人脐带间充质干细胞减缓阿霉素诱导的FSGS小鼠损伤及对TGF-β1/Smad表达的影响  

Human umbilical cord mesenchymal stem cells alleviate adriamycin-induced injury in FSGS mice via regulation of the TGF-β1/Smad signaling pathway

作　　者：陈方旭 米焱[1] 南蕾[1] 王彩丽[1] CHEN Fang-xu;MI Yan;NAN Lei;WANG Cai-li(Department of Nephrology,the First Affiliated Hospital of Baotou Medical College,Baotou 014000,China)

机构地区：[1]包头医学院第一附属医院肾内科,包头014000

出　　处：《现代免疫学》2023年第3期218-225,共8页Current Immunology

基　　金：国家自然科学基金(81760135)。

摘　　要：为研究人脐带间充质干细胞(human umbilical cord mesenchymal stem cell, HU-MSC)移植对局灶性节段性肾小球硬化(focal segmental glomerulosclerosis, FSGS)小鼠肾脏损伤的修复作用,并探索在该修复过程中TGF-β1/Smad信号通路的表达情况,将8周龄雄性BALB/c小鼠随机分为FSGS组、FSGS+HU-MSC组和对照组,FSGS组和FSGS+HU-MSC组在试验第1天以10.5 mg/kg体质量的剂量一次性给与尾静脉注射阿霉素;FSGS+HU-MSC组在试验第33、40、47、54、61天给与尾静脉注射HU-MSC悬液(2×10^(6)个细胞), FSGS组在相同时间给与尾静脉注射等量的生理盐水;对照组为正常小鼠,不给与任何干预措施。于第7、14、28、54、68天分别测定小鼠体质量和尿白蛋白;于第28、68天处死小鼠,眼眶取血并检测其血清肌酐、尿素氮水平,取肾脏标本并观察其肾脏病理表现,采用免疫组化法检测TGF-β1、Smad3、Smad7蛋白表达水平。结果显示,FSGS+HU-MSC组、FSGS组与对照组比较,小鼠体质量显著减少(P<0.001),尿白蛋白、血肌酐、尿素氮水平均显著升高(P<0.01);而FSGS+HU-MSC组较FSGS组体质量显著增加(P<0.01),尿白蛋白、血肌酐、尿素氮水平均显著降低(P<0.01)。FSGS+HU-MSC组与FSGS组比较,肾脏病理损伤程度明显减轻。免疫组化结果显示,FSGS+HU-MSC组和FSGS组较对照组TGF-β1、Smad3表达水平显著升高(P<0.001), Smad7表达水平显著降低(P<0.001);而FSGS+HU-MSC与FSGS组比较,TGF-β1和Smad3表达水平显著降低(P<0.001), Smad7表达水平显著升高(P<0.001)。该研究提示,HU-MSC对阿霉素诱导的FSGS有修复作用,其机制可能与调控TGF-β1/Smad信号通路有关。This study proposes to investigate the effect of human umbilical cord mesenchymal stem cell(HU-MSC)transplantation on the repair of renal injury in mice with focal segmental glomerulosclerosis(FSGS),and explore the expression of TGF-β1/Smad signaling pathway during the repair process.To this end,8-week male BALB/c mice were randomly divided into the FSGS group,FSGS+HU-MSC group,and control group.FSGS group and FSGS+HU-MSC group were given adriamycin intravenously at 10.5 mg/kg on day 1.Subsequently,the FSGS+HU-MSC group was injected with HU-MSC suspension(2×10^(6) cells)in the caudal vein on day 33,40,47,54,and 61,respectively while the FSGS group was injected with saline.The normal control group did not receive any treatment.Body weight and urinary albumin were measured on day 7,14,28,54,and 68,respectively.On day 28 and 68,the mice were sacrificed.Blood from orbit and kidney samples were collected to detect serum creatinine and urea nitrogen.In addition,renal pathology was observed and the protein expressions of TGF-β1,Smad3,and Smad7 were detected by immunohistochemistry.The results showed that compared to the control group,the body weight of the FSGS+HU-MSC group and the FSGS group was significantly decreased(P<0.001),and the levels of urinary albumin,serum creatinine,and urea nitrogen were significantly increased(P<0.01).Interestingly,compared to the FSGS group,the body weight of FSGS+HU-MSC group was significantly increased(P<0.01),and the levels of urinary albumin,serum creatinine,and urea nitrogen were significantly decreased(P<0.01).Renal pathological damage in the FSGS+HU-MSC group was significantly reduced compared to that in the FSGS group.Immunohistochemical results showed that TGF-β1 and Smad3 expressions were significantly increased in the FSGS+HU-MSC group and the FSGS group compared to those in the control group(P<0.001),while Smad7 expression was significantly decreased(P<0.001).Compared to the FSGS group,the FSGS+HU-MSC group exhibited significant decrease in TGF-β1 and Smad3 expressions(P

关 键 词：人脐带间充质干细胞 阿霉素 局灶性节段性肾小球硬化 转化生长因子Β 

分 类 号：R692.6[医药卫生—泌尿科学]