CAJ | 학술논문

目的探讨肾上腺髓质素(AM)在肠缺血再灌注损伤(I/R)中对肠黏膜屏障功能的影响及机制.方法将21只C57小鼠随机分为3组:(1)Sham组;(2) I/R组;(3) I/R+ AM组.采用夹闭肠系膜上动脉30 min、再灌注6h作为制备肠缺血再灌注损伤模型的方法.用苏木素-伊红(HE)染色的方法观察肠黏膜的损伤;测定小肠肠黏膜的跨上皮电阻(TER);检测紧密连接蛋白ZO-1和Claudin-1蛋白水平的变化以及信号分子727位丝氨酸磷酸化的信号转导与转录激活子1[p-STAT1(S727)]在各组中的激活.结果 HE染色结果显示肠I/R引起部分小肠绒毛上皮脱落,经AM预处理使得小肠绒毛重新排列整齐,显著缓解肠I/R所致的形态结构破坏.肠I/R引起ZO-1和Claudin-1的蛋白表达水平较Sham组分别下降38.54％及42.98％,并引起TER降低44.57％;经AM预处理使得ZO-1和Claudin-1的蛋白的表达较I/R组显著升高(分别为31.33％、33.92％),同时TER值较肠I/R组升高25.97％,并且使得肠I/R所致的p-STAT1(S727)激活被显著抑制(较I/R组降低56.52％).结论 AM对小鼠肠I/R损伤后肠黏膜屏障具有较好的保护作用,并且可以调控肠道紧密连接蛋白的表达,进而影响肠道通透性的改变,其机制可能与抑制p-STAT1(S727)的激活有关.
목적 탐토신상선수질소(AM)재장결혈재관주손상(I/R)중대장점막병장공능적영향급궤제.방법 장21지C57소서수궤분위3조:(1)Sham조;(2) I/R조;(3) I/R+ AM조.채용협폐장계막상동맥30 min、재관주6h작위제비장결혈재관주손상모형적방법.용소목소-이홍(HE)염색적방법관찰장점막적손상;측정소장장점막적과상피전조(TER);검측긴밀련접단백ZO-1화Claudin-1단백수평적변화이급신호분자727위사안산린산화적신호전도여전록격활자1[p-STAT1(S727)]재각조중적격활.결과 HE염색결과현시장I/R인기부분소장융모상피탈락,경AM예처리사득소장융모중신배렬정제,현저완해장I/R소치적형태결구파배.장I/R인기ZO-1화Claudin-1적단백표체수평교Sham조분별하강38.54％급42.98％,병인기TER강저44.57％;경AM예처리사득ZO-1화Claudin-1적단백적표체교I/R조현저승고(분별위31.33％、33.92％),동시TER치교장I/R조승고25.97％,병차사득장I/R소치적p-STAT1(S727)격활피현저억제(교I/R조강저56.52％).결론 AM대소서장I/R손상후장점막병장구유교호적보호작용,병차가이조공장도긴밀련접단백적표체,진이영향장도통투성적개변,기궤제가능여억제p-STAT1(S727)적격활유관.
Objective To investigate the effect of adrenomedullin on intestinal mucosal barrier function in a mouse model of intestinal ischemia/reperfusion Methods Twenty-one C57BL/6 mice were randomly divided into Sham group,ischemia/reperfusion (I/R) group and I/R + AM group.the superior mesenteric artery (SMA) was occluded for 30 min using nontraumatic vascular clamps,followed by reper-fusion for 6 h.Then sections were obtained for hematoxylin-eosin (HE) staining,to observe the morpho-logical changes of intestinal mucosa.Ussing chambers was used to detection of intestinal permeability (TER).The protein expressions of tight junction proteins (ZO-1 and Claudin-1) were examined by using Western blotting,the activation of p-STAT1 (S727) was also assayed.Results HE staining showed intestinal I/R caused part of villus epithelial shedding,after AM pretreatment the villus in the small intestine rearranged in neat rows,attenuated the disruption of intestinal morphological structure caused by intestinal I/R.The protein expressions of ZO-1 and Claudin-1 in I/R group were significantly decreased by 38.54％and 42.98％ respectively when compared with that in Sham group (P ＜ 0.01).The TER value in I/R group was decreased by 44.57％ as compared with Sham group (P ＜ 0.05) After AM pretreatment,the protein expression of ZO-1 and Claudin-1 protein expression were significantly raised compared to that in I/R group (by 31.33％,33.92％).Simultaneously,TER in I/R + AM group was significantly raised as compare with I/R group by 25.97％.And Intestinal I/R induced p-STAT1 (S727) activation was significantly inhibited.(decreased as compared with I/R group by 56.52％) Conclusion AM can attenuate intestinal mucosal barrier dysfunction by regulating the expression of intestinal tight junction proteins.The inhibition of p-STAT1 (S727) activation may be involved in this mechanism.