Cyclooxygenase-2-selective inhibitors impair glomerulogenesis and renal cortical development.
Cyclooxygenase-2-selective inhibitors impair glomerulogenesis and renal cortical development.
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环加氧酶 2 选择性抑制剂会损害肾小球生成和肾皮质发育。
DOI：
10.1046/j.1523-1755.2000.00861.x
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Breyer,MD
中科院分区：
文献类型：
--
作者：
Komhoff,M;Wang,JL;Cheng,HF;Langenbach,R;McKanna,JA;Harris,RC;Breyer,MD
考克斯-2-选择性抑制剂损害肾小球和肾皮质发育。背景非甾体抗炎药（NSAIDs）的围产期暴露与人类肾发育不全有关。andin situhybridization.ResultsAdministration的考克斯-2-选择性抑制剂（SC 58236），在怀孕期间开始，直到断奶，显着损害的发展，肾皮质和减少肾小球直径在小鼠和大鼠。在考克斯-2 -/-小鼠中证明了相同的表型。与其对肾脏发育的影响相反，考克斯-2抑制剂对成年小鼠的肾小球体积没有影响。这种效应对考克斯-2具有特异性，因为母体给予考克斯-1选择性抑制剂（SC 58560）尽管显著抑制了幼鼠胃粘膜前列腺素E2（PGE 2）的合成，但并未影响肾脏发育。考克斯-2免疫反应阳性表达在出生后第1周达到高峰，并定位于S形体和皮质致密斑。治疗考克斯-2抑制剂在此期间（从出生后0天至21天）严重减少肾小球直径，而治疗仅限于怀孕并不影响肾小球size.ConclusionThese数据表明，考克斯-2活性在啮齿动物肾发生的重要作用，并定义一个特定的时间段的易感性，这些影响。
Cyclooxygenase-2–selective inhibitors impair glomerulogenesis and renal cortical development.BackgroundAntenatal exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with renal dysgenesis in humans.MethodsThese studies characterized cyclooxygenase-2 (COX-2) versus COX-1–selective inhibition on nephrogenesis in the rodent using histomorphometry, immunohistology, andin situhybridization.ResultsAdministration of a COX-2–selective inhibitor (SC58236), started during pregnancy until weaning, significantly impaired development of the renal cortex and reduced glomerular diameter in both mice and rats. An identical phenotype was demonstrated in COX-2 -/- mice. In contrast to its effects on the developing kidney, a COX-2 inhibitor had no effect on glomerular volume in adult mice. This effect was specific for COX-2 because maternal administration of a COX-1–selective inhibitor (SC58560) did not affect renal development despite significantly inhibiting gastric mucosal prostaglandin E2(PGE2) synthesis in pups. The expression of COX-2 immunoreactivity peaked in the first postnatal week and was localized to S-shaped bodies and the macula densa in the cortex. Treatment with a COX-2 inhibitor during this period (from postnatal day 0 to day 21) severely reduced glomerular diameter, whereas treatment limited to pregnancy did not affect glomerular size.ConclusionThese data demonstrate an important role for COX-2 activity in nephrogenesis in the rodent, and define a specific time period of susceptibility to these effects.
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DOI：
10.1152/ajprenal.1998.274.3.f481
发表时间：
1998-03
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Tianxin Yang;I. Singh;H. Pham;Daqing Sun;A. Smart;J. Schnermann;J. Briggs
通讯作者：
Tianxin Yang;I. Singh;H. Pham;Daqing Sun;A. Smart;J. Schnermann;J. Briggs
DOI：
10.1152/ajprenal.1997.272.4.f460
发表时间：
1997-04-01
影响因子：
4.2
作者：
Komhoff, M;Grone, HJ;Nusing, RM
通讯作者：
Nusing, RM
影响因子：
15.9
作者：
HARRIS, RC;MCKANNA, JA;BREYER, MD
通讯作者：
BREYER, MD
DOI：
10.1016/s0021-9258(18)98774-0
发表时间：
1991-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. Kujubu;B. Fletcher;B. Varnum;R. Lim;H. Herschman
通讯作者：
D. Kujubu;B. Fletcher;B. Varnum;R. Lim;H. Herschman
非甾体抗炎药引起的肾衰竭：环加氧酶亚型作用的简要回顾。
影响因子：
3.2
作者：
Venturini Cm;P. Isakson;P. Needleman
通讯作者：
P. Needleman