甜菜碱对糖尿病肾病小鼠的治疗作用及机制 .doc

甜菜碱对糖尿病肾病小鼠的治疗作用及其机制 陈吉刚，庞 琦，曾 薇，郭艳红，牟 娇，聂 凌，袁发焕，冯 兵（400037 重庆，第三军医大学新桥医院肾内科） [基金项目] 国家自然科学基金 [通信作者] 冯 兵， E-mail：fxb12@ [摘要] 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，DN18只。在治疗第4、8、12(blood glucose，BG)(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与同期组比较，DN组小鼠的BG、BUN、24 h UAER、MCP-1均明显升高（P0.05），甜菜碱治疗后可明显降低BG、BUN、24 h UAER、MCP-1水平（P0.05），而对Scr无明显影响。②与组比较，12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，而甜菜碱治疗可明显抑制肾脏的病理变化。③与组比较，DN组小鼠肾脏组织GRP78 mRNA和蛋白质表达水平均显著升高（P0.05），甜菜碱可明显抑制GRP78的表达。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。R587.2 [文献标志码] A Effect of betaine on diabetic nephropathy in db/dh mice and its mechanism Chen Jigang, Pang Qi, Zeng Wei, Guo Yanhong, Mu Jiao, Nie Ling, Yuan Fahuan, Feng Bing（Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China） [Abstract] Objective To study the effect of betaine on diabetic nephropathy (DN)in mice and its mechanism. Methods Thirty-four 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 was measured by RT- PCR, 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-1C levels were significantly higher in DN group than in NC group (P0.05), 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