Induction of apoptosis during development of hypertensive nephrosclerosis.
Induction of apoptosis during development of hypertensive nephrosclerosis.
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DOI：
10.1111/j.1523-1755.2000.00373.x
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发表时间：
2000-11
影响因子：
19.6
通讯作者：
W. Ying;P. X. Wang;P. Sanders
中科院分区：
文献类型：
--
作者：
W. Ying;P. X. Wang;P. Sanders
随着程序性细胞死亡或凋亡的生物学被阐明，已经假设该过程在器官功能障碍和纤维化的病理生理学中的作用。高血压性肾硬化是终末期肾病的重要原因。进行性、非炎症性、硬化性高血压肾损害的一种模型是Dahl/Rapp盐敏感大鼠，本研究对其进行了研究。方法将雄性、Dahl/Rapp盐敏感（SS）和Sprague-Dawley大鼠分别给予0.3或8.0%NaCl饮食3周。测定血压，收获肾脏进行组织化学分析，并获得用于RNA酶保护测定的总RNA和用于Western印迹的总蛋白。结果高盐饮食组SS大鼠肾小球和肾小管细胞凋亡增加。这些发现发生在肾功能明显受损和肾形态发生不可逆变化的时候。与凋亡增加相关的是促凋亡分子Fas、Bax和Bcl-XS的表达增强。结论：促进肾单位凋亡的蛋白质表达的不适当变化，沿着肾功能恶化时表现出的持续细胞死亡，支持了这一过程在高血压肾硬化发展中的重要作用。
BACKGROUND As the biology of programmed cell death, or apoptosis, is clarified, a role for this process in the pathophysiology of organ dysfunction and fibrosis has been hypothesized. Hypertensive nephrosclerosis represents an important cause of end-stage renal disease. One model of the progressive, noninflammatory, sclerotic renal lesion of hypertension is the Dahl/Rapp salt-sensitive rat, which was examined in this study. METHODS Male, Dahl/Rapp salt-sensitive (SS) and Sprague-Dawley rats were placed on either 0.3 or 8.0% NaCl diets for three weeks. Blood pressure was determined, and the kidneys were harvested for histochemical analysis and to obtain total RNA for RNase protection assays and total protein for Western blotting. RESULTS An increase in apoptosis in the glomerular and tubular compartments was observed only in kidneys of SS rats on the high-salt diet. These findings occurred at a time when renal function was markedly impaired and irreversible changes in renal morphology developed. Temporally associated with this increase in apoptosis was augmented expression of pro-apoptotic molecules that included Fas, Bax, and Bcl-XS. CONCLUSIONS The inappropriate shift in expression of proteins that facilitate apoptosis in the nephron, along with ongoing cell death that manifested at a time when renal function was deteriorating, supported an important role for this process in development of hypertensive nephrosclerosis.