Add-on aliskiren elicits stronger renoprotection than high-dose valsartan in type 2 diabetic KKAy mice that do not respond to low-dose valsartan.
Add-on aliskiren elicits stronger renoprotection than high-dose valsartan in type 2 diabetic KKAy mice that do not respond to low-dose valsartan.
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DOI：
10.1254/jphs.12031fp
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发表时间：
2012
影响因子：
3.5
通讯作者：
Nishiyama A
中科院分区：
文献类型：
--
作者：
Lei B;Nakano D;Fan YY;Kitada K;Hitomi H;Kobori H;Mori H;Masaki T;Nishiyama A
我们假设阿利吉仑对AT1受体拮抗剂治疗未获得足够肾保护作用的糖尿病动物具有肾脏保护作用。将12~16周龄的2型糖尿病KKAy小鼠随机分为两组，第1组：赋形剂，第2组：valsartan(15 mg/(kg·d))。随机分为4组，每组10只，分别给予药物治疗6周：1组继续给予赋形剂，2组给予15 mg/(kg·d)的valsartan(Val-VAL15)，3组给予valsartan(Val-Val50)50 mg/(kg·d)，4组给予valsartan 15 mg/(kg·d)+Aliskiren(Val-Val+ALI)25 mg/(kg·d)。阿利吉伦有显著的抗蛋白尿作用，而valsartan在前四周未能改善蛋白尿。令人惊讶的是，与赋形剂输注相比，Val-Val50组中Valsartan剂量的增加在减轻蛋白尿方面没有明显的趋势。Val-Val+ALI可明显抑制蛋白尿和足细胞损伤。Val-Val50和Val-Val+ALI对KKAy小鼠肾脏血管紧张素II含量的抑制作用相似。总之，在没有抗蛋白尿作用的2型糖尿病小鼠中观察到的抗蛋白尿作用可以归因于添加阿利吉伦。
We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by AT1-receptor antagonist treatment. Type 2 diabetic KKAy mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. The mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle, 2: group 2 continuously received 15 mg/kg per day of valsartan (Val-Val15), 3: group 2 received 50 mg/kg per day of valsartan (Val-Val50), 4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (Val-Val+Ali). Aliskiren exerted significant anti-albuminuric effects, whereas valsartan failed to ameliorate the albuminuria in the first four weeks. Surprisingly, the increasing dosage of valsartan in the Val-Val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. Val-Val+Ali significantly suppressed the development of albuminuria and podocyte injury. Val-Val50 and Val-Val+Ali showed similar suppression of angiotensin II contents in the kidney of KKAy mice. In conclusion, the anti-albuminuric effect that was observed in the type 2 diabetic mice showing no anti-albuminuric effect by valsartan can be attributed to the add-on aliskiren.
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影响因子：
13.6
作者：
Amsellem, Sabine;Gburek, Jakub;Kozyraki, Renata
通讯作者：
Kozyraki, Renata
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
6.1
作者：
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通讯作者：
Liu, Zhihong
影响因子：
158.5
作者：
Parving, Hans-Henrik;Persson, Frederik;Hollenberg, Norman K.
通讯作者：
Hollenberg, Norman K.
影响因子：
158.5
作者：
Haller, Hermann;Ito, Sadayoshi;Viberti, Giancarlo
通讯作者：
Viberti, Giancarlo