烟酰胺单核苷酸通过TGFβ/Smad3信号通路减轻Alport综合征小鼠肾纤维化  

Nicotinamide mononucleotide attenuates renal fibrosis in mice with Alport syndrome through TGFβ/Smad3 signaling pathway

作　　者：李沫 王星星 黎上明 李晓梅 张秀芬 韩晓 杨细飞 LI Mo;WANG Xingxing;LI Shangming;LI Xiaomei;ZHANG Xiufen;HAN Xiao;YANG Xifei(School of Public Health,Shanxi Medical University,Taiyuan 030000,China;Shenzhen Key Laboratory of Modern Toxicology,Shenzhen Medical Key Discipline of Health Toxicology,Shenzhen Center for Disease Control and Prevention,Shenzhen 518055,China;University of Macao,Macao 519000,China;College of Pharmacy,Jinan University,Guangzhou 510632,China;School of Public Health,University of Nanhua,Hengyang 421001,China)

机构地区：[1]山西医科大学公共卫生学院,山西太原030000 [2]深圳市疾病预防控制中心深圳市现代毒理学重点实验室,深圳市卫生毒理学医学重点学科,广东深圳518055 [3]澳门大学,澳门519000 [4]暨南大学药学院,广东广州510632 [5]南华大学公共卫生学院,湖南衡阳421001

出　　处：《中国病理生理杂志》2025年第3期518-523,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.82171583)的部分资助;深圳市科技创新委员会重点基础研究项目(No.JCYJ20200109150717745,No.JCYJ20200109144418639);深圳市医疗卫生三名工程项目(No.SZSM202211010);深圳市医学重点学科建设经费资助项目(No.SZXK069)。

摘　　要：目的:探讨烟酰胺单核苷酸(NMN)是否通过TGFβ/Smad3通路减轻Alport综合征(AS)小鼠肾脏纤维化。方法:选用SPF级雌性X连锁AS(COL4A5 KI)小鼠,分为模型组(AS组)和模型给药组(AS+NMN组);雌性C57BL/6小鼠作为野生型(WT)组,每组小鼠7~8只。给药组小鼠于8周龄时经口给药,给药8周,至16周龄;其余小鼠给予生理盐水灌胃。生化检测小鼠尿微量白蛋白/尿肌酐比值(UACR)。小鼠取材后,通过Masson染色分析肾纤维化情况;免疫组化检测纤维化相关分子肌间线蛋白(desmin)和α-平滑肌肌动蛋白(α-SMA)的表达水平;用蛋白免疫印迹检测纤维化相关蛋白desmin、α-SMA、转化生长因子β(TGFβ)、Smad3、p-Smad3和纤连蛋白(fibronectin)的表达。结果:与模型组相比,NMN治疗后,AS小鼠UACR显著降低(13周,P<0.01;15周,P<0.01),纤维化相关蛋白表达降低(P<0.05)。结论:NMN通过TGFβ/Smad3信号通路能减轻AS小鼠肾脏纤维化。AIM:To study the effect of nicotinamide mononucleotide(NMN)on renal fibrosis in mice with Al-port syndrome(AS)through TGFβ/Smad3 pathway.METHODS:SPF grade female X-linked AS(COL4A5 KI)mice were divided into model group(AS group)and model drug administration group(AS+NMN group).while female C57BL/6 mice served as the wild-type(WT)group,with 7 to 8 mice in each group.The mice in the administration group were given oral administration at 8 weeks of age for 8 weeks to 16 weeks of age.The remaining mice were given saline intragastric ad-ministration.The ratio of urinary microalbumin to urinary creatinine(UACR)was measured by biochemical method.After sampling,the renal fibrosis was analyzed by Masson staining.The expression levels of desmin andα-smooth muscle actin(α-SMA)were detected by immunohistochemistry.The expressions of fibrosis-related proteins desmin,α-SMA,trans-forming growth factorβ(TGFβ),Smad3,p-Smad3,and fibronectin were detected by Western blot.RESULTS:Com-pared with the model group,UACR(13 weeks,P<0.01;15 weeks,P<0.01)and fibrosis-related protein expression(P<0.05)in AS mice were significantly decreased after NMN treatment.CONCLUSION:Treatment with NMN attenuates renal fibrosis in AS mice through TGFβ/Smad3 signaling pathway.

关 键 词：烟酰胺单核苷酸 ALPORT综合征 肾纤维化 TGFβ/Smad3信号通路 

分 类 号：R692.2[医药卫生—泌尿科学] R363[医药卫生—外科学] R965[医药卫生—临床医学]