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.
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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.
肾脏炎症和巨噬细胞浸润在T25和T75组显著改善，但在T5组的大鼠则无。
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.
这（结果）和单核细胞趋化蛋白-1的管状表达，RANTES（调节正常T细胞表达与分泌的趋化因子）、和激活标志物phosphorylated NF-B的变化是相联系的
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.
这些研究表明，坎地沙坦是剂量依赖性、抗炎作用是通过抑制NF-B的活性和趋化因子表达介导的。高剂量的治疗的肾保护作用可能依赖这些非血流动力学的效应。
编译后：580字
最近的研究表明，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的肾脏保护作用可能依赖于非血流动力学的效应。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。学者们就此设计了动物试验进行证实。研究人员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）。研究人员对出生后8周的自发性高血压大鼠行单侧肾切除术，并接受给药，分别给安慰剂）（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。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。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。肾脏炎症和巨噬细胞浸润在T25和T75组显著改善，但在T5组的大鼠则无。这结果和单核细胞趋化蛋白-1的管状表达，调节正常T细胞表达与分泌的趋化因子以及NF-B活性变化是相联系的。研究人员认为，坎地沙坦是剂量依赖性、抗炎作用是通过抑制NF-B的活性和趋化因子表达介导的。高剂量的治疗的肾保护作用可能依赖这些非血流动力学的效应。研究成果发表在最新的《美国肾病学会杂志》上。
翻译内科的东东还是不顺手，请楼主指点
翻译得很好，可以看出来译者功底深厚。
tubular expression
在肾小管的表达。
confusing wrote:
翻译得很好，可以看出来译者功底深厚。
tubular expression
在肾小管的表达。
难得楼主一赞，呵呵