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慢性肾脏病病人中长期、大剂量应用Candesartan的非
Chen Yu*,, Rujun Gong*, Abdlla Rifai, Evelyn M. Tolbert* and Lance D. Dworkin*
* Division of Renal Disease, Department of Medicine, and Department of Pathology, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island; and Department of Nephrology, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China
Address correspondence to: Dr. Lance D. Dworkin, Division of Renal Disease, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903. Phone: 401-444-6843; Fax: 401-444-6849; E-mail: ldworkin@lifespan.org
Received for publication July 21, 2006. Accepted for publication January 2, 2007.
Recent evidence suggests that higher-than-usual antihypertensive dosages of renin-angiotensin-aldosterone system blockers may provide additional protection from progression of chronic renal disease; however, there have been few long-term studies, and the underlying mechanisms remain uncertain. This study examined the effects of long-term (14 mo) administration of ultrahigh dosages of the angiotensin receptor blocker candesartan on the progression of renal injury in spontaneously hypertensive rats (SHR). Beginning 8 wk after birth, SHR underwent unilateral nephrectomy and were given vehicle (control), or candesartan at a standard 5 mg/kg per d (T5), high 25 mg/kg per d (T25), or ultrahigh 75 mg/kg per d dosage (T75). After 2 wk, BP was reduced in all treated groups; however, it was better controlled in the high-dosage groups (T25 and T75). Urinary protein was significantly reduced in T75 after 2 wk of treatment and was also declined in the other two treatment groups but only after 2 mo. Exogenous angiotensin II test showed that complete angiotensin receptor blockade was achieved only in the high-dosage groups. Renal inflammation and macrophage (ED-1) infiltration were significantly ameliorated in both T25 and T75 but not in T5 rats. This was associated with the changes of tubular expression of monocyte chemoattractant protein-1, RANTES (regulated upon expression normal T cell expressed and secreted), and the phosphorylated NF-B, a marker for activation. Suppression of ED-1, monocyte chemoattractant protein-1, and RANTES expression and NF-B activation were greater in T75 as compared with T25. These findings suggest that candesartan has dosage-dependent, anti-inflammatory effects that are mediated by suppression of NF-B activation and chemokine expression. Renal protection with high-dosage therapy may depend on these nonhemodynamic effects. Recent evidence suggests that higher-than-usual antihypertensive dosages of renin-angiotensin-aldosterone system blockers may provide additional protection from progression of chronic renal disease; however, there have been few long-term studies, and the underlying mechanisms remain uncertain.
近期的研究证据显示，超常剂量应用具降压作用的肾素-血管紧张素-醛固酮系统阻滞剂另外可阻碍慢性肾病的进展。然而有关的长期研究极少，其根本机制尚未清楚。
This study examined the effects of long-term (14 mo) administration of ultrahigh dosages of the angiotensin receptor blocker candesartan on the progression of renal injury in spontaneously hypertensive rats (SHR)（自发性高血压大鼠）. Beginning 8 wk after birth, SHR underwent unilateral nephrectomy（单肾切除术） and were given vehicle 红色标记的地方不确定。
多谢指教。 (regulated upon expression normal T cell expressed and secreted),
我想这句话可能是打掉了一个逗号，另外expression似乎应是activation。
RANTES：调节激活正常T细胞表达和分泌因子。
confusing wrote:
(regulated upon expression normal T cell expressed and secreted),
我想这句话可能是打掉了一个逗号，另外expression似乎应是activation。
RANTES：调节激活正常T细胞表达和分泌因子。
谢谢各位战友捧场，因本人目前在国外，所以只有晚间（国内时间早晨）上线，所以各位热心战友提前帮我修改好，谢谢！
最近研究证据提示，超常规大剂量使用肾素-血管紧张素-醛固酮系统阻滞剂类的降压药可以获得额外的阻滞慢性肾病进展的肾保护作用。但目前仍缺乏相关的长期研究的资料，其（额外的肾保护作用）内在机制尚不清楚。
本研究观察了长期( 14个月）、超高剂量应用坎地沙坦（血管紧张素受体阻滞剂）对SHR大鼠（自发性高血压大鼠）肾损伤进展的影响。8周龄的SHR大鼠在接受单侧肾切除术后，分别接受了安慰剂（对照组），每天5 mg/kg坎地沙坦（T5）（标准剂量组），每天25 mg/kg (T25)（高剂量组），和每天75 mg/kg (T75)（超高剂量组）的治疗。
术后两周，所有治疗组大鼠血压均有所降低；高剂量组（T25 和T75）大鼠血压控制较好。超高剂量组（T75）大鼠在治疗两周后，尿蛋白量大大减少，而在另两个治疗组，两月后尿蛋白量才有所降低。外源性血管紧张素II灌注试验发现只有在高剂量组(T25 and T75)，血管紧张素受体才能被完全阻断。在高剂量组和超高剂量组（T25 和T75）肾脏炎症和巨噬细胞浸润得到显著改善而在标准剂量组（T5）则没有类似改变。阅读本文的人还阅读：
作者:admin@医学,生命科学 2011-02-09 17:14
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