纤维蛋白肽Bβ15～42对大鼠缺血再灌注损伤肾脏局部炎性反应的影响  

Effects of the fibrin- derived peptide Bβ15- 42 on renal inflammation after renal ischemia reperfusion injury in rats

作　　者：张琼[1] 乔玉峰[2] 石媛媛[2] 马月宏[3] 邵金金[2] 李荣山[1] 

机构地区：[1]山西医科大学附属人民医院(山西省人民医院)肾内科山西省肾脏病研究所,太原030012 [2]山西医科大学第二医院肾内科 [3]山西医科大学附属人民医院(山西省人民医院)中心实验室,太原030012

出　　处：《中华肾脏病杂志》2015年第7期527-533,共7页Chinese Journal of Nephrology

基　　金：国家自然科学基金应急管理项目（81450033）;山西省国际科技合作项目（2014081054）;山西高校科技研究开发项目（20091178）

摘　　要：目的观察纤维蛋白肽Bβ15—42（the fibrin—derivedpe ptide Bβ15-42，FgBβ15～42肽）对大鼠肾脏缺血再灌注损伤（IRI）后肾脏局部炎性反应的影响并探讨其机制。方法将SD大鼠随机分成假手术组（Sham组）、IRI组、阴性治疗组和FgBβ15～42肽治疗组。Sham组：分离肾动脉后关闭腹腔；IRI组：采用双侧肾动脉夹闭的方法制作肾脏IRI模型；阴性治疗组：于肾脏再灌注后立即尾静脉注射随机肽段3．6mg／kg；FgBβ15～42肽治疗组：于肾脏再灌注后立即尾静脉注射FgBβ15～42肽3．6mg／kg。后3组按照再灌注24h、48h分为两个亚组，Sham组与各亚组均为8只大鼠。常规生化法检测肾功能；HE、PAS染色观察肾脏组织学改变；免疫组化、实时荧光定量PCR法及Western印迹检测肾组织白细胞介素1β（IL-1β）、细胞间黏附分子1（ICAM-1）的mRNA及蛋白表达。结果与Sham组相比，IRI组的Scr和BUN水平均显著增加（均P〈0．05），肾小管及间质病理损伤显著，以再灌注48h更为明显；与IRI组相比，FgBβ15～42肽治疗组Scr和BUN显著下降（均P〈0．05），小管间质损伤程度明显减轻（P〈0．05）。与Sham组相比，IRI组IL-1β和ICAM-1的mRNA和蛋白水平于再灌注24h显著上升，48h稍微下降，但仍维持在较高水平；FgBβ15～42肽治疗组大鼠肾组织IL-1B和ICAM-1的表达于再灌注24h、48h显著低于同时间点的IRI组（均P〈0．05），但仍明显高于Sham组。上述各指标在阴性治疗组和IRI组之间的表达差异无统计学意义。结论FgBβ15～42肽对肾脏IRI具有保护作用，其作用机制可能与其减少炎性因子IL-1β、黏附分子ICAM-1的表达有关。Objective To investigate the effects of the fibrin-derived peptide Bβ15-42 （FgBβ15-42） on renal inflammation in acute kidney injury （AKI） induced by renal ischemia reperfusion （IR）. Methods SD rats were randomly divided into sham group （the abdominal cavity were closed after separating the renal artery）, IRI group （renal arteries of rats were occluded with microvascular clamps for 60 min）, negative treated group （rats were injected with 3.6 mg/kg random peptide by tail vein） and FgBβ15-42 treated group （rats were injected with 3.6 mg/kg FgBβ15- 42 by tail vein）. Rats were sacrificed at 24 h or 48 h after reperfusion. Blood and kidney samples were collected and histological changes and renal function were examed. The mRNA and protein expressions of intercellular cell adhesion molecule- 1 （ICAM-1） and interleukin-1β （IL-1β） were examined by immunohistoehemistry,real-time PCR and Western blotting. Results Compared with sham group, Scr and BUN were obviously increased in IR1 group （all P 〈 0.05）, pathologic changes of kidney were more serious （P 〈 0.05）. Compared with IRI group, in FgBβ15-42 treated group Scr and BUN were obviously decreased （all P 〈 0.05）, the injury of kidney tubulointerstitial was less serious （P 〈 0.05）. Compared with sham group, there was increased ICAM-1 and IL-1β in IRI group （all P 〈 0.05）, and they all peaked at 24 h. After treated with FgBβ15-42, the expression of ICAM- 1, IL-1β were significantly decreased in kidneys compared to IRI group （all P 〈 0.05）. The above indexes had no significant differences between negative treated group and IRI group （all P 〉 0.05）. Conclusions FgBβ15-42 can protect kidneys against ischemia reperfusion injury in rats. The mechanism may be associated with down- regulated expressions of ICAM- 1 and IL- 1β in the kidney.

关 键 词：再灌注损伤 炎症 肾功能不全 急性 纤维蛋白肽B 

分 类 号：R965[医药卫生—药理学]