Song Wei-Bing, Lv Yong-Hui, Li Ya-Nan, Xiao Li-Ping, Yu Xin-Pei, Liu Gang, Wang Yuan-Yuan, Zhang Xiao-Lan, Li Ying-Fei
Department of Gerontology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Jul;29(7):1431-4.
To detect the changes in intestinal mucosal permeation in rats with methotrexate-induced small intestinal damage and investigate the protective effects of Changyanqing decoction.
Rat enteritis model was established by methotrexate (MTX) and sodium chloride. The rats were randomly divided into normal control group, model group, N-acetylcysteine (NAC) group and Changyanqing decoction group, and Changyanqing decoction (100 mg/kg) or saline was administered daily in the corresponding groups by gastric irrigation for 6 days. The disease activity index (DAI), colonic mucosal damage index (CMDI) and histological score (HS) of the rats were observed and evaluated. The levels of mRNA expressions of TNF-alpha and IL-1beta were detected by semi-quantitative RT-PCR. The expression of IL-10 was detected by enzyme linked immunosorbent assay, and IkappaB expression was determined with Western blotting.
Compared with the normal control group, the model group showed significantly increased DAI, CMDI and HS. The DAI, CMDI, and HS in rats treated with Changyanqing decoction were significantly decreased in comparison with those in the model group (P<0.01). The expressions of TNF-alpha and IL-1beta were significantly higher in MTX-treated group than in the control group. The expression of TNF-alpha and IL-1beta mRNA in the Changyanqing group and NAC group were significantly lower, but IL-10 significantly higher than those of the MTX group. In MTX group, obvious NF-kappaB activation was observed, whose expression was significantly stronger in the cell nuclei, and the IkappaB in the cytoplasm was markedly degraded.
Changyanqing decoction offers protection on intestinal mucosa by inhibiting NF-kappaB activation to reduce TNF-alpha and IL-1beta mRNA expressions and increase IL-10 expression.
检测甲氨蝶呤致大鼠小肠损伤时肠黏膜通透性的变化,并探讨肠炎清煎剂的保护作用。
采用甲氨蝶呤(MTX)和氯化钠建立大鼠肠炎模型。将大鼠随机分为正常对照组、模型组、N-乙酰半胱氨酸(NAC)组和肠炎清煎剂组,相应组每日经胃灌胃给予肠炎清煎剂(100mg/kg)或生理盐水,连续6天。观察并评估大鼠的疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)和组织学评分(HS)。采用半定量RT-PCR检测肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的mRNA表达水平。采用酶联免疫吸附测定法检测IL-10的表达,并用蛋白质印迹法测定IκB的表达。
与正常对照组相比,模型组的DAI、CMDI和HS显著升高。与模型组相比,肠炎清煎剂治疗的大鼠的DAI、CMDI和HS显著降低(P<0.01)。MTX治疗组中TNF-α和IL-1β的表达明显高于对照组。肠炎清组和NAC组中TNF-α和IL-1β mRNA的表达明显低于MTX组,但IL-10明显高于MTX组。在MTX组中,观察到明显的核因子-κB(NF-κB)激活,其在细胞核中的表达明显更强,细胞质中的IκB明显降解。
肠炎清煎剂通过抑制NF-κB激活,减少TNF-α和IL-1β mRNA表达,增加IL-10表达,对肠黏膜起到保护作用。