Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes
Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes
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DOI：
10.1172/jci10228
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发表时间：
2001-04-01
影响因子：
15.9
通讯作者：
Anderson, S
中科院分区：
文献类型：
--
作者：
Korners, R;Lindsley, JN;Anderson, S
由环氧合酶（考克斯）产生的前列腺素（PGs）与糖尿病肾脏的病理性血流动力学和结构改变有关，但单个考克斯同工酶在糖尿病肾病中的作用尚不清楚。我们研究了中度高血糖、链脲佐菌素糖尿病（D）和对照（C）大鼠中COX-1和考克斯-2的表达以及对考克斯-1抑制剂水杨酸戊酰酯（VS）或考克斯-2抑制剂NS 338的血流动力学反应。免疫反应性考克斯-2增加D大鼠与C大鼠相比，并通过改善血糖控制正常化。NS 398的急性全身给药在C或D大鼠中均未诱导平均动脉压和肾血浆流量的显著变化，但在D大鼠中降低了肾小球滤过率，导致滤过分数降低。VS对D组大鼠肾血流动力学无明显影响。两种抑制剂均减少PGE的尿排泄（2）。然而，只有NS 398减少血栓素AL的排泄。总之，我们记录了肾皮质考克斯-2蛋白表达的增加与不同的肾血流动力学反应，选择性全身考克斯-2抑制D与C动物相比，表明考克斯-2衍生的PG在糖尿病病理性肾血流动力学变化中的作用。
Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown. We explored COX-I and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2 inhibitor NS338 in moderately hyperglycemic, streptozotocin-diabetic (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control. Acute systemic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerular filtration rate in D rats, resulting in a decrease in filtration fraction. VS had no effect on renal hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE(2). However, only NS398 reduced excretion of thromboxane AL. In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes.