姜黄素通过过氧化物酶体增生物激活受体-γ在大鼠实验性结肠炎中发挥抗炎作用

Antiinflammatory Effect of Curcumin on Experimental Colitis in Rats via Peroxisome Proliferator-activated Receptor-γ

背景:研究显示姜黄素可激活过氧化物酶体增生物激活受体(PPAR)-γ,抑制三硝基苯磺酸(TNBS)诱导的大鼠结肠炎症。目的:以姜黄素和PPAR-γ拮抗剂GW9662单独或联合干预结肠炎模型大鼠,探讨姜黄素在大鼠实验性结肠炎中的抗炎机制。方法:以直肠内注入TNBS/乙醇溶液制备大鼠结肠炎模型。模型大鼠分别腹腔注射二甲基亚砜(DMSO)、姜黄素、GW9662或GW9662+姜黄素2周,评价各组大鼠的死亡率、结肠损伤评分、血清促炎因子白细胞介素(IL)-2和抗炎因子IL-10水平以及结肠组织PPAR-γ和核因子(NF)-κB的表达。结果:与模型对照组相比,姜黄素能明显降低大鼠死亡率、结肠黏膜大体、组织学损伤评分和血清IL-2水平,升高血清IL-10水平,结肠组织PPAR-γ表达增高,NF-κB表达减低(P<0.05);GW9662+姜黄素组大鼠结肠炎症无明显改善。正常对照组、模型对照组和姜黄素组PPAR-γ与NF-κB的表达均呈负相关(P<0.01)。结论:姜黄素可通过PPAR-γ途径负性调节NF-κB的表达,在TNBS诱导的大鼠结肠炎中发挥抗炎作用。

Background：It has been reported that curcumin could inhibit trinitrobenzene sulphonic acid （TNBS）-induced colitis in rats by activating peroxisome proliferator-activated receptor （PPAR）-γ Aims： To investigate the antiinflammatory mechanism of curcumin in experimental colitis in rats by treating the colitis model in rats with curcumin, GW9662 （an antagonist of PPAR-γ and combination of these two agents. Methods： Colitis model in rats was established by instillation of TNBS/ethanol solution into rectum. After intraperitoneal injection of dimethyl sulfoxide （DMSO）, curcumin, GW9662 or GW9662＋curcumin, respectively for two weeks, the mortality rate, score of mucosal damage, serum levels of proinflammatory cytokine interleukin （IL）-2, antiinflammatory cytokine IL-10, colonic expression of PPAR-γnd nuclear factor （NF）-κB were determined and appraised. Results： As compared with the model control group, the mortality rate, macroscopic and histological score of colon mucosa, serum level of IL-2 and colonic expression of NF-κB in curcumin group were significantly decreased, and serum level of IL-10 and colonic expression of PPAR-γsignificantly increased （P〈0.05）; no significant improvement of colonic inflammation was observed in GW9662＋curcumin group. Expression of PPAR-γ was negatively correlated with expression of NF-κB in the normal control, model control and curcumin groups （P〈0.01）. Conclusions： Curcumin can exert antiinflammatory effect on colitis in rats induced by TNBS partially via PPAR-γactivation and subsequent down-regulation of NF-κB.