冬凌草甲素对小鼠溃疡性结肠炎内质网应激的作用研究

Effects of oridonin on endoplasmic reticulum stress in ulcerative colitis mouse model

目的探讨冬凌草甲素对溃疡性结肠炎(UC)小鼠的结肠上皮组织内质网应激(ERS)的影响。方法利用葡聚糖硫酸钠(DSS)建立小鼠UC模型组,设置冬凌草甲素及柳氮磺胺吡啶干预组;测定疾病活动指数(DAI),对结肠组织进行病理形态学评分(HPS),RT-qPCR检测结肠上皮组织肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、环氧合酶-2(COX-2)、葡萄糖调节蛋白78(GRP78)、转录因子EBP同源蛋白(CHOP)、激活性转录因子6(ATF6)、蛋白激酶R样内质网激酶(PERK)及肌醇酶1α(IRE1α)mRNA表达变化。结果与健康小鼠相比,模型组结肠上皮组织中TNF-α、IL-6、COX-2、GRP78、ATF6、CHOP、PERK及IRE1αmRNA表达均明显上调(P<0.05,P<0.01);与模型组比较,冬凌草甲素干预组DAI与HPS均明显下降(P<0.05,P<0.01),疗效与柳氮磺胺吡啶干预组相当(P>0.05,P<0.01),除IER1αmRNA外,TNF-α、IL-6、COX-2、GRP78、CHOP、ATF6及PERK mRNA表达水平均明显下调(P<0.05,P<0.01)。结论冬凌草甲素能减轻DSS诱导小鼠结肠炎症,其机制可能与其调节结肠上皮组织ERS有关。

Objective To explore the effect of oridonin on the endoplasmic reticulum stress （ERS） in colonic epithelium of ulcerative colitis （UC） mice. Methods The UC mice model was established by sodium dextran sulfate （DSS）,and the intervention group of oridonin and sulfasalazine was set up,the disease activity index （DAI） was measured,the colonic tissue was evaluated by histopathologidscore （HPS）,and RT-qPCR was used to detect the expression of inflammatory cytokines tumor factor-α （TNF-α）,interleukin 6 （IL-6）,cyclooxygenase 2 （COX-2）,glucose-regulated protein 78 （GRP78）,transcription factor EBP homologous protein （CHOP）,activator transcription factor 6 （ATF6）,protein kinase R like endoplasmic reticulum kinase （PERK） and inositol requiring enzyme 1α （IRE1α）. Results The expression of TNF-α,IL-6,COX-2,GRP78,ATF6,CHOP,PERK and IRE1α mRNA in the colonic epithelium of the model group were all up-regulated obviously as compared with the healthy control group（ P 〈0.05, P 〈0.01）.When compared with the model group,DAI and HPS in oridonin-treated group were significantly decreased （ P 〈0.05, P 〈0.01）,which the curative effect was similar to that of the sulfasalazine group（ P 〉0.05, P 〈0.01）.The expression of TNF-α,IL-6,COX-2,GRP78,CHOP,ATF6 and PERK mRNA levels were significantly reduced in oridonin-treated group（ P 〈 0.05 , P 〈0.01）. Conclusion Oridonin can alleviate colonic inflammation induced by DSS and its mechanism may be related to ERS of colonic epithelial tissue.