脂肪源间充质干细胞对小鼠急性肾损伤后干细胞因子及其受体表达的影响

Effect of adipose-derived mesenchymal stem cells on expression of stem cell factor and receptor in acute kindey injury of mice

目的研究脂肪源间充质干细胞(ADMSCs)对急性肾损伤(AKI)的治疗作用,并探讨ADMSCs治疗小鼠AKI可能的机制。方法 30只雄性昆明小鼠随机分为正常对照组、模型组和治疗组,每组10只。应用腹腔注射顺铂建立AKI模型,治疗组于注射顺铂12 h后尾静脉注射ADMSCs悬液,模型组于注射顺铂12 h后尾静脉注射等量生理盐水。注射顺铂7 d后处死小鼠,通过测定血清尿素氮(BUN)和血肌酐(Scr)水平及观察小鼠肾组织形态学改变判断肾损伤情况;免疫组织化学法检测中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、干细胞因子受体(c-KIT)及干细胞因子(SCF)表达情况。结果与模型组比较,治疗组BUN、Scr和NGAL水平显著下降(P<0.01),肾小管坏死(ATN)评分显著降低(P<0.01),c-KIT、SCF表达显著增加(P<0.01);与正常对照组比较,模型组c-KIT、SCF表达亦显著增加(P<0.01)。结论在AKI小鼠模型中,外源性ADMSCs可能通过旁分泌SCF、c-KIT,并激活SCF/c-KIT信号通路来促进肾小管细胞的修复,继而达到保护受损肾脏的作用。

Objective To study the therapeutical effect of adipose-derived mesenchymal stem cells（ADMSCs） on the acute kidney injury（AKI） and to investigate its possible mechanism.Methods Thirty male Kunming rats were divided into normal control group,model group and treatment group randomly with 10 rats in each group.The AKI model was set up by cisplatinum intraperitoneal injection.ADMSCs suspension was injected into caudal vein in treatment group in 12 hours after cisplatinum intraperitoneal injection while the same equivalent normal saline was injected into caudal vein in normal control group.The mice were sacrificed 7 days after the cisplatinum intraperitoneal injection.The condition of kidney injury was judged by observing the morphological changes of their nephridial tissue and measuring the levels of blood urea nitrogen（BUN） and serum creatinine（Scr）.The expression of neutrophil gelatinase-associated lipocalin（NGAL）,c-KIT and stem cell factor（SCF）were measured by immunohistochemical method.Results Compared with the model group,the levels of BUN,Scr and NGAL and the renal tubular necrosis（ATN） score decreased significantly while the expression of c-KIT and SCF increased significantly in the treatment group（P〈 0.01）.Compared with the normal control group,the levels of c-KIT and SCF in the treatment group were increased significantly（P〈 0.01）.Conclusion In the model of AKI,exogenous ADMSCs can enhance the function of repairion for the injured renal tubular epithelial cell to protect the injured kidney by the paracrine of SCF,c-KIT and its activating of SCF /c-KIT.