摘要
目的探讨p38丝裂原活化蛋白激酶(p38MAPK)在晚期妊娠合并急性胰腺炎(acute pancreatitis in pregnancy,APIP)相关胎鼠肾脏损伤中的作用及意义。方法 18只妊娠晚期SD妊娠大鼠随机分为3组,假手术(Sham-operation,SO)组、急性胰腺炎(acute pancreatitis,AP)组和p38MAPK抑制剂SB203580处理(SB)组。采用5%牛磺胆酸钠(sodium taurocholate,STC)逆行胰胆管注射法建立妊娠大鼠的APILP模型,SB组妊娠大鼠在建立APIP模型前0.5h给予SB203580腹腔注射(10mg/Kg·BW)。SO组妊娠大鼠仅在开腹后翻动暴露胰腺。SO组和AP组大鼠在开腹前0.5h给予对应体积的SB203580溶剂,各组大鼠均在术后12h剖杀取材。测定妊娠大鼠血清淀粉酶(AMY)和TNF-α的含量,光镜下观察胎鼠肾脏的病理学改变并进行评分。免疫组织化学法检测胎鼠肾脏中NF-κB、TNF-α和IL-1β的表达情况,Western Blot法检测胎鼠肾脏中pp38MAPK和p38MAPK的表达水平。结果与SO组比较,APILP组大鼠血清中AMY和TNF-α的含量显著升高,差异有统计学意义(P<0.05),胎鼠肾脏的病理评分显著升高,差异有统计学意义(P<0.05),胎鼠肾脏中NF-κB的表达量和核转位更为显著,差异有统计学意义(P<0.05),p-p38MAPK的表达水平显著升高,差异有统计学意义(P<0.05)。与APILP组比较,SB组大鼠血清中AMY和TNF-α的含量显著下降,差异有统计学意义(P<0.05),胎鼠肾脏的病理评分显著降低,差异有统计学意义(P<0.05),胎鼠肾脏中NF-κB表达量和核转位水平显著下降,差异有统计学意义(P<0.05),胎鼠肾脏中pp38MAPK的表达水平显著下降,差异有统计学意义(P<0.05)。结论 p38MAPK/NF-κB信号通路参与了APILP相关胎鼠肾脏损伤的过程;p38MAPK抑制剂SB203580对APILP相关胎鼠肾脏损伤具有保护作用,其机制可能与其下调p38MAPK的磷酸化,抑制NF-κB炎症信号通路激活有关。
Objective To investigate the role of p38MAPK in fetal kidney injury associated with acute panereatitis in late pregnancy （APIP）. Methods 18 pregnant SD rats were randomly divided into 3 groups, including Sham Operation （SO） group, APIP（AP） group, and SB203580 treatment （SB） group, with 6 rats in each group. APIP model was induced by retrograde injecting of 5 % sodium taurocholate into the biliary-pancreatic duct. Before APIP induction, the rats in SB group received 10 mg/Kg per 100g body- weight dissolved by dimethyl sulfoxide via intraperitoneal injection. Rats in SO and AP groups were intraperitoneally injected with same amount of solvent. All rats were sacrificed at 12 hours after operation, then the blood and tissue samples were harvested. Amylase and TNF-α in serum of maternal rats were analyzed. Histopathological changes of fetal kidney were observed and evaluated under light microscope. The expression and location of NF-κB in fetal kidney were analyzed by immunohistochemistry, as well as TNF-α and IL- 1β. The expression of p-p38MAPK, p38MAPK was determined by using western blot. Results Obvious pathological changes existed in fetal kidney after the attack of APIP, and their pathological scores were significant higher than that of SO group（P 〈 0. 05 ） , while the pathological injuries were ameliorated, and the scores decreased significantly in SB group（ P 〈 0. 05 ）. The level of AMY and TNF-α in maternal serum were markedly increased in the AP group, as well the expression of NF-κB,TNF-α, IL-1β and p-p38MAPK in fetal kidney（P 〈0. 05 ）. The transloeation of NF-κB was far more pervasive in the AP group than that of SO group （P 〈 0. 05 ）. Compared with the AP group, the levels of AMY and TNF-α in maternal serum decreased significantly （ P 〈 0. 05 ）, as well as the expression of NF-KB, TNF-α, IL-1β and p-p38MAPK in fetal kidney （P 〈 0. 05 ）. In addition, the transloeation of NF-κB was inhibited markedly. Conclusion p38MAPK played a vital role in the progress of fetal kidney injury associated with APIP, and the inhibition of phosphorylation level of p38MAPK by SB203580 ameliorated fetal kidney injury by interdicting inflammatory cascade.
作者
刘禹
李满
赵亮
王卫星
LIU Yu;LI Man;ZHAO Liang;WANG Weixing(Renmin Hospital of Wuhan University,Wuhan 430060,Chin)
出处
《公共卫生与预防医学》
2018年第4期10-15,共6页
Journal of Public Health and Preventive Medicine
基金
国家自然科学基金面上项目(81370562)
