Candesartan early or late treatment reduced advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mice kidney
10.3760/cma.j.issn.1008-1372.2012.02.001
- VernacularTitle:坎地沙坦不同治疗时机对2型糖尿病KK/Ta小鼠肾脏晚期糖基化终末产物形成及其受体表达的影响
- Author:
Qiuling FAN
;
Xiaoming ZHAO
;
Shi PU
;
Sali LI
;
Gang YANG
;
Congxiao ZHANG
;
Yi JIANG
;
Lining WANG
- Publication Type:Journal Article
- Keywords:
Benzimidazoles/PD;
Tetrazoles/PD;
Diabetes mellitus,type 2/DT/ME;
Glycosylation end products,advanced
- From:
Journal of Chinese Physician
2012;14(2):145-150
- CountryChina
- Language:Chinese
-
Abstract:
Objective The effects of candesartan,an angiotensin Ⅱ type 1 receptor blocker (ARB) were investigated on advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mouse kidneys.MethodsKK/Ta mice(n=72)were random divided into three groups(n=24) and it was treated with candesartan [4 mg/(kg·d)] or vehicle from 6 or 12 to 28 weeks of age.BALB/c mice(n=24) treated with vehicle were used as controls.Body weight,blood pressure,blood glucose,urinary microalbumin,urinary creatinine and serum creatinine were measured every four weeks.At 28 weeks,renal expressions of carboxymethyllysine and RAGE were evaluated by immunohistochemistry and/or competitive RT-PCR.Results KK/Ta mice developed high body weight,high blood glucose,and high urinary microalbumin/creatinine ratio in KK/Ta mice at 28 weeks of age,and it was significantly higher than that of BALB/c mice [(427.49±89.37)mg/g vs (9.54±3.25)mg/g,P＜0.01 ].Protein and mRNA expressions of RAGE were upregulated in KK/Ta kidneys with increased immunostaining intensities of carboxymethyllysine.Candesartan treatment has markedly reduced urinary microalbumin/creatinine ratio [Early treatment group (32.18±9.41)mg/g,Late treatment group (53.20±7.26)mg/g,P＜0.01 ].Treatment with candesartan down-regulated the protein and mRNA expressions of RAGE and reduced the accumulation of carboxymethyllysine.There were no significant differences between the two treatment groups (from 6 or 12 weeks).ConclusionsThe results suggest that candesartan,an ARB,reduces advanced glycation end-products accumulation and subsequent albuminuria by down-regulating RAGE expression in type 2 diabetic KK/Ta mouse kidneys.
