骨髓间充质干细胞对肾缺血再灌注损伤后肾功能及氧化应激水平的改善作用

Improvement of bone marrow mesenchymal stem cells on kidney function and level of oxidative stress after renal ischemia-reperfusion injury

目的:探讨骨髓间充质干细胞(BMSCs)促肾缺血再灌注损伤修复的能力,为肾脏疾病治疗提供新的思路。方法:健康3周龄C57BL/6J小鼠的骨髓细胞悬液进行BMSCs体外扩增培养。8周龄C57BL/6J小鼠随机分为假手术组、平行对照组和细胞移植组,每组16只小鼠。建立肾缺血-再灌注损伤模型,将BMSCs通过尾静脉注射到细胞移植组小鼠中,平行对照组注射生理盐水。检测肾功能指标血尿素氮(BUN)和肌酐(Cr)水平变化、损伤肾组织自由基——羟自由基和超氧阴离子自由基变化和肾形态学变化。结果:①分离培养的BMSCs增殖旺盛,纯度较高,且均质性和稳定性好。②平行对照组小鼠整体状态差,肾功能指标、氧化应激指标明显升高,组织形态学出现肾小球崩解,肾小管结构消失,肾间质见大量炎性细胞浸润。而细胞移植组小鼠整体状态良好,肾功能指标和氧化应激指标得到明显改善(P<0.05),组织形态学未出现明显病理性改变。结论:BMSCs在体外易分离培养,具有旺盛的增殖能力;移植BMSCs后,通过抑制氧自由基的生成来促进肾缺血-灌注损伤后小鼠的恢复。

Objective To study the capability of bone marrow mesenchymal stem cells（BMSCs） in promoting the recovery of renal ischemia-reperfusion injury and provide a new method for the treatment of renal diseases.Methods BMSCs were cultivated and amplified in vitro from bone marrow cell suspension of healthy 3-week-old C57BL/6J mice.8-week-old C57BL/6J mice were randomly divided into sham operation group（n=16）,parallel control group（n=16） and cell transplantation group（n=16）.The renal ischemia-reperfusion injury model was established.BMSCs were transplanted into the mice in cell transplantation group via the tail vein and saline was injected into the mice in parallel control group.Renal function,such as the level of serum urea nitrogen（BUN） and creatinine（Cr）,the indexes of renal oxidative stress,such as the levels of hydroxyl radical and superoxide anion,morphologic changes and renal pathological changes were detected.Results ①BMSCs not only had a high purification,homogeneity and stability,but also had unlimited proliferation.②The mice in parallel control group appeared the poor state.The indexes of renal function and oxidative stress were obviously increased.And there were collapse of renal glomerulus,disappearance of renal tubule and infiltration of inflammatory cells in renal tissue.Transplanted mice appeared the good state.The indexes of renal function and indexes of oxidative stress had been significantly improved（P〈0.05）.The renal pathological changes were not obvious.Conclusion BMSCs are easily isolated and cultivated in vitro.BMSCs can improve renal ischemia-reperfusion injury via vein transplantation by inhibiting the production and attacking of oxygen free radicals.