甜菜碱对糖尿病肾病小鼠的治疗作用及其机制

目的探讨分子伴侣甜菜碱(betaine)对糖尿病肾病小鼠的治疗作用及机制。方法 db/db小鼠按随机数字表法分为糖尿病肾病(diabetic nephropathy,DN)组和甜菜碱治疗组(DN+B),db/m小鼠作为正常对照组,每组18只。在治疗第4、8、12周末分别采用实时荧光定量PCR和Western blot技术测定GRP78的表达水平,ELISA测定尿单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)的含量,常规病理和生化方法检测肾脏病理、血糖(blood glucose,BG)、血肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)、24 h尿蛋白排泄率(urinary albumin excretion rate,UAER)的动态改变。结果①与同期正常对照组比较,DN组小鼠的BG、BUN、24 h UAER、MCP-1均明显升高(P<0.05),甜菜碱治疗后可明显降低BG、BUN、24 h UAER、MCP-1水平(P<0.05),而对Scr无明显影响。②与正常对照组比较,12周时DN组小鼠肾小球基底膜增厚,系膜细胞增生,系膜基质积聚,而甜菜碱治疗后可明显抑制肾脏的病理变化。③与正常对照组比较,DN组小鼠肾脏组织GRP78 mRNA和蛋白质表达水平均显著升高(P<0.05),甜菜碱治疗后可明显抑制GRP78的表达(P<0.05)。结论甜菜碱可能通过减轻内质网应激(endoplasmic reticulum stress,ERS)及相关的炎症反应治疗DN小鼠。

Therapeutic effect of betaine on diabetic nephropathy in db/db mice

Objective To study the effect of betaine on diabetic nephropathy(DN) in mice.Methods Thirty-six db/db mice were randomly divided into DN group(n=18) and betaine treatment group(n=18),with 18 db/m mice served as a normal control group(NC group).At the end of 4,8 and 12 weeks,GRP78 expression level in the renal tissue was measured by real-time quantitative fluorescence PCR and Western blotting,urine monocyte chemoattractant protein-1(MCP-1) concentration was assayed by ELISA,and dynamic renal pathology,blood glucose(BG),serum creatinine(SCr),blood urea nitrogen(BUN),24-hour urinary albumin excretion rate(UAER) were tested with routine pathological and biochemical methods.Results The BG,BUN,24-h UAER and MCP-1 levels were significantly higher in DN group than in NC group(P<0.05),which became significantly lower after betaine treatment.However,betaine had no effect on Scr.The glomerular basement membrane was thicker,the number of mesangial cells was greater,and more mesangial matrix was accumulated in DN group than in NC group at 12 weeks(P<0.05),which were significantly alleviated after betaine treatment.The GRP78 mRNA and protein expression levels were significantly higher in DN group than in NC group(P<0.05),which became significantly lower after betaine treatment(P<0.05).Conclusion Betaine can exert its effect on DN in db/db mice by alleviating endoplasmic reticulum stress(ERS) and related inflammatory reactions.