N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对糖尿病肾病小鼠肾组织的保护作用及机制  

Protective role of N-acetyl-seryl-aspartyl-lysyl-proline in renal tissue of mice with diabetic nephropathy and possible mechanisms

作　　者：查冬青[1] 吴小燕[1] 

机构地区：[1]武汉大学中南医院肾内科,武汉430071

出　　处：《临床肾脏病杂志》2017年第12期757-760,共4页Journal Of Clinical Nephrology

基　　金：国家自然科学基金青年项目(No.81400694;No.81170679)

摘　　要：目的通过对糖尿病肾病小鼠模型的研究,探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(N-acetyl-seryl-aspartyl-lysyl-proline,AcSDKP)对糖尿病肾病小鼠肾组织的保护作用及可能机制。方法将18只小鼠随机分为正常组(n=6)、模型组(n=12)。通过一次性腹腔注射链脲佐菌素(streptocozin,STZ)建立糖尿病小鼠模型,糖尿病模型建立成功后再分为糖尿病组(n=6)、糖尿病+AcSDKP组(n=6)。糖尿病+AcSDKP组小鼠予AcSDKP口服(1 mg·kg^(-1)·2 d^(-1),溶于饮用水瓶中),糖尿病组予常规饮用水。12周后测量小鼠血压、心率、血糖,收集小鼠血、尿标本用于检测生化指标及尿白蛋白/肌酐比值。处死大鼠后留取肾组织标本,通过普通光镜和电镜观察肾脏形态学及超微结构改变。采用免疫荧光法检测肾组织中足细胞蛋白(nephrin)的表达改变,采用免疫印迹法检测肾组织纤连蛋白(fibronectin)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达改变。结果(1)与对照组相比,糖尿病小鼠出现血糖明显升高,建模成功后12周出现明显白蛋白尿,足细胞出现足突融合、增宽,肾脏出现纤维化,肾小球表面面积及系膜区面积明显增加,肾小球nephrin表达明显减少,而糖尿病小鼠血压无明显改变。(2)AcSDKP可减少糖尿病小鼠蛋白尿,减轻足细胞足突融合及增宽,缓解肾小球肥大及系膜增殖,改善肾脏纤维化。(3)AcSDKP可减少肾组织fibronectin、α-SMA的表达,部分恢复肾脏nephrin的表达。结论 AcSDKP可减轻糖尿病小鼠肾组织病变,其保护作用与减轻足细胞nephrin表达有关,为糖尿病肾病提供新的治疗手段及理论依据。Objective To investigate the role and possible mechanisms of N-acetyl-seryl-aspartyl-lysyl-proline（AcSDKP）in renal tissue of mice with diabetic nephropathy（DN）.Methods The mice were randomly divided into control,diabetic mellitus（DM）,and DM treated with AcSDKP（DM＋AcSDKP）groups.The DM model was established by a single intraperitoneal injection of streptozotocin.Natrium citricumbuffer solution of same volume was intraperitoneally injected in the control group.The DM rats in AcSDKP group were orally administrated with AcSDKP（1 mg/kg every two days）for 12 weeks.Blood and urine samples were collected before mice were sacrificed 12 weeks later.The glomerular morphology and podocyte ultrastructure were observed under the light and transmission election microscopies respectively.The expression of nephrin was detected by immunofluorescence.Western blotting was used to detect the expression of fibronectin andα-SMA proteins in the renal tissues.Results（1）Albuminuria was increased 12 weeks after streptozotocin injection.DM mice displayed foot process fusion and broadening,renal fibrosis and increased glomerular surface area.The expression of nephrin was decreased in DM group.Blood pressure had no significant change in three groups.（2）AcSDKP decreased albuminuria,alleviated foot process fusion,ameliorated glomerularhypertrophy and renal fibrosis in DM mice.（3）AcSDKP decreased the expression of renal fibronectin andα-SMA,and restored the expression of nephrin in DM mice.Conclusions AcSDKP alleviated the progression of DN via protecting against renal podocyte impairment.

关 键 词：N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 糖尿病肾病 足细胞 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]