摘要
目的：观察新麦纤散对溃疡性结肠炎（ulcerative colitis,UC）大鼠蛋白激酶R样内质网激酶（PERK）/真核翻译起始因子-2α（eIF-2α）/核转录因子-κB（NF-κB）信号通路的调控作用,探究其对UC的疗效和作用机制。方法：将60只SD大鼠随机分成正常组、模型组、美沙拉嗪组、新麦纤散低、中、高剂量组,每组10只,采用葡聚糖硫酸钠（dextran sulfate sodium,DSS）成功诱导UC模型后,美沙拉嗪组给予美沙拉嗪缓释颗粒混悬液0.42 g·kg^（-1）·d^（-1）,新麦纤散低、中、高剂量组分别给予新麦纤散混悬液1.5,3,6 g·kg^（-1）·d^（-1）,其余组给予等体积生理盐水,连续灌胃14 d。评估UC大鼠疾病活动指数（DAI）,酶联免疫吸附法（ELISA）检测血清NF-κB表达水平,蛋白免疫印迹法（Western blot）和实时荧光定量聚合酶链式反应法（Real-time PCR）分别观察结肠组织PERK,eIF-2α蛋白和mRNA的表达。结果：与正常组比较,模型组DAI评分和血清NF-κB水平显著升高（P〈0.05）,结肠组织PERK,eIF-2α蛋白和mRNA水平均升高（P〈0.05）;与模型组比较,新麦纤散组DAI评分减少,血清NF-κB水平降低（P〈0.05）,新麦纤散中、高剂量组PERK,eIF-2α蛋白和mRNA的表达均降低（P〈0.05）。结论：新麦纤散对UC大鼠有较好的疗效,其作用机制可能与抑制PERK/eIF-2α/NF-κB信号通路的激活有关。
Objective： To investigate the curative effect and the mechanism of Xinmaixian powder in ulcerative colitis（ UC） rats by observing its regulatory effect on protein kinase R like endoplasmic reticulum kinase（ PERK）/eukaryotic translation initiation factor-2α（ eIF-2α）/nuclear factor-κB（ NF-κB） signaling pathway.Method： Sixty SD rats were randomly divided into six groups： normal group,model group,mesalazine group,Xinmaixian powder low, middle and high dose groups,with 10 rats in each group. After UC models were successfully prepared by dextran sodium sulfate（ DSS）, the rats in mesalazine group received mesalazine sustained-release granules suspension in the dose of 0. 42 g·kg^（-1）·d^（-1） for 14 days; the rats in Xinmaixian powder low,middle and high dose groups were treated with Xinmaixian powder suspension in the dose of 1. 5,3,and 6 g·kg^（-1）·d^（-1） respectively for 14 days. The other groups were treated with same volume of normal saline for 14 days.Finally,the scores of disease activity index（ DAI） were evaluated; and expression levels of NF-κB in serum were tested by enzyme-linked immunosorbent assay（ ELISA）. In addition,protein expression levels of PERK and eIF-2α in colonic tissues were detected by Western blot,while mRNA expression levels of PERK and eIF-2α in colonic tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（ Real-time PCR）. Result：DA-I scores,expression levels of NF-κB in serum and the protein and mRNA expression levels of PERK and eIF-2α in colonic tissues in the model group were significantly higher than those in normal group（ P 0. 05）. As compared with the model group,Xinmaixian powder groups can reduce DAI scores and expression levels of NF-κB in serum（ P 0. 05）,and the protein and mRNA expression levels of PERK and eIF-2α were also decreased in Xinmaixian powder middle and high dose groups（ P 0. 05）. Conclusion： Xinmaixian powder has a good curative effect on UC rats,and its therapeutic mechanism may be related to inhibiting the activation of PERK/eIF-2α/NF-κB signaling pathway.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第5期126-130,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
浙江省科技计划项目(2016C33085)
