清下化瘀方改善重症急性胰腺炎大鼠肠黏膜屏障功能及对p38MAPK/ATF2信号通路的影响  

Qingxia Huayu Recipe Improved Intestinal Barrier Function in Acute Pancreatitis Rats and Its Effects on p38MAPK/ATF2 Signal Pathway

作　　者：孔婧[1,2] 王晓素[1,2] 周秉舵[1,2] 李英[1] 徐亭亭[1] KONG Jing;WANG Xiao-su;ZHU Bing-duo;LI Ying;XU Ting-ting(Department of Digestion,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Chinese Medicine,Shanghai,200437;Institute of Gastroenterology,Shanghai University of Chinese Medicine,Shanghai,200437)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院消化内科,上海200437 [2]上海中医药大学脾胃病研究所,上海200437

出　　处：《中国中西医结合杂志》2019年第11期1372-1377,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：上海市教委重点学科项目(No.J50305);上海市中西医临床协作试点建设项目(No.ZY2018-2020-FWTX-1004)

摘　　要：目的探讨清下化瘀方通过改善肠屏障功能治疗急性胰腺炎的作用机制。方法雄性SD大鼠50只按随机数字表法分为5组:假手术组、模型组、清下化瘀方组(简称中药组)、醋酸奥曲肽注射液(善宁)组、空白组,每组10只。采用逆胆胰管注射牛磺胆酸钠的方法建立重症急性胰腺炎大鼠模型,分别予清下化瘀方及善宁干预后取材,观察胰腺病理损伤程度及检测大鼠肠黏膜屏障功能改变(肠黏膜上皮损伤程度),并分析p38MAPK/ATF2表达的变化。结果(1)胰腺组织病理损伤:与空白组及假手术组比较,模型组大鼠胰腺病理总积分明显升高(P<0.01),提示造模成功。与模型组比较,清下化瘀方中药组及善宁组胰腺病理变化半定量积分明显降低(P<0.01)。(2)肠上皮损伤程度比较:与空白组及假手术组比较,模型组肠黏膜损伤明显增加(P<0.01),而中药组及善宁组对肠黏膜损伤有改善作用(P<0.01)。中药组与善宁组比较差异无统计学意义(P>0.05)。(3)肠屏障功能变化:空白组及假手术组肠黏膜上皮细胞表面微绒毛排列整齐,实验各组回肠出现不同程度的线粒体肿胀,嵴不清,内质网肿胀,上皮细胞微绒毛脱落,上皮细胞连接增宽。(4)p38MAPK/ATF2表达变化:模型组大鼠胰腺组织p38MAPK、ATF2阳性表达较空白组及假手术组明显升高(P<0.01),中药及善宁组表达较模型组显著降低(P<0.01)。结论清下化瘀方作用于SAP的途径可能与减轻重症急性胰腺炎大鼠的肠黏膜屏障的损伤,从而调控p38MAPK/ATF2表达,减轻机体炎症反应有关。Objective To observe the mechanism of Qingxia Huayu Recipe(QXHYR)in treating severe acute pancreatitis(SAP)rats by improving intestinal barrier function.Methods Totally 50 male SD rats were randomly divided into 5 groups,i.e.,a sham-operation group,a model group,QXHYR group,Shanning(SN)group,and a blank group,10 rats in each group.The SAP rat model was induced by retrograde injection of sodium taurocholate into the biliopancreatic duct,which were intervened by QXHYR and SN.The degree of intestinal mucosal injury and changes of rat intestinal mucosa barrier permeability were observed and detected,and changes of p38 MAPK/ATF2 expressions analyzed.Results(1)Pathological injury of pancreatic tissues:Compared with the blank group and the sham-operation group,the total pathological score of pancreas increased significantly in the model group(P<0.01),suggesting that the model was successfully established.Compared with the model group,the semi-quantitative integral of pancreatic pathological changes was significantly lower in the QXHYR group and the SN group(P<0.01).(2)Intestinal epithelial injury index:Compared with the blank group and the sham-operation group,intestinal mucosal injury was significantly aggravated in the model group(P<0.01).But it was attenuated in the QXHYR group and the SN group(P<0.01).The curative effects of QXHYR and SN were similar(P>0.05).(3)Changes of intestinal barrier function:Routine transmission electron microscope showed that intestinal mucosal epithelial cell surface microvilli were arranged in neat rows in the blank group and the sham-operation group.Swelling of mitochondria and unclear crest appeared to different degrees in the ileum of three experimental groups.Endoplasmic reticulum was swollen.The microvilli of epithelial cells was shedding and the junction of epithelial cells was widened.(4)Changes of P38 MAPK/ATF2 expressions:Higher positive expressions of p38 MAPK and ATF2 occurred in pancreas tissue of the model group than in that of the blank group and the sham-operation group(P<0

关 键 词：重症急性胰腺炎 清下化瘀方 肠黏膜屏障 p38MAPK/ATF2 

分 类 号：R[医药卫生]