摘要
目的:观察雷公藤对坏死性小肠结肠炎(necrotizing enterocolitis,NEC)新生大鼠的影响,并探讨其通过调控葡萄糖调节蛋白78(GRP78)—激活转录因子6(ATF6)—增强子结合蛋白同源蛋白(CHOP)通路发挥作用的。方法:采用缺氧+冷刺激法建立新生大鼠NEC模型,分为模型组、雷公藤多苷低剂量组(9 mg·kg^(-1))、雷公藤多苷中剂量组(18 mg·kg^(-1))、雷公藤多苷高剂量组(27 mg·kg^(-1)),另设对照组。检测粪便肠道菌群变化,肠组织病理学改变,肠组织中白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平及GRP78、ATF6、CHOP蛋白表达。结果:与模型组比较,雷公藤多苷低、中、高剂量组肠组织损伤评分、肠球菌总数、革兰氏阳性(G+)球菌比率、肠组织IL-1β和TNF-α水平及GRP78、ATF6、CHOP蛋白表达均明显降低(P<0.05),肠杆菌总数、杆/球菌比值、G+杆菌比率、肠组织IL-6水平均明显升高(P<0.05)。其中肠组织损伤评分、肠球菌总数、G+球菌比率、肠组织IL-1β和TNF-α水平及GRP78、ATF6、CHOP蛋白表达,雷公藤多苷低剂量组>中剂量组>高剂量组;肠杆菌总数、杆/球菌比值、G+杆菌比率、肠组织IL-6水平,雷公藤多苷低剂量组<中剂量组<高剂量组。结论:雷公藤多苷可改善NEC新生大鼠的肠道菌群紊乱现象,且可能通过抑制GRP78-ATF6-CHOP通路发挥肠道保护作用。
Objective:To observe the effect of tripterygium glycosides on the distribution of intestinal flora in neonatal rats with necrotizing enterocolitis(NEC),and to explore its regulatory mechanism through the glucose regulated protein 78(GRP78)-activating transcription factor 6(ATF6)-enhancer binding protein homologus protein(CHOP)pathway.Methods:The neonatal rat NEC model was established by hypoxia+cold stimulation,which was divided into model group,tripterygium glycoside low-dose group(9 mg·kg^(-1)),tripterygium glycoside medium-dose group(18 mg·kg^(-1)),tripterygium glycoside high-dose group(27 mg·kg^(-1)),and control group.Detection of changes in fecal intestinal flora,intestinal histopathological changes,interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor(TNF-α)level and GRP78,ATF6,CHOP protein expression in intestinal tissue.Results:Compared with the model group,the scores of intestinal tissue damage,the total number of enterococci,the ratio of gram-positive(G+)cocci,the levels of IL-1β,TNF-α,and the relative protein expression of GRP78,ATF6,and CHOP in the intestinal tissue in the low,medium,and high dose groups of tripterygium glycoside were obviously decreased(P<0.05).The total number of enterobacteria,rod/coccus ratio,G+bacillus ratio,and the level of IL-6 in the intestinal tissue are increased(P<0.05).Among them,intestinal tissue injury score,total number of enterococci,G+cocci ratio,the level of IL-1β,TNF-αGRP78,ATF6,CHOP protein expression in the intestinal tissue and,tripterygium glycoside low-dose group>medium-dose group>high-dose group;The total number of enterobacter the ratio of rod/coccus,the ratio of G+bacilli,the level of IL-6 in the intestinal tissue,tripterygium glycoside low-dose group<medium-dose group<high-dose group.Conclusion:Tripterygium glycoside polyglycosides can improve the intestinal flora disorder of NEC neonatal rats,and its regulatory mechanism may be related to the inhibition of GRP78-ATF6-CHOP pathway.
作者
高鹏
周凤蕊
刘俊华
周川
GAO Peng;ZHAO Fengrui;LIU Junhua;ZHOU Chuan(The Sixth People's Hospital of Zhengzhou,Zhengzhou Henan China 450015;The Second Affliated Hospital of Zhengzhou University,Zhengzhou Henan China 450000)
出处
《中医学报》
CAS
2021年第4期801-806,共6页
Acta Chinese Medicine
基金
河南省医学科技攻关计划项目(2018020154)。
