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- 2018
人脐带间充质干细胞延缓大鼠肾脏衰老的作用
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Abstract:
摘要 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.
| [1] | de ALMEIDA D C, DONIZETTI-OLIVEIRA C, BARBOSA-COSTA P, et al. In Search of Mechanisms Associated with Mesenchymal Stem Cell-Based Therapies for Acute Kidney Injury[J]. The Clinical biochemist Reviews / Australian Association of Clinical Biochemists, 2013, 34(3): 131-144. |
| [2] | HAN Y S, LEE J H, JUNG J S, et al.Fucoidan protects mesenchymal stem cells against oxidative stress and enhances vascular regeneration in a murine hindlimb ischemia model[J]. Int J Cardiol, 2015,198(12):187-195. |
| [3] | MELK A, KITTIKOWIT W, SANDHU I, et al.Cell senescence in rat kidneys in vivo increases with growth and age despite lack of telomere shortening[J]. Kidney international, 2003, 63(6): 2134-2143. |
| [4] | YABUKI A, YONESHIGE S, TANAKA S, et al.Age-related histological changes in kidneys of Brown Norway rat[J]. The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 2014, 76(2): 277-280. |
| [5] | ZINDY F, QUELLE D E, ROUSSEL M F, et al.Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging[J]. Oncogene, 1997, 15(2): 203-211. |
| [6] | IRIE J, ITOH H.Aging and homeostasis. Age-associated diseases and clinical application of NMN(Nicotinamide Mononucleotide)[J]. Clin Calcium, 2017,27(7):983-990. |
| [7] | PISTOIA V, RAFFAGHELLO L.Mesenchymal stromal cells and autoimmunity[J]. Int Immunol, 2017,29(2):49-58. |
| [8] | FRISARD M, RAVUSSIN E.Energy metabolism and oxidative stress: impact on the metabolic syndrome and the aging process[J]. Endocrine, 2006, 29(1): 27-32. |
| [9] | TAKAHASHI K, OKUMURA H, GUO R, et al.Effect of oxidative stress on cardiovascular system in response to gravity[J]. Int J Mol Sci, 2017,18(7):E1426. |
| [10] | LIU Z, HU G D, LUO X B, et al.Potential of bone marrow mesenchymal stem cells in rejuvenation of the aged skin of rats[J]. Biomed Rep, 2017,6(3):279-284. |
| [11] | 周艳华, 许婷婷, 李军, 等. 人脐带间充质干细胞低氧条件培养液对小鼠造血系统自然衰老的影响[J]. 中国病理生理杂志, 2011, 27(3): 469-474. |
| [12] | ZHOU Y H, XU T T, LI J, et al.Effects of hypoxic-conditioned medium of mesenchymal stem cells form human umbilical cord on natural senescence of mouse hematopoietic system[J]. Chinese Journal of pathophysiology, 2011, 27(3):469-474. |
| [13] | 王福龙, 王甄真, 陈雁. 衰老的分子机制与干预研究的最新进展[J]. 中国细胞生物学学报, 2012, 34(8): 739-748. |
| [14] | WANG F L, WANG Z Z, CHEN Y.The molecular mechanism of aging and recent progress in intervention research[J]. Chinese Journal of Cell Biology, 2012, 34(8): 739-748. |
| [15] | UZUN D, KORKMAZ G G, SITAR M E, et al.Oxidative damage parameters in renal tissues of aged and young rats based on gender[J]. Clinical interventions in aging, 2013, 8(6): 809-815. |
| [16] | EL-TANTAWY W H, HALEEM E N. Therapeutic effects of stem cell on hyperglycemia, hyperlipidemia, and oxidative stress in alloxan-treated rats[J]. Molecular and cellular biochemistry, 2014, 391(1/2):193-200. |
| [17] | MELK A, KITTIKOWIT W, SANDHU I, et al.Cell senescence in rat kidneys in vivo increases with growth and age despite lack of telomere shortening[J]. Kidney international, 2003, 63(6): 2134-2143. |
