytokines, re-establish the redox balance, inhibit colitis.