Contribution of chymase-dependent angiotensin II formation to the progression of tubulointerstitial fibrosis in obstructed kidneys in hamsters.
Contribution of chymase-dependent angiotensin II formation to the progression of tubulointerstitial fibrosis in obstructed kidneys in hamsters.
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DOI：
10.1254/jphs.09152fp
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发表时间：
2009-09
影响因子：
3.5
通讯作者：
Kohno M
中科院分区：
文献类型：
--
作者：
Fan YY;Nishiyama A;Fujisawa Y;Kobori H;Nakano D;Matsuura J;Hase N;Hitomi H;Kiyomoto H;Urata H;Kohno M
最近的研究表明，酶在调节血管紧张素II （AngII）在心血管和肾组织的形成中的作用。我们研究了乳糜酶在单侧输尿管梗阻（UUO）中对AngII形成和肾纤维化的可能贡献。8周大的叙利亚仓鼠接受UUO治疗，并分别用载药、特异性溶酶抑制剂（CI） 4-[1-（4-甲基苯并[b]噻吩-3-甲基）- 1h -苯并咪唑-2-基磺酰]-丁酸（50 mg/kg，每天2次，p.o）或选择性at1受体阻滞剂奥美沙坦（10 mg/kg，每天，p.o,）治疗14天。uuo诱导的肾间质纤维化与肾脏α-平滑肌肌动蛋白（SMA）、I型胶原蛋白和转化生长因子(TGF)-β mRNA水平升高有关。与假手术组相比，UUO组阻塞肾AngII含量明显升高，at1受体mRNA水平明显升高。相比之下，UUO仓鼠血管紧张素转换酶（ACE）蛋白表达显著降低。在UUO仓鼠中，CI或奥美沙坦治疗显著降低肾组织AngII水平和α-SMA、I型胶原和TGF-β mRNA水平，改善小管间质损伤。另一方面，CI和奥美沙坦均未改变收缩压、肾ACE和at1受体蛋白水平。这些数据表明，食糜依赖性的肾内AngII形成参与了仓鼠梗阻肾间质纤维化的发病机制。
Recent studies indicate a role of chymase in the regulation of angiotensin II (AngII) formation in cardiovascular and renal tissues. We investigated a possible contribution of chymase to AngII formation and to renal fibrosis in unilateral ureteral obstruction (UUO). Eight-week-old Syrian hamsters were subjected to UUO and treated with vehicle, the specific chymase inhibitor (CI) 4-[1-(4-methyl-benzo[b]thiophen-3-ylmethyl)-1H-benzimidazol-2-ylsulfanyl]-butyric acid (50 mg/kg, twice a day, p.o.), or the selective AT1-receptor blocker olmesartan (10 mg/kg per day, p.o,) for 14 days. UUO-induced renal interstitial fibrosis was associated with increases in renal mRNA levels of α-smooth muscle actin (SMA), type I collagen, and transforming growth factor (TGF)-β. The UUO hamsters showed markedly higher AngII contents and increased AT1-receptor mRNA level in the obstructed kidney than sham-operated ones. In contrast, angiotensin-converting enzyme (ACE) protein expression was significantly lower in UUO hamsters. In UUO hamsters, treatment with CI or olmesartan significantly decreased AngII levels in renal tissue and mRNA levels of α-SMA, type I collagen, and TGF-β and ameliorated tubulointerstitial injury. On the other hand, neither CI nor olmesartan changed systolic blood pressure, renal ACE, and AT1-receptor protein levels. These data suggest that chymase-dependent intrarenal AngII formation contributes to the pathogenesis of interstitial fibrosis in obstructed kidneys of hamsters.
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影响因子：
19.6
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Nishiyama, A;Yoshizumi, M;Abe, Y
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