摘要
目的探讨Irisin在运动改善2型糖尿病大鼠肾功能中的作用及其可能机制。方法采用随机数表法从40只4~6周龄的雄性SD大鼠中,选取8只作为正常对照组(NC组),剩余大鼠用于构建2型糖尿病疾病模型。将造模成功后的大鼠再次按照随机数表法分为糖尿病模型组(DM组)、糖尿病运动组(DE组)、糖尿病Irisin组(DI组),8只/组。DE组进行8周的跑台运动干预,DI组进行8周的外源性Irisin注射干预。干预结束后取材,试剂盒检测相关生化指标;HE、Masson、PAS染色观察肾脏组织病理学形态;采用Westernblotting检测大鼠肾脏相关蛋白表达水平。结果与NC组相比,DM组大鼠空腹胰岛素、总胆固醇、甘油三酯、血肌酐、尿素氮含量升高(P<0.05),血清Irisin含量降低(P<0.05);与DM组相比,DE组与DI组总胆固醇、甘油三酯、血肌酐、尿素氮含量均下降(P<0.05),血清Irisin含量增加(P<0.05)。与NC组相比,DM组大鼠肾脏结构紊乱,胶原纤维沉积严重;而DE组与DI组肾脏结构较DM组大鼠均有不同程度的改善,胶原纤维沉积减少。与NC组相比,DM组大鼠肾脏组织FNDC5、LC3-Ⅱ/Ⅰ、Atg7、Beclin-1、p-AMPK、AMPK、SIRT1蛋白表达水平下降(P<0.05),p62蛋白表达升高(P<0.05)。与DM组相比,DE组与DI组大鼠肾组织FNDC5、LC3-Ⅱ/Ⅰ、Atg7、Beclin-1、p-AMPK、AMPK、SIRT1蛋白表达水平升高(P<0.05),p62蛋白表达下降(P<0.05)。结论运动与外源性Irisin两种方式均对2型糖尿病大鼠的肾脏起到保护作用,其机制可能与Irisin激活肾脏组织中AMPK/SIRT1通路,进而促进肾脏自噬有关。
Objective To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats.Methods Forty male SD rats aged 4-6 weeks were randomized into normal control group,type 2 diabetes mellitus model group,diabetic exercise(DE)group and diabetic irisin(DI)group(n=8).The rats in DE group were trained with treadmill running for 8 weeks,and those in DI group were given scheduled irisin injections for 8 weeks.After the treatments,blood biochemical parameters of the rats were examined,and renal histopathology was observed with HE,Masson and PAS staining.Western blotting was used to detect the protein expression levels in the rats'kidneys.Results The diabetic rats showed significantly increased levels of fasting insulin,total cholesterol,triglyceride,serum creatinine and blood urea nitrogen with lowered serum irisin level(all P<0.05).Compared with those in DM group,total cholesterol,triglyceride,serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups(all P<0.05).The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys,which were significantly improved in DE group and DI group.Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5,LC3-II/I,Atg7,Beclin-1,p-AMPK,AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats(all P<0.05).Conclusion Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.
作者
周凤敏
郭艳菊
陈宁
ZHOU Fengmin;GUO Yanju;CHEN Ning(College of Sport Medicine,Wuhan Sports University,Wuhan 430079,China;Hubei Key Laboratory for Exercise Training and Monitoring,Wuhan Sports University,Wuhan 430079,China;College of Physical Education and Health,Guangxi Normal University,Guilin 541006,China;Department of Rehabilitation,Jiangsu Rongjun Hospital,Wuxi 214000,China)
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2024年第4期675-681,共7页
Journal of Southern Medical University
基金
国家自然科学基金(31771318)
广西教育厅科研资助项目(2021KY0066)。
