白芍总甙对大鼠实验性结肠炎Th17细胞相关因子的作用

Total glucosides of paeony mitigate trinitrobenzene sulfonic acid-induced experimental colitis in rats

目的:观察白芍总甙(TGP)对实验性结肠炎干预的治疗效果,探讨TGP对实验性结肠炎的抗炎作用.方法:40只SD大鼠以三硝基苯磺酸(TNBS)/乙醇溶液灌肠诱导结肠炎模型,均分为结肠炎模型组、正常对照组(0.9%NaCl溶液灌肠)、TGP组(100mg/kg)和5-ASA药物对照组(100mg/kg).连续灌胃14d后行结肠大体损伤指数(CMDI)和组织学损伤指数(TDI)评分,ELISA检测血清IL-6、IL-17及IL-23水平,免疫组织化学SP法检测结肠组织TGF-β1与Foxp3的表达.结果:与结肠炎模型组相比,正常组CMDI、TDI,血清IL-6,IL-17及IL-23含量明显低,结肠组织TGF-β1和Foxp3含量明显高.5-ASA与TGP能显著降低CMDI和TDI(2.78分±2.11分,3.56分±1.94分vs6.88分±0.84分,均P<0.05;2.22分±0.83分,2.44分±1.51分vs5.63分±0.74分,均P<0.05),降低血清IL-6,IL-17和IL-23含量(5-ASA:t=5.998,2.438,2.670,均P<0.05;TGP:t=5.203,3.013,2.962,均P<0.05),升高结肠组织中TGF-β1和Foxp3(5-ASA:t=6.026,3.022,均P<0.05;TGP:t=6.198,2.734,均P<0.05).TGP组与5-ASA组无明显统计学差异.结论:TGP可能通过上调TGF-β1和Foxp3水平,促进Treg细胞的表达,抑制Th17细胞群的活化,下调IL-6,IL-17和IL-23的表达,减轻TNBS诱导的大鼠实验性结肠炎的症状和结肠炎性损伤.

AIM： To investigate the effects of total glucosides of paeony （TGP） on experimental colitis in rats and explore potential mechanisms involved. METHODS： Colitis was induced in 40 rats by rectal administration of trinitrobenzene sulfonic acid （TNBS） dissolved in ethanol. The model rats were divided into three groups （n = 10）： model control group （undergoing no treatment）, TGP treatment group （treated with 100 mg/kg TGP）, and olsalazine treatment group （treated with 100 mg/kg olsalazine）. A normal control group wascomposed of 10 normal rats receiving 0.9% NaCl solution. After 2-week intervention, the colonic macroscopic damage index （CMDI） and tissue damage index （TDI） were evaluated, the serum levels of interleukin-6 （IL-6）, IL-17 and IL-23 were determined by enzyme-linked immunosorbant assay （ELISA）, and the colonic expression of transforming growth factor-β1 （TGF-β1） and forkhead box P3 （Foxp3） was determined by immunohistochemistry. RESULTS： Compared with the model control group, the CMDI and TDI decreased significantly （2.78 ± 2.11 and 3.56 ± 1.94 vs 6.88 ± 0.84, and 2.22 ± 0.83 and 2.44 ± 1.51 vs 5.63 ± 0.74, respectively; all P〈0.05）, the serum levels of IL-6, IL-17 and IL-23 also declined significantly （5-ASA： t = 5.998, 2.438 and 2.670, respectively, all P〈0.05; TGP： t = 5.203, 3.013 and 2.962, respectively, all P〈0.05）, and the colonic expression levels of TGF-β1 and Foxp3 increased significantly （5-ASA： t = 6.026 and 3.022, respectively, both P〈0.05; TGP： t = 6.198 and 2.734, respectively, both P〈0.05） in the TGP treatment group and the olsalazine treatment group. No significant differences were found in the above parameters between the TGP treatment group and the olsalazine treatment group. CONCLUSION： TGP can attenuate the symptoms and colonic inflammatory damage in TNBSinduced experimental colitis in rats possibly via a mechanism associated with inhibition of Th17 cell activation, downregulation of IL-6, IL-17 and IL-23, and upregulation of TGF-β1 and Foxp3.