摘要
[目的]基于沉默信息调节因子1(Sirt1)/过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α)通路探讨豆甾醇对糖尿病肾病(DKD)大鼠足细胞自噬的影响。[方法]通过高糖和高脂、链脲佐菌素溶液建立DKD大鼠,并随机分为DKD组、不同剂量的豆甾醇(豆甾醇-低50 mg/kg、豆甾醇-高200 mg/kg)组、缬沙坦(8.33 mg/kg)组、豆甾醇-高+EX527(5 mg/kg)组,并以普通饲料喂养的大鼠为正常组;结束后,检测尿蛋白含量及血糖;试剂盒检测尿素氮(BUN)、血肌酐(Scr)水平;分离肾组织,评估组织病理学及足细胞结构、自噬小体变化;检测肾组织中足细胞裂孔隔膜蛋白分子(Nephrin、Podocin)阳性表达、自噬标志蛋白(Beclin-1、P62)mRNA表达及沉默信息调节因子1(Sirt1)/过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)通路相关蛋白表达。[结果]DKD组Nephrin、Podocin阳性表达、Beclin-1 mRNA、Sirt1、PGC-1α蛋白表达低于正常组,血糖、尿蛋白、Scr、BUN、P62 mRNA表达增加(P<0.05);豆甾醇-低组、豆甾醇-高组、缬沙坦组Nephrin、Podocin阳性表达、Beclin-1 mRNA、Sirt1、PGC-1α蛋白表达高于DKD组,血糖、尿蛋白、Scr、BUN、P62 mRNA表达降低(P<0.05);豆甾醇-高+EX527组Nephrin、Podocin阳性表达、Beclin-1 mRNA、Sirt1、PGC-1α蛋白表达低于豆甾醇-高组,血糖、尿蛋白、Scr、BUN、P62 mRNA表达增加(P<0.05)。[结论]豆甾醇通过激活Sirt1/PGC-1α通路提高DKD大鼠足细胞自噬,减轻足细胞损伤。
[Objective]To discuss the effect of stigmasterol on autophagy of podocytes in diabetic kidney disease(DKD)rats based on the silent information regulator 1(Sirt1)/peroxisome proliferator⁃activated receptorγcoactivator 1α(PGC⁃1α)pathway.[Methods]DKD rats were established using high⁃glucose and high⁃fat,streptozotocin solution,and stochastically separated into the DKD group,different doses of stigmasterol(stigmasterol⁃low50 mg/kg,stigmasterol⁃high 200 mg/kg)groups,valsartan(8.33 mg/kg)group,and stigmasterol⁃high+EX527(5 mg/kg)group.And the rats fed with ordinary feed were regarded as the normal group.The urine protein content and blood glucose were detected.The levels of blood urea nitrogen(BUN)and serum creatinine(Scr)were detected by the kits.Renal tissues were isolated to evaluate histopathology and changes in podocyte structure and autophagosomes.The positive expressions of podocular pore membrane protein molecules(Nephrin,Podocin),the expressions of autophagy marker proteins(Beclin⁃1,P62)mRNA,and the expressions of Sirt1/PGC⁃1αpathway⁃related proteins in renal tissue were detected.[Results]The DKD group had lower positive expressions of Nephrin and Podocin,and the expressions of Beclin⁃1 mRNA,Sirt1,and PGC⁃1αproteins,and higher blood glucose,urine protein,Scr,BUN,and expression of P62 mRNA than the normal group(P<0.05).The stigmasterol⁃low group,stigmasterol⁃high group and valsartan group had higher positive expressions of Nephrin and Podocin,and the expressions of Beclin⁃1 mRNA,Sirt1,and PGC⁃1αproteins,and lower blood glucose,urine protein,Scr,BUN,and expression of P62 mRNA than the DKD group(P<0.05).The stigmasterol⁃high+EX527 group had lower positive expressions of Nephrin and Podocin,and the expressions of Beclin⁃1 mRNA,Sirt1,and PGC⁃1αproteins,and higher blood glucose,urine protein,Scr,BUN,and expression of P62 mRNA than the stigmasterol⁃high group(P<0.05).[Conclusion]Stigmasterol enhances autophagy of podocytes in DKD rats and alleviates podocyte injury by activating the Sirt1/PGC⁃1αpathway.
作者
胡冬怡
谷东风
刘变玲
赵继芳
沈蓓莉
吴梦
HU Dongyi;GU Dongfeng;LIU Bianling;ZHAO Jifang;SHEN Beili;WU Meng(Department of Nephrology,The Fifth Clinical College of Henan University of Chinese Medicine(People’s Hospital of Zhengzhou),Zhengzhou 450000,China)
出处
《天津中医药》
2026年第4期485-490,共6页
Tianjin Journal of Traditional Chinese Medicine
基金
河南省医学科技攻关计划项目(LHGJ20240889)
郑州市医疗卫生领域科技创新指导计划项目(2024YLZDJH279)。
