【摘要】 目的:观察养阴活胃合剂对CAG大鼠胃黏膜细胞TLRs及其信号转导通路的影响,揭示养阴活胃合剂治疗CAG的治疗途径与作用靶点,分别从分子水平、蛋白水平阐述养阴活胃合剂治疗CAG的作用机制,并通过测定炎症因子的变化情况观察养阴活胃合剂在抗炎方面的作用。方法:将实验动物随机分为6组:空白对照组、模型组、阳性药物对照组及中药低剂量组、中剂量组、高剂量组,每组16只。除空白对照组常规饲养、自由进食水之外,其余5组将2 g水杨酸钠加入100 m L的30%乙醇溶液中,给大鼠灌胃,1次/d,3 m L/次,配合隔日喂食不禁水法建立大鼠萎缩性胃炎模型,模型复制成功后中药治疗低、中、高剂量组分别喂饲养阴活胃合剂水煎剂0.74 g/kg·d、1.48 g/kg·d和2.22 g/kg·d。12周后测定血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、干扰素-β(IFN-β)诱导型一氧化氮合成酶(NOS2)四种炎症因子含量,测定TLRs及其下游转导元件m RNA及蛋白的含量。结果:养阴活胃合剂能够改善大鼠胃黏膜病理状态,使病变胃黏膜趋于正常。与空白对照组比较,各组炎症因子及TLRs及其下游信号转导元件蛋白及m RNA含量均明显升高(P<0.05),证明模型复制成功。与模型组相比,中药高剂量组TNF-α、IL-6、NOS2含量均明显降低,阳性药物对照组及各中药剂量组对TLRs及其下游信号转导元件蛋白及m RNA含量均有不同程度的降低,差异有统计学意义(P<0.05)。而各养阴活胃剂量组之间比较,中药中剂量组IFN-β降低,中药高剂量组TLRs及其下游信号转导元件蛋白及m RNA含量均有不同程度下降,差异有统计学意义(P<0.05)。结论:1)养阴活胃合剂可以通过调控TLR样受体及其下游转导元件基因及蛋白水平,降低因TLRs通路激活所释放的炎症因子对胃黏膜的损伤,从而达到治疗慢性萎缩性胃炎的目的。2)养阴活胃合剂可降低慢性萎缩性胃炎大鼠血清中炎症因子水平,而抑制炎性反应可能有助于慢性萎缩性胃炎病情的改善。更多还原

【Abstract】 Objective: To observe the effect of Yangyin Huowei mixture on gastric mucosal cells and TLRs signal transduction pathway of rats with Chronic Atrophic Gastritis( CAG). In addition,to reveal the mechanism of Yangyin Huowei mixture in the treatment of CAG from molecular level and protein level and its anti inflammation changes from inflammatory factors. Methods: To randomly divide the experimental rats into 6 groups: blank control group,model group,positive drug group,low dose of Chinese medicine group,medium dose group,and high dose group,with 16 rats in each group. Except for the blank control group,which was given conventional breeding and free access to food and water,the other groups were given 2 g sodium salicylate adding into 100 m L 30% ethanol solution,1 time a day,each time 3 m L. With feeding on alternate days without water,the establishment of CAG rats model were successfully reproduced. Yangyin Huowei mixture of water decoction of 0. 74 g / kg / d,1. 48 g / kg / d,and 2. 22 g /kg / d were given respectively to low dose of Chinese medicine group,medium dose group,and high dose group. After 12 weeks,to determine the level of serum IL-6,TNF-α,IFN-β and NOS2 inflammatory factor and measure the original TLRs and downstream transduction m RNA and protein content. Results: Yangyin Huowei mixture can improve CAG and gastric mucosa lesion. Compared with blank control group,inflammatory factor,TLRs and its downstream signal transduction proteins and m RNA content in each group were significantly increased( P < 0. 05),which proved that the models were reproduced successfully. Compared with model group,TNF-α,IL-6,NOS2 levels of high dose group were significantly lower,and in positive drug control group and the traditional Chinese medicine dose group,TLRs and its downstream signal transduction proteins and m RNA content also reduced,be-sides,the difference was statistically significant( P < 0. 05). In the comparison among Chinese medicine groups,IFN-β decreased in middle-dose group,and in high dose group,TLRs and its downstream signal transduction proteins and m RNA content declined,and the difference was statistically significant( P < 0. 05). Conclusion:( 1) Yangyin Huowei mixture can improve original sample TLR receptors and their downstream transduction genes and protein level,reduce the release of inflammatory factor by TLRs pathway activation,and thus to treat CAG.( 2) Yangyin Huowei mixture can reduce the serum level of inflammatory factors of CAG,and this may contribute to the improvement of CAG.更多还原