Additive antifibrotic effects of pioglitazone and candesartan on experimental renal fibrosis in mice
Additive antifibrotic effects of pioglitazone and candesartan on experimental renal fibrosis in mice
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DOI：
10.1111/j.1440-1797.2009.01253.x
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发表时间：
2010-04-01
期刊：
影响因子：
2.5
通讯作者：
Kumagai, Hiroo
中科院分区：
文献类型：
--
作者：
Higashi, Keishi;Oda, Takashi;Kumagai, Hiroo
目的：探讨过氧化物酶体增殖物激活受体γ激动剂吡格列酮（Pio）和血管紧张素II受体阻断剂坎地沙坦（Cand）对单侧输尿管梗阻（UUO）小鼠肾纤维化模型的保护作用。方法：将UUO小鼠随机分为4组，分别腹腔注射Pio（10 mg/kg/day）、Cand（1 mg/kg/day）、Cand + Pio或溶媒10 d。生理参数，肾纤维化的程度和相关分子进行了分析，假手术小鼠作为controls.Results：总胶原含量测定显示突出的肾脏纤维化的车辆治疗的小鼠，显着减弱的Cand-treated和Pio-treated小鼠的肾纤维化，并进一步减弱肾纤维化的（Cand + Pio）-treated小鼠。实时定量逆转录聚合酶链反应（RT-PCR）结果显示，肾组织中TGF-β、胶原蛋白I和III以及纤溶酶原激活物抑制剂-1的mRNA表达也明显减弱。结论：吡格列酮和坎地沙坦对UUO小鼠肾纤维化具有相加的保护作用，联合应用可能是治疗慢性肾脏病的有效方法。
Aim:To examine the additive protective effects of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone (Pio) and the angiotensin II receptor blocker candesartan (Cand) in a murine model of renal fibrosis: mice with unilateral ureteral obstruction (UUO).Methods:Mice were randomly assigned into four groups that after UUO received i.p. injections of either Pio (10 mg/kg/day), Cand (1 mg/kg/day), Cand + Pio or vehicle for 10 days. Physiological parameters, the degree of renal fibrosis and molecules related to renal fibrosis were analysed, and sham-operated mice were used as controls.Results:Total collagen assay showed prominent renal fibrosis in the vehicle-treated mice, significantly attenuated renal fibrosis in the Cand-treated and the Pio-treated mice, and further attenuated renal fibrosis in the (Cand + Pio)-treated mice. Real-time reverse transcription polymerase chain reaction revealed that this attenuation pattern was also evident in the expression of the mRNA for transforming growth factor-beta, collagens I and III, and plasminogen activator inhibitor-1.Conclusion:Pioglitazone and candesartan have additive protective effects on renal fibrosis due to UUO in mice, suggesting that their use in combination would be an effective treatment for chronic kidney disease.