IL6 suppression provides renal protection independent of blood pressure in a murine model of salt-sensitive hypertension
IL6 suppression provides renal protection independent of blood pressure in a murine model of salt-sensitive hypertension
复制标题
DOI：
10.1159/000104094
复制
发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Imig, J. D.
中科院分区：
文献类型：
--
作者：
Manhiani, M. M.;Quigley, J. E.;Imig, J. D.
细胞色素 P450 环氧化酶 (Cyp2c) 调节受损会导致血管紧张素盐敏感性高血压 (ANG/HS) 的肾损伤。我们假设白细胞介素 6 缺失小鼠 (IL6 -/ -) 可以改善 Cyp2c 调节并减少高盐饮食高血压小鼠的肾损伤。与血管紧张素 (ANG) 高血压相比，ANG/HS 高血压的收缩压升高程度更大，但 WT 和 IL6 -/ - 高血压组之间的血压没有差异。白蛋白尿是肾损伤的标志物，在 WT 小鼠的 ANG/HS 高血压中显着增加（5,113 +/- 1,050 μg/天），而在 ANG/HS IL6 -/ - 组中减弱（1,306 +/- 385 μg/天）。与单独高盐相比，WT 小鼠中 ANG/HS 高血压的肾 Cyp2c 蛋白表达显着降低。然而，ANG/HS IL6 缺陷的高血压小鼠恢复了响应高盐饮食而上调 Cyp2c 表达的能力。与 ANG/HS WT 组相比，ANG/HS IL6 -/ - 高血压小鼠中可溶性环氧化物水解酶的肾表达显着降低，该酶可灭活保护性环氧化酶代谢物。这些数据表明，IL6 虽然对血压没有影响，但会损害产生 Cyp2c 的环氧化酶的调节，这可能导致血管紧张素盐敏感性高血压中肾损伤的发生。
Impaired cytochrome P450 epoxygenase enzyme ( Cyp2c) regulation contributes to renal damage in angiotensin salt-sensitive hypertension ( ANG/ HS). We hypothesized that interleukin-6 null mice ( IL6 -/ -) would improve Cyp2c regulation and reduce renal damage in hypertensive mice fed a high salt diet. Systolic blood pressure increased to a greater extent in ANG/ HS hypertension as compared to angiotensin ( ANG) hypertension but blood pressure did not differ between WT and IL6 -/ - hypertensive groups. Albuminuria, a marker for renal injury, increased significantly in ANG/ HS hypertension in WT mice ( 5,113 +/- 1,050 mu g/ day) and was attenuated in the ANG/ HS IL6 -/ - group ( 1,306 +/- 385 mu g/ day). Renal Cyp2c protein expression significantly decreased with ANG/ HS hypertension in WT mice as compared to high salt alone. However, the ability to upregulate Cyp2c expression in response to a high salt diet was restored in the ANG/ HS IL6 deficient hypertensive mice. Renal expression of soluble epoxide hydrolase, which inactivates protective epoxygenase metabolites, was significantly reduced in ANG/ HS IL6 -/ - hypertensive mice compared to the ANG/ HS WT group. These data suggest that IL6, while having no effect on blood pressure, impairs regulation of epoxygenase producing Cyp2c, which could contribute to the development of renal injury in angiotensin salt- sensitive hypertension.