人脐带间充质干细胞延缓大鼠肾脏衰老的作用

Study of anti-aging effects of human umbilical cord mesenchymal stem cells on rat kidney

目的:观察人脐带间充质干细胞(hUC-MSCs)移植对大鼠肾脏衰老的影响,探讨其可能的抗衰老机制.方法:将24只SD大鼠随机均分为3组,对照组、低剂量MSCs治疗组和高剂量MSCs治疗组.实验结束后取大鼠血清,ELISA测定大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)和晚期氧化蛋白产物(AOPP).HE染色观察大鼠肾脏病变程度,脂褐素染色观察肾脏衰老情况.结果:与对照组相比,氧化应激指标AOPP、MDA浓度明显下降(P<0.05),SOD活性明显升高(P<0.05),而低剂量组和高剂量组之间对比无明显差异(P>0.05).对照组与治疗组肾小球病变程度无显著差异(P>0.05),肾小管病变程度有显著性差异(P<0.05).大鼠肾脏脂褐素染色阳性主要分布于肾小管及间质,染色阳性面积比例治疗组较对照组明显降低(P<0.05),而两治疗组之间对比无显著性差异(P>0.05).RT-PCR检测大鼠肾脏p16INK4a mRNA的表达结果显示治疗组低于对照组(P<0.05),Western blot结果显示,治疗组p16INK4a蛋白表达较对照组明显减少(P<0.05).结论:人脐带间充质干细胞静脉移植能延缓老年大鼠肾脏功能减退,减少大鼠氧化应激终产物,提升抗氧化应激能力,减轻肾脏病理改变,减少脂褐素沉积,并能使衰老相关的p16INK4a mRNA及蛋白表达减少.

Objective：To study the effects of human umbilical MSCs） transplantation on the aging of rat kidney and to explore its cord mesenchymal stem cells （hUC- anti-aging mechanisms. Methods： 24 Sprague-Dawley rats were randomly divided into three groups： control, low-dose MSCs and high-dose MSCs groups. The serum was taken for measurement of superoxide dismutase （SOD） , malondialdehyde （ MDA）, and advanced oxidation protein products （AOPP）. The kidneys were harvested for examination of renal lesions, lipofuscin staining and hUC-MSCs tracing. Results： Compared to the control group, the oxidative stress indicators AOPP and MDA levels in treated groups decreased significantly （P 〈 0. 05 ）,SOD activity increased （P 〈 0.05 ）, whereas there was no significant difference between the two treatment groups （P 〉 0.05 ）. There was no significant difference in glomerular lesions between the control group and treatment groups （ P 〉 O. 05 ）, but there was a significant difference in renal tubular lesions （P 〈 0. 05 ）. Lipofuscin staining of rat kidney tissues was mainly observed in the renal tubules and interstitium. The staining areas in the treated groups were significant smaller than in the control group （P 〈 0. 05 ）. pl6INK4a mRNA expression in the rat kidney of treated groups was lower than in the control group （P 〈 0.05 ）, and the pl6INK4a protein expression in treated groups was significantly reduced （P 〈 0. 05 ）. There was no significant difference between the low-dose and high-dose groups （P 〉 0. 05）. Conclusion： Human umbilical cord mesenchymal stem cells intravenous transplantation to the aging rats could improve the renal functions, reduce oxidative stress end products, enhance anti-oxidative stress, reduce renal pathological lesions, reduce lipofuscin deposition, and reduce the mRNA and protein expressions of aging-related pl6INK4a.