愈肠栓对溃疡性结肠炎大鼠PPARγ/NF-κB信号通路的影响  

Effect of Yuchang suppository on PPARγ/NF-κB signaling pathway in rats with ulcerative colitis

作　　者：郑丽红[1] 王海强[2] 丁晓明[1] 王馨[1] 范大伟 王楠楠[1] 魏明慧[1] 黄秋思 ZHENG Li-hong;WANG Hai-qiang;DING Xiao-ming;WANG Xin;FAN Da-wei;WANG Nan-nan;WEI Ming-hui;HUANG Qiu-si(The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150001, China;The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China;Mudanjiang First People’s Hospital, Mudanjiang 157000, China)

机构地区：[1]黑龙江中医药大学附属第二医院,黑龙江哈尔滨150001 [2]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040 [3]牡丹江市第一人民医院,黑龙江牡丹江157000

出　　处：《海南医学院学报》2019年第7期486-490,共5页Journal of Hainan Medical University

基　　金：黑龙江省自然科学基金(H2017061);黑龙江中医药大学校基金(201301);黑龙江省卫生计生委科研基金(2018235)~~

摘　　要：目的:探讨愈肠栓对实验性溃疡性结肠炎大鼠的治疗作用及PPARγ/NF-κB信号通路的影响。方法:采用2.4.6-三硝基苯磺酸(TNBS)/乙醇法复制UC大鼠模型,随机分为正常对照组、模型组、愈肠栓高剂量组、愈肠栓中剂量组、愈肠栓低剂量组和柳氮磺吡啶栓组,每组8只。治疗14 d后,观察大鼠一般状况并进行疾病活动指数评分,ELISA法检测大鼠血清TNF-α、IL-1β、IL-6含量变化;取结肠标本观察结肠黏膜损伤指数(CMDI)评分及结肠病理组织学变化;RT-PCR、Western blot法检测结肠组织中PPARγ、NF-κB基因及蛋白表达。结果:与正常对照组比较,模型组大鼠DAI、CMDI评分以及血清TNF-α、IL-1β、IL-6含量、结肠组织NF-κB p65 mRNA和蛋白表达水平显著增加(P<0.01),PPAR-γmRNA和蛋白表达水平显著减少(P<0.01)。而SASP栓组及愈肠栓各剂量组IL-1β、IL-6、TNF-α的含量及结肠组织NF-κB p65 mRNA和蛋白的表达水平均低于模型组,PPARγmRNA和蛋白的表达水平高于模型组(P<0.01～0.05)。在对大鼠结肠黏膜组织NF-κB p65、PPAR-γ基因和蛋白表达的改善方面,愈肠栓高剂量组和中剂量组明显优于低剂量组(P<0.01～0.05)。结论:愈肠栓对UC模型大鼠症状及病理组织学有明显的改善作用,其机制可能是通过激活PPARγ,阻断NF-κB信号通路活化,下调TNF-α、IL-1β等炎症因子的表达,使炎症反应减轻或消除,从而达到治疗UC作用。To investigate the therapeutic effect of Yuchang suppository on experimental ulcerative colitis rats and the effect of PPARγ/NF-κB signaling pathway. Methods: The UC rat model was replicated by 2.4.6-trinitrobenzenesulfonic acid (TNBS)/ethanol method and randomly divided into normal control group, model group, high-dose group of Yuchang suppository, middle dose group, Low-dose group and sulfasalazine group, 8 rats in each group. After 14 days of treatment, the general condition of the rats was observed and the disease activity index was scored. The changes of serum TNF-α, IL-1β and IL-6 levels were detected by ELISA. The colonic mucosal injury index (CMDI) score and colon were observed by colon specimens. Histopathological changes;RT-PCR and Western blot were used to detect the expression of PPARγ and NF-κB genes and proteins in colon tissue. Results: Compared with the normal control group, the DAI and CMDI scores in the model group and the levels of serum TNF-α, IL-1β, IL-6, NF-κB p65 mRNA and protein in colon tissue were significantly increased ( P < 0.01), PPAR -γ mRNA and protein expression levels were significantly reduced ( P <0.01). The levels of IL-1β, IL-6, TNF-α and the expression of NF-κB p65 mRNA and protein in colon tissue were lower than those in the model group, and the expression levels of PPARγ mRNA and protein were high. In the model group ( P <0.05 or P <0.01). In the improvement of NF-κBp65 and PPAR-γ gene and protein expression in rat colonic mucosa, the high-dose group and the middle-dose group were significantly better than the low-dose group ( P <0.01 or P <0.05). Conclusion: Yuchang suppository can significantly improve the symptoms and histopathology of UC model rats. The mechanism may be through activation of PPARγ, blocking the activation of NF-κB signaling pathway, and down-regulating inflammatory factors such as TNF-α and IL-1β. The expression is such that the inflammatory response is alleviated or eliminated, thereby achieving the therapeutic effect of UC.

关 键 词：愈肠栓 溃疡性结肠炎 PPARΓ NF-ΚB 

分 类 号：R285.5[医药卫生—中药学]