BMSCs对IRI大鼠肾小管病理、ROCK蛋白水平的影响

Effect of BMSCs on renal tubular pathology and rock protein level in IRI mice

目的研究骨髓间充质干细胞(Bone Marrow Mesenchymal Stem Cells,BMSCs)移植对缺血再灌注损伤(Ischemia Reperfusion Injury,IRI)大鼠肾小管病理、Rho相关卷曲螺旋形成蛋白激酶(Rho Associated Coiled Coil Forming Protein Kinase,ROCK)蛋白水平的影响。方法把30只大鼠随机分为sham组、IRI组和BMSCs组,每组各10只。比较三组大鼠的生化指标和肾组织病理变化,观察三组大鼠肾小管上皮细胞的增殖和凋亡情况,最后比较三组大鼠肾组织中ROCK蛋白的表达情况。结果与sham组大鼠相比较,IRI组大鼠的血肌酐(Serum Creatinine,SCr)和尿素氮(Blood Urea Nitrogen,BUN)水平均显著增高(P<0.05);BMCSs组大鼠的SCr和BUN水平明显低于IRI组大鼠(P<0.05)。IRI组大鼠的肾小管出现严重损坏,肾小管管腔有明显的扩张现象,肾小管上皮细胞也出现肿胀和坏死的现象,管型呈红细胞或颗粒状,肾间质大量的出血和水肿。与IRI组大鼠比较,BMSCs组大鼠的肾单位损伤较轻,肾组织情况得到了明显的改善。与sham组大鼠肾小管上皮细胞中PCNA阳性表达比较,IRI组大鼠PCNA阳性表达显著降低(P<0.05);BMSCs组大鼠的阳性细胞数量显著多于IRI组大鼠。IRI组大鼠的凋亡细胞显著多于sham组,并且在细胞核中存在大量核固缩;BMSCs组大鼠的凋亡情况显著低于IRI组大鼠。与sham组大鼠比较,IRI组大鼠的RhoA蛋白和ROCKⅠ蛋白表达显著增加(P<0.05);BMSCs组大鼠的RhoA蛋白和ROCKⅠ蛋白表达显著低于IRI组(P<0.05)。结论BMSCs可有效的保护肾缺血再灌注损伤导致的肾小管损伤,同时抑制肾组织中ROCK蛋白表达,从而对肾脏起到保护作用。

Objective To investigate the effects of bone marrow mesenchymal stem cells(BMSCs)on renal tubular pathology and Rho associated coil forming protein kinase(ROCK)protein levels in rats with myocardial ischemia-reperfusion injury(IRI).Methods Thirty mice were divided into three groups:sham group,IRI group and BMSCs group.The biochemical indexes and pathological changes of renal tissue were compared among the three groups,and the proliferation and apoptosis of renal tubular epithelial cells were observed.Results The levels of serum creatinine(SCr)and Blood urea nitrogen(BUN)were significantly lower in group BMSCs than those in group IRI(P<0.05).The renal tubules of IRI group were seriously damaged,the lumen of renal tubules was obviously dilated,the epithelial cells of renal tubules were swollen and necrotic,the tubular type was red blood cells or granules,and the renal interstitium was also massive hemorrhage and edema.Compared with IRI group,the injury of nephron in BMSCs group was lighter,and the renal tissue condition was significantly improved.Compared with sham group,the positive expression of PCNA in IRI group was significantly lower than that in sham group(P<0.05);the number of positive cells in BMSCs group after transplantation was significantly more than that in IRI group.Compared with sham group,IRI group had more apoptotic cells than sham group,and there were a lot of pyknosis in nucleus;the apoptosis of BMSCs group was significantly lower than that of IRI group.Compared with of Ras homologous gene family(member a,RhoA)and Rho associated kinaseⅠ(ROCKⅠ)in sham group,the protein expression of IRI group was significantly increased(P<0.05);the expression of RhoA protein and ROCKⅠprotein in BMSCs group after transplantation was significantly lower than that in IRI group(P<0.05).Conclusion BMSCs can effectively protect renal tubular injury caused by renal ischemia-reperfusion injury and inhibit the expression of rock protein in renal tissue.