清肠化湿方对TNBS大鼠结肠组织PPAR-γ/p38 MAPK的影响  

Effects of Qingchang Huashi Decoction on Expression of PPAR-γ and p38 MAPK in Colonic Mucosa of Rats with Ulcerative Colitis

作　　者：顾培青[1] 沈洪[1] 朱磊[1] 刘亚军[1] 张露[1] 刘军楼[1] 徐艺[1] 成家飞[1] 

机构地区：[1]江苏省中医院,江苏南京210029

出　　处：《山东中医药大学学报》2017年第1期81-85,共5页Journal of Shandong University of Traditional Chinese Medicine

基　　金：国家自然科学基金委员会青年科学基金项目(编号:81302919);江苏省中医药局科技项目立项计划(编号:LZ13048);江苏省中医院高峰学术人才培养工程(编号:k2014yrc13);江苏省中医院院级课题(编号:Y14076)

摘　　要：目的 :观察清肠化湿方(QHD)对三硝基苯磺酸(TNBS)诱导的大鼠结肠炎结肠组织中过氧化物酶体增殖物激活受体(PPAR-γ)和p38丝裂原活化蛋白激酶(p38 MAPK)表达的影响,探讨其治疗溃疡性结肠炎(UC)的可能作用机制。方法:采用80只Wistar大鼠建立UC大鼠模型,随机分为8组,分别为空白对照组、模型对照组、QHD低剂量组、QHD中剂量组、QHD高剂量组、柳氮磺胺吡啶(SASP)组、柳氮磺胺吡啶+双酚A-二甘氨酸醚(SASP+BADGE)组及中药中剂量+BADGE组,每组10只。除空白对照组以生理盐水灌肠外,其余组采用TNBS/乙醇灌肠造UC大鼠模型。以柳氮磺胺吡啶(SASP)为阳性对照,同时联合使用PPAR-γ抑制剂双酚A-二甘氨酸醚(BADGE),给药7 d后病理检测各组大鼠结肠组织的损伤情况,并通过蛋白质印迹法(Western blot)和实时荧光定量多聚核苷酸链式反应(Real-time PCR)实验分别检测大鼠结肠组织中PPAR-γ、p38 MAPK的蛋白和基因表达,同时检测各组大鼠结肠组织中黏蛋白2(MUC2)和三叶因子3(TFF3)的表达情况。结果:清肠化湿方可上调TNBS大鼠结肠组织PPAR-γ的表达(P<0.01),同时抑制p38 MAPK的活性(P<0.01),并促进结肠组织中MUC2和TFF3表达(P<0.01),当联用PPAR-γ抑制剂BADGE后其对p38 MAPK的抑制作用减弱(P<0.05)。结论:清肠化湿方对TNBS大鼠结肠炎有明显的保护作用,其作用机制可能与激活PPAR-γ信号通路、抑制p38 MAPK的激活、减轻炎症反应、升高结肠组织中MUC2与TFF3的表达水平、参与肠黏膜的修复有关。Objective：To investigate the efficacy of Qingchang Huashi decoction（QHD） on ulcerative colitis induced by 2,4,6- trinitrobenzen sulfonic acid（TNBS） in Wistar rats and determine the expression of PPAR- γ and p38 MAPK in colonic mucosa of rats in further to study the function and mechanism of QHD in rats with ulcerative colitis. Methods：Eighty male Wistar rats were used to establish UC models and divided randomly into eight groups：the normal group,model group,QHD- low group,QHD- medium group,QHD- high group,SASP group,SASP＋ BADGE group and the QHD- medium＋ BADGE group. Each group had ten rats. TNBS was used in seven groups except for the normal group to establish ulcerative colitis model in rats. SASP and BADGE which were the inhibitors of PPAR- γ were used. After 7 days,the colonic pathological morphology was observed. Western blot and Real- time PCR（RT- PCR） were performed to detect the protein levels and m RNA levels of PPAR- γ and p38 MAPK. The expressions of MUC2 and TFF3 in colonic mucosa were also measured by RT- PCR. Results：Compared with the model group,QHD could effectively improve the life quality,reduce colon tissue inflammatory cells infiltration,enhance colonic mucosal tissue repair and promote the recovery of UC rats.QHD could increase PPAR- γ expression and inhibit p38 MAPK activity. In addition,QHD was able to increase significantly the expressions of MUC2 and TFF3 in colonic mucosa. Conclusion：QHD had obvious protective effect on UC. One of the mechanisms might be that QHD could active PPAR- γsignaling and inhibit p38 MAPK activation,increase the expression of MUC2 and TFF3 in colonic tissue to participate in restoration of intestinal mucosa,and inhibit the release of inflammatory cells.

关 键 词：清肠化湿方 溃疡性结肠炎 过氧化物酶体增殖物激活受体-Γ p38丝裂原活化蛋白激酶 黏蛋白2 三叶因子3 大鼠 

分 类 号：R285.5[医药卫生—中药学]