当前位置:
首页
网刊
缬沙坦对糖尿病肾病大鼠足细胞自噬的影响
缬沙坦对糖尿病肾病大鼠足细胞自噬的影响
王晓丹1,2,高丽辉1,牛艳芬1,林 华1,王晋文2,李 玲1

1 昆明医科大学生物医学工程研究中心,昆明 650500;2 昆明医科大学附属延安医院,昆明 650051
Effects of valsartan on podocyte autophagy in rats with diabetic nephropathy
(1 Biomedical Engineering Research Center, Kunming Medical University,Kunming 650500,China;2 Yanan Hospital Affiliated to Kunming Medical University, Kunming 650051,China)

摘要参考文献相关文章

起始页:174

摘要:[摘要] 目的:研究缬沙坦对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病(diabetic nephropathy,DN)大鼠的改善作用,及对大鼠足细胞自噬的影响。方法:雄性SD大鼠30只,随机分正常组、模型组和缬沙坦组(n=10)。腹腔注射STZ复制糖尿病动物模型,成模后每日灌胃(ig)给予缬沙坦20 mg?kg-1,12周后检测24 h尿蛋白定量、空腹血糖、血肌酐和尿素氮。PAS染色观察肾小球病理改变,免疫荧光双染观察Nephrin及LC3共染色情况。Western Blot检测Nephrin,LC3和p62蛋白的表达。结果:与模型组相比,缬沙坦组大鼠24 h尿蛋白减少,Nephrin和LC3-Ⅱ蛋白表达上调,p62蛋白表达下调(P<0.05)。结论:缬沙坦可能通过提高自噬水平保护足细胞,降低蛋白尿,从而延缓DN进展。

关键词:[关键词] 缬沙坦;自噬;足细胞;糖尿病肾病

通讯作者:

基金项目:

作者简介:

Abstract:[Abstract] Objective:To study the effects of valsartan on kidney and podocytes autophagy in rats with diabetic nephropathy(DN). Methods: A total of 30 SD rats were randomly divided into 3 groups,that is,normal group,diabetic group,and valsartan group (n=10). Diabetic animal were induced by an intraperitoneal injection of STZ.Diabetic rats were given valsartan 20 mg?kg-1 by oral gavage once daily for 12 weeks.At the end of experiment, serum glucose, creatinine and urea nitrogen were measured. 24-hour urinary specimens were collected for determining albumin. The kidneys were taken out and renal pathological changes were observed after PAS staining. LC3 and P62 protein, as autophagy markers, as well as nephrin were detected by Western blotting. Immunofluorescence double dye of nephrin and LC3 was used to detect the autophagy of podocytes. Results: Compared with the diabetic model group,valsartan ameliorated glomerular pathological changes, raised the protein expression of nephrin and LC3-Ⅱ, and decreased the expression of P62 (P<0.05). Conclusion:Valsartan has protective effect on the kidney of DN rats, which may be related to its effect of promoting podocyte autophagy.

Key words:[Key words] valsartan; autophagy; podocytes; diabetic nephropathy

    [1] PAGTALUNAN ME, MILLER PL, JUMPING-EAGLE S, et al.Podocyte loss and progressive glomerular injury in type II diabetes[J]. J Clin Invest,1997, 99(2):342-348.
    [2] TAGAWA A, YASUDA M, KUME S, et al. Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy[J]. Diabetes,2016,65(3):755-767.
    [3] WANG W, QIU L, HOWARD A, et al. Protective effects of aliskiren and valsartan in mice with diabetic nephropathy[J]. J Renin Angiotensin Aldosterone Syst,2014,15(4):384-395. 
    [4] ZHOU G, CHEUNG AK, LIU X, et al. Valsartan slows the progression of diabetic nephropathy in db/db mice via a reduction in podocyte injury, and renal oxidative stress and inflammation[J]. ClinSci (Lond),2014,126(10):707-720.
    [5] GAO Q, SHEN W, QIN W, et al. Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy[J]. Nephrol Dial Transplant,2010,25(11):3539-3547.
    [6] ZHANG Y, CHEN B, HOU XH, et al. Effects of mycophenolatemofetil, valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats[J]. Chin Med J (Engl),2007,120(11):988-995.


    [7] 包自阳,朱彩凤,李建秋,等. 缬沙坦对IgA肾病大鼠血清IgA1异常糖基化的影响

    [J]. 中国现代应用药学,2014 ,31(3):274-278.


    [8] 寸玉芳,杨四涛,席宇飞,等. 1例瑞舒伐他汀联用缬沙坦致梗阻性黄疸的药学监护

    [J]. 中国现代应用药学, 2015,32(5):640-642.
    [9] HARTLEBEN B, GDEL M, MEYER-SCHWESINGER C, et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice[J]. J Clin Invest,2010,120(4): 1084-1096. 
    [10] LANGHAM RG, KELLY DJ, COX AJ,et al. Proteinuria and the expression of the podocyteslit diaphragm protein, nephrin, in diabetic nephropathy:effects of angiotensin converting enzyme inhibition[J].Diabetologia,2002, 45(11): 1572-1576.
    [11] KOOP K, EIKMANS M, BAELDE HJ, et al. Expression of podocyte-associated molecules in acquired human kidney diseases[J]. J Am Soc Nephrol, 2003, 14(8): 2063-2071.
    [12] DOUBLIER S, SALVIDIO G, LUPIA E,et al. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II[J]. Diabetes, 2003, 52(4): 1023-1030.
    [13] KOMATSU M, WAGURI S, KOIKE M, et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice[J]. Cell, 2007,131(6):1149-1163.