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【文摘发布】长时间大剂量服用坎地沙坦抑制慢
Long-Term, High-Dosage Candesartan Suppresses Inflammation and Injury in Chronic Kidney Disease: Nonhemodynamic Renal Protection
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
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. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 J Am Soc Nephrol 18: 750-759, 2007
美国肾病学会杂志 2007年 第18卷，750-759页
Long-Term, High-Dosage Candesartan Suppresses Inflammation and Injury in Chronic Kidney Disease: Nonhemodynamic Renal Protection
长时间大剂量服用坎地沙坦抑制慢性肾脏疾病炎症和损伤:非血流动力学肾脏保护作用
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.
最近的证据表明 高于通常抗高血压剂量的肾素-血管紧张素-醛固酮系统阻滞剂可能对慢性肾病的进展提供额外的保护。然而 很少的长期研究（涉及此问题），其潜在的机制仍然不明确。
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).
该研究调查了超高剂量的血管紧张素受体阻滞剂坎地沙坦对自发性高血压大鼠的肾损伤进展的长期效应（14个月）。
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).
出生后8周，自发性高血压大鼠行单侧肾切除术，并接受给药，分别为赋形物（安慰剂）（对照组）；和以标准的5mg/kg•d（T5），高的25mg/kg•d（T25），或者超高的75mg/kg•d（T75）坎地沙坦。
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.
2周后，所有治疗组的血压减低，然而，在高剂量组(T25 和T75)血压得到较好的控制。2周后在T75治疗组尿蛋白显著降低，仅在2月后，其他两个治疗组的尿蛋白降低。
Exogenous angiotensin II test showed that complete angiotensin receptor blockade was achieved only in the high-dosage groups.
外源性血管紧张素Ⅱ试验表明，完全的血管紧张素受体封闭是仅仅在高剂量组取得。
Renal inflammation and macrophage (ED-1) infiltration were significantly ameliorated in both T25 and T75 but not in T5 rat s.
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作者:admin@医学,生命科学 2011-03-05 05:12
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