Tin-protoporphyrin prevents experimental superficial siderosis in rabbits
Tin-protoporphyrin prevents experimental superficial siderosis in rabbits
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DOI：
10.1093/jnen/61.8.689
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发表时间：
2002-08-01
影响因子：
3.2
通讯作者：
Dickson, AC
中科院分区：
文献类型：
--
作者：
Koeppen, AH;Dickson, AC
人中枢神经系统的浅表性黄素沉着症是由少量持续或反复的蛛网膜下腔出血引起的，这种出血导致含铁血黄素的破坏性沉积。过量的组织铁来自血红素，血红素氧化酶（HO）在一个限速步骤中被氧化，尤其是诱导形式HO-1。我们假设锡-原卟啉IX （SnPP）对HO的竞争性抑制可以预防实验性浅表性铁沉着。由于合成的金属卟啉不能穿过血脑屏障，SnPP直接进入大池。在1 ~ 16周的时间里，每周给家兔腹腔注射洗过的自体红细胞（RBC）。在配套实验中，SnPP加入红细胞悬浮液中，或不加红细胞注射SnPP。所有注射均引起小脑皮层伯格曼胶质细胞和梨状皮质浅层星形胶质细胞HO-1免疫反应性增加。注射红细胞或添加SnPP的红细胞也会产生强烈的小胶质细胞反应。金属卟啉以抑制量进入组织，并大大减少了组织化学可检测铁的积累。它并没有改变小胶质细胞的反应。观察结果表明，SnPP抑制血红素氧化，但不影响表面性铁沉着发病的其他步骤。
Superficial siderosis of the human central nervous system is caused by small continuous or recurrent subarachnoid hemorrhages that lead to the destructive deposition of hemosiderin. The excessive tissue iron derives from heme that is oxidized in a rate-limiting step by the enzyme heme oxygenase (HO), and especially the inducible form, HO-1. We postulated that competitive inhibition of HO by tin-protoporphyrin IX (SnPP) could prevent experimental superficial siderosis. Since synthetic metalloporphyrins do not cross the blood-brain barrier, SnPP was delivered directly into the cisterna magna. Rabbits received weekly intracisternal injections of washed autologous red blood cells (RBC) over a period of 1 to 16 wk. In companion experiments, SnPP was added to the suspension of RBC, or SnPP was injected without RBC. All injections caused increased HO-1 immunoreactivity in the Bergmann glia of the cerebellar cortex and in superficial astrocytes of the piriform cortex. The injections of RBC or RBC with added SnPP also generated a vigorous microglial response. The metalloporphyrin entered the tissue in inhibitory amounts and greatly reduced the accumulation of histochemically detectable iron. It did not alter the microglial response. The observations allowed the conclusion that SnPP suppressed heme oxidation but did not affect other steps in the pathogenesis of superficial siderosis.