CAJ | 학술논문

目的观察纤维蛋白肽Bβ15～42(the fibrin-derived peptide 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3.6 mg/kg; FgBβ15～42肽治疗组:于肾脏再灌注后立即尾静脉注射FgBβ15～ 42肽3.6 mg/kg.后3组按照再灌注24h、48 h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48 h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ICA M-1的mRNA和蛋白水平于再灌注24h显著上升,48 h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-1β和ICAM-1的表达于再灌注24h、48 h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.
목적 관찰섬유단백태Bβ15～42(the fibrin-derived peptide Bβ15-42,FgBβ15～42태)대대서신장결혈재관주손상(IRI)후신장국부염성반응적영향병탐토기궤제.방법 장SD대서수궤분성가수술조(Sham조)、IRI조、음성치료조화FgBβ15 ～ 42태치료조.Sham조:분리신동맥후관폐복강;IRI조:채용쌍측신동맥협폐적방법제작신장IRI모형;음성치료조:우신장재관주후립즉미정맥주사수궤태단3.6 mg/kg; FgBβ15～42태치료조:우신장재관주후립즉미정맥주사FgBβ15～ 42태3.6 mg/kg.후3조안조재관주24h、48 h분위량개아조,Sham조여각아조균위8지대서.상규생화법검측신공능;HE、PAS염색관찰신장조직학개변;면역조화、실시형광정량PCR법급Western인적검측신조직백세포개소1β(IL-1β)、세포간점부분자1(ICAM-1)적mRNA급단백표체.결과 여Sham조상비,IRI조적Scr화BUN수평균현저증가(균P ＜0.05),신소관급간질병리손상현저,이재관주48 h경위명현;여IRI조상비,FgBβ15～ 42태치료조Scr화BUN현저하강(균P＜0.05),소관간질손상정도명현감경(P＜0.05).여Sham조상비,IRI조IL-1β화ICA M-1적mRNA화단백수평우재관주24h현저상승,48 h초미하강,단잉유지재교고수평;FgBβ15～ 42태치료조대서신조직IL-1β화ICAM-1적표체우재관주24h、48 h현저저우동시간점적IRI조(균P＜0.05),단잉명현고우Sham조.상술각지표재음성치료조화IRI조지간적표체차이무통계학의의.결론 FgBβ15～42태대신장IRI구유보호작용,기작용궤제가능여기감소염성인자IL-1β、점부분자ICAM-1적표체유관.
Objective To investigate the effects of the fibrin-derived peptide Bβ15-42 (FgBβ 15-42) 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 immunohistochemistry,real-time PCR and Western blotting.Results Compared with sham group,Scr and BUN were obviously increased in IRI 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-1 β in the kidney.