中国临床药理学与治疗学2012，Vol.17Issue(6)：627-633,7.
坎地沙坦不同治疗时机对2型糖尿病KK/Ta小鼠肾脏血管紧张素1型和2型受体表达的影响
Effects of candesartan early or late treatment on angiotensin Ⅱ type 1 and type 2 receptor expression in type 2 diabetic KK/Ta mice kidney
摘要
Abstract
AIM: To investigate the effects of candesartan, an angiotensin II type 1 receptor blocker (ARB) on angiotensin II type 1 (ATI) and type 2 (AT2) receptor expression in type 2 diabetic KK/Ta mouse kidneys. METHODS. KK/Ta mice divided into three groups were treated with candesartan (4 mg · kg-1 · d-1) or vehicle from 6 or 12 to 28 weeks of age. BALB/c mice(n = 6) 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, morphometric analysis including the whole glomerular area (WGA), glo-merular tuft area (GTA), extracellular matrix area (ECMA) and intraglomerular cell nuclei number (NIGCN) was conducted, and renal expressions of ATI and AT2 were evaluated by immunohistochemistry and immunofluorescence. RESULTS: KK/Ta mice developed higher body weight, blood glucose, and urinary microalbu-min/creatinine ratio in KK/Ta mice at 28 weeks of age were significantly higher than that of BALB/c mice (427. 49±89. 37 mg/g vs. 9. 54± 3.25 mg/g,P<0. 01). ATI expression was up- regulated, and AT2 expression was downregu-lated in KK/Ta kidneys with increased WGA, GTA, ECMA and NIGCN. 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 inhibited ATI expression and increased AT2 expression. Candesartan treatment reduced WGA, GTA, ECMA, NIGCN, and mean blood pressure. There were no significant differences between the two treatment groups (from 6 or 12 weeks). CONCLUSION- The results suggest that candesartan, an ARB, attenuated glomerular hypertrophy and mesangial matrix accumulation and subsequent albuminuria by down-regulating ATI expression and up-regulating AT2 expression in type 2 diabetic KK/Ta mouse kidneys.关键词
糖尿病肾病/坎地沙坦/KK/Ta小鼠/血管紧张素1型受体/血管紧张素2型受体Key words
Diabetic nephropathy/ Candesartan/ KK/Ta mice/Angiotensin II type 1 receptor/ Angiotensin II type 2 receptor分类
医药卫生引用本文复制引用
范秋灵,肇晓明,蒲实,李卅立,杨刚,姜奕,王力宁..坎地沙坦不同治疗时机对2型糖尿病KK/Ta小鼠肾脏血管紧张素1型和2型受体表达的影响[J].中国临床药理学与治疗学,2012,17(6):627-633,7.基金项目
国家自然科学基金资助项目(30700369) （30700369）
教育部留学回国人员科研启动基金资助项目(教外司留[2006]331号) （教外司留[2006]331号）
辽宁省教育厅高校科研计划项目(L2010658) （L2010658）
沈阳市科技计划项目(F11-264-1-38) （F11-264-1-38）
