脂联素受体激动剂通过激活SIRT1信号通路延缓D-半乳糖诱导小鼠肾脏衰老  

AdipoRon delays renal aging induced by D-gal in mice via activating the SIRT1 signaling pathway

作　　者：张宗敏 梁婧 黄山 何国丽 沈沛 周满红 Zhang Zongmin;Liang Jing;Huang Shan;He Guoli;Shen Pei;Zhou Manhong(Department of Geriatrics,the Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China;Zunyi Medical University,Zunyi 563000,China;Department of Emergency,the Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China)

机构地区：[1]遵义医科大学附属医院老年医学科,遵义563000 [2]遵义医科大学,遵义563000 [3]遵义医科大学附属医院急诊科,遵义563000

出　　处：《中华老年医学杂志》2024年第12期1592-1598,共7页Chinese Journal of Geriatrics

基　　金：贵州省卫健委科技基金(gzwkj2021-045)。

摘　　要：目的探讨脂联素受体激动剂(AdipoRon)对D-半乳糖(D-gal)诱导的小鼠肾脏衰老的影响及其可能的机制。方法雄性C57BL/6J小鼠随机分为对照组、D-gal模型组、AdipoRon组,每组各10只。对照组给予生理盐水灌胃及皮下注射,D-gal组给予生理盐水灌胃及D-gal皮下注射,AdipoRon组给予AdipoRon溶液灌胃及D-gal皮下注射,连续8周。8周后,取小鼠血液及肾组织进行检测。苏木精-伊红(HE)染色、Masson染色及电镜观察肾组织病理学变化;全自动生化分析仪检测小鼠血肌酐(SCr)、尿素氮(BUN)及胱抑素-C(Cys-C)水平;免疫组织化学染色及蛋白免疫印迹法(Western blot)检测肾组织中P53、P21、P16INK4a、沉默信息调节因子2相关酶1(SIRT1)、核因子E2相关因子2(NRF2)、Klotho蛋白的表达情况。结果与对照组相比较,D-gal组小鼠肾小球分布稀疏,结构不规整,肾小球硬化,肾小囊腔扩大,肾小管萎缩,足突融合、变宽,肾间质可见大量蓝染的胶原纤维沉积;AdipoRon组小鼠肾脏病理损伤较D-gal组明显减轻。与对照组相比较,D-gal组小鼠SCr[(23.13±2.21)μmol/L]、BUN[(19.58±1.63)μmol/L]、Cys-C[(0.15±0.02)μmol/L]水平均增加;AdipoRon组SCr[(16.97±1.16)μmol/L]、BUN[(16.25±1.25)μmol/L]、Cys-C[(0.12±0.01)μmol/L]水平较D-gal组下降(F=66.61、40.37、48.77,均P<0.001)。与对照组相比较,D-gal组小鼠肾组织中衰老蛋白P53(1.68±0.11)、P21(2.40±0.45)、P16INK4a(1.89±0.16)蛋白表达量增多,抗衰老蛋白SIRT1(0.46±0.04)、NRF2(0.65±0.05)、Klotho(0.42±0.03)蛋白表达量减少;与D-gal组相比较,AdipoRon组小鼠肾组织衰老蛋白P53(1.27±0.06)、P21(1.84±0.35)、P16INK4a(1.10±0.14)表达量减少,抗衰老蛋白SIRT1(0.78±0.05)、NRF2(0.87±0.07)、Klotho(0.65±0.06)表达量增多(F=152.38、44.45、147.54、219.69、42.25、166.49,均P<0.001)。结论AdipoRon可能通过激活SIRT1信号通路来延缓D-gal诱导的小鼠肾脏衰老。ObjectiveTo investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.MethodsMale C57BL/6J mice were randomly divided into three groups:a control group,a D-gal model group,and an AdipoRon group,each consisting of ten mice.The control group received saline through gavage and subcutaneous injection,the D-gal group received saline through gavage and D-gal through subcutaneous injection,and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks,following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining,Masson staining,and electron microscopy.Levels of serum creatinine(SCr),urea nitrogen(BUN),and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53,P21,P16INK4a,Silent mating-type information regulation 2 homolog 1(SIRT1),Nuclear factor E2-related factor 2(NRF2),and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.ResultsThe glomeruli exhibited sparse and irregular structure,with sclerosis and dilated capsular space.Renal tubules showed atrophy,while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21μmol/L),BUN(19.58±1.63μmol/L),and Cys-C(0.15±0.02μmol/L)were higher in the D-gal group than in the control group.Conversely,SCr(16.97±1.16μmol/L),BUN(16.25±1.25μmol/L),and Cys-C(0.12±0.01μmol/L)levels in the AdipoRon group were lower than those in the D-gal group(F=66.61,40.37,48.77,all P<0.001).The expression levels of aging proteins like P53(1.68±0.11),P21(2.40±0.45),and P16INK4a(1.89�

关 键 词：脂联素受体激动剂 D-半乳糖 肾脏衰老 SIRT1信号通路 

分 类 号：R692[医药卫生—泌尿科学]