Li Yan-Ju, Deng Lan, Huang Rui, Guo Kun-Yuan
Department of Hematology, Zhujiang Hospital, Nanfang Medical University, Guangzhou, China.
Zhonghua Nei Ke Za Zhi. 2009 Jun;48(6):458-61.
To study the effect of mesenchymal stem cells on the aging rat kidney and to explore the underlying mechanism.
Rat models of senile kidney were built with hypodermic injection of D-galactose daily. Injections of MSCs of 3 x 10(6) were given to each rat through vena caudalis and CFSE was used as a tracing label to detect the distribution of MSCs in vivo. After 24 h, rats were dissected and their kidneys were frozen for section. MSCs were observed with Fluophot and quantitative analysis of the various parameters of kidney was performed under a light microscope with BI2000 image analysis system. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and kidney were measured wtih hydroxylamine and chromatometry. The expression of VEGF and P16 mRNA in kidney tissue was detected with real-time PCR and Western blotting.
MSCs was found homing in the rat kidney, and the glomerular size, sclerosis-rate and the average cell count of glomerulus in the treated group were different from those of the model group (P < 0.05). In the treated group, the activity of SOD was significantly higher and the content of MDA was lower in serum and kidney than that in the model control group (P < 0.05). The expression of VEGF mRNA and protein in the kidneys of MSCs group increased significantly as compared with the model group (P < 0.05). The expression of P16 mRNA and protein in the kidney of MSCs group decreased significantly compared with the model group (P < 0.05).
MSCs can increase the expression of VEGF while decrease the expression of P16, so as to play a key role in the anti-aging on rat kidney.
研究间充质干细胞对衰老大鼠肾脏的作用并探讨其潜在机制。
通过每日皮下注射D-半乳糖建立老年肾脏大鼠模型。经尾静脉给每只大鼠注射3×10(6)的间充质干细胞,并使用羧基荧光素二醋酸盐琥珀酰亚胺酯(CFSE)作为追踪标记来检测间充质干细胞在体内的分布。24小时后,解剖大鼠并将其肾脏冷冻切片。用荧光光度计观察间充质干细胞,并使用BI2000图像分析系统在光学显微镜下对肾脏的各种参数进行定量分析。用羟胺法和比色法测定血清和肾脏中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量。用实时聚合酶链反应(PCR)和蛋白质免疫印迹法检测肾脏组织中血管内皮生长因子(VEGF)和P16 mRNA的表达。
发现间充质干细胞归巢于大鼠肾脏,治疗组的肾小球大小、硬化率和肾小球平均细胞数与模型组不同(P<0.05)。治疗组血清和肾脏中SOD的活性明显高于模型对照组,MDA的含量低于模型对照组(P<0.05)。与模型组相比,间充质干细胞组肾脏中VEGF mRNA和蛋白的表达明显增加(P<0.05)。与模型组相比,间充质干细胞组肾脏中P16 mRNA和蛋白的表达明显降低(P<0.05)。
间充质干细胞可增加VEGF的表达,同时降低P16的表达,从而在大鼠肾脏抗衰老中起关键作用。