PGE_(2)在环氧合酶-2抑制剂保护脓毒症肠屏障功能中的作用  

Role of PGE_(2) in cyclooxygenase-2 inhibitor protecting intestinal barrier function in sepsis

作　　者：刘志慧[1] 张桂利[1] 王燕燕 卢鼎 李淑凡 张存宇 王姣姣 张子怡 Liu Zhihui;Zhang Guili;Wang Yanyan;Lu Ding;Li Shufan;Zhang Cunyu;Wang Jiaojiao;Zhang Ziyi(Department of Anesthesiology,Baotou Central Hospital,Baotou 014040,Inner Mongolia,China;Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014040,Inner Mongolia,China;Inner Mongolia Medical University,Hohhot 010100,Inner Mongolia,China.)

机构地区：[1]包头市中心医院麻醉科,内蒙古包头014040 [2]内蒙古科技大学包头医学院,内蒙古包头014040 [3]内蒙古医科大学,内蒙古呼和浩特010100

出　　处：《贵州医药》2024年第2期171-175,179,共6页Guizhou Medical Journal

基　　金：内蒙古自然科学基金(2017BS0802);内蒙古医科大学联合项目(YKD2021LH063)。

摘　　要：目的探讨PGE_(2)在环氧合酶-2抑制剂保护脓毒症肠屏障功能中的作用及机制。方法按随机数字表法将大鼠分为六组,假手术组、帕瑞昔布钠对照组、脓毒症组、帕瑞昔布钠治疗组、COX-2抑制剂组和帕瑞昔布钠-COX-2抑制剂组,每组8只。采用盲肠结扎穿孔术(CLP)制备脓毒症模型,ELISA检测大鼠血清和肠组织中TNF-α、IL-6水平和抗炎细胞因子IL-10水平,蛋白质免疫印迹试验(Western Blot)检测前列腺素E_(2)(PGE_(2))、前列腺素合酶-1(mPGES-1)和前列腺素受体EP4的蛋白表达,于假手术或CLP术后24 h取四组大鼠肠组织,RT-PCR法检测PGE_(2)、mPGES-1、EP4的mRNA表达水平。结果与假手术组比较,脓毒症大鼠血清和肠组织中TNF-α、IL-6和IL-10增加(P<0.05),帕瑞昔布钠治疗后能够降低TNF-α、IL-6水平(P<0.05),IL-10水平增加(P<0.05);术后24 h时脓毒症组大鼠肠组织PGE_(2)、mPGES-1、EP4和EP2 mRNA表达水平比假手术组明显升高,差异有统计学意义(P<0.05);与脓毒症组比较,帕瑞昔布钠治疗脓毒症大鼠后,肠组织PGE_(2)、mPGES-1、EP4的mRNA水平明显降低,差异有统计学意义(P<0.05);大鼠肠组织前列腺素E_(2)(PGE_(2))、前列腺素合酶-1(mPGES-1)和前列腺素受体EP4的蛋白表达水平比假手术组明显升高,差异有统计学意义(P<0.05),帕瑞昔布钠治疗后,肠组织前列腺素E_(2)(PGE_(2))、前列腺素合酶-1(mPGES-1)和前列腺素受体EP4的蛋白表达水平明显降低,差异有统计学意义(P<0.05);术后24h时,与假手术组比较,脓毒症组、帕瑞昔布钠治疗组、COX-2抑制剂组及帕瑞昔布钠-COX-2抑制剂组肠组织TNF-α、IL-10和IL-6的水平明显升高,差异有统计学意义(P<0.05);与脓毒症组比较,帕瑞昔布钠治疗组、COX-2抑制剂组及帕瑞昔布钠-COX-2抑制剂组肠组织TNF-α、IL-6的水平明显降低,IL-10的水平明显升高,差异有统计学意义(P<0.05);与帕瑞昔布钠治疗组比较,COX-2抑制剂组及帕瑞昔布钠-COX-Objective To investigate the role and mechanism of PGE_(2) in the protection of intestinal barrier function by cyclooxygenase-2 inhibitor in sepsis.Methods Male Wistar rats were randomly divided into 6 groups which were sham operation group,parecoxib sodium control group,sepsis group,parecoxib sodium treatment group,COX-2 inhibitor group and parecoxib sodium-cox-2 inhibitor group,with 8 rats in each group.Sepsis model was established by cecal ligation and perforation(CLP).TNF-α,IL-6 and IL-10 in serum and intestinal tissue was detected by ELISA.The protein expressions of prostaglandin E_2(PGE_2),prostaglandin synthase-1(mPGES-1) and prostaglandin receptor EP4 were detected by Western blot(WB).The mRNA expression levels of PGE_2,mPGES-1 and EP4 were detected by RT-PCR.Results Compared with the sham operation group,TNF-α,IL-6 and IL-10 were increased in serum and intestinal tissue of septic rats(P<0.05),and TNF-α,IL-6 level(P<0.05) were significantly decreased,IL-10 level was increased in parecoxib sodium treatment group(P<0.05).The expression levels of PGE_2,mPGES-1,EP4 and EP2 mRNA in sepsis group were significantly higher than those in sham operation group(P<0.05).Compared with sepsis group,the mRNA levels of PGE_2,mPGES-1 and EP4 in intestinal tissue of sepsis rats treated with parecoxib sodium decreased significantly(P<0.05).The protein expression levels of prostaglandin E_2(PGE_2),prostaglandin synthase-1(mPGES-1) and prostaglandin receptor EP4 in intestinal tissue of rats were significantly higher than those in sham operation group(P<0.05).After parecoxib sodium treatment,the protein expression levels of prostaglandin E_2(PGE_2),prostaglandin synthase-1(mPGES-1) and prostaglandin receptor ep4 in intestinal tissue were significantly lower,there were statistically significant differences(P<0.05).Compared with the sham operation group,the levels of TNF-α,IL-10 and IL-6 were increased significantly in sepsis group,parecoxib sodium treatment group,COX-2 inhibitor group and parecoxib sodium-cox-2 inhibitor gro

关 键 词：前列腺素E_(2) COX-2抑制剂 脓毒症 肠屏障 

分 类 号：R363[医药卫生—病理学]