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Antiprotease of pulmonary fibrosis Using Micro Two-Dimensional Electorophoretic Analysis

使用微二维电泳分析抗肺纤维化蛋白酶

基本信息

批准号：
11660318
负责人：
SAKAGUTI Kazuko
金额：
$ 1.34万
依托单位：
Azabu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

We examined antiprotease (specifically, a_2-macrogrobulin : a_2-M) and ceruloplasmin (Cp) employing micro two-dimensional electrophoretic (M2D-PAGE) analysis to determine the characteristics of paraquat poisoned rats and rabbits that were not exhibiting paraquat induced pulmonary fibrosis.Rats were subjected to subacute exposure to PQ (at a dose of 7 mg/kg by s.c. administration once a day on 6-9 settings of administration). They were divided into a group of death from subacute toxicity, a group of rats with recovery from subacute toxicity and progression to pulmonary fibrosis, and a group of rats resistant to PQ. The rats with the fatal outcome from subacute toxicity showed a remarkable increase in α_2M-1. The rats, which escaped death from subacute toxicity and showed progression to pulmonary fibrosis, showed remarkable decreases in α_2M-2, α_2M-3, and α_2M-4 and α_1AT. The rats that were resistant to PQ showed relative increases in all molecular species of α_2M. Particularly the increases in major α_2M molecular species, α_2M-1 and α_2M-4, and a minor molecular species, α_2M-3, were characteristically observed in the rats.The rabbits with subacute PQ toxicity exhibited an increase in the early stage followed by a decrease in the later stage of the experimental reriod for the α_2M-1. In additon, a delayed increase in the α_2M-2 throughout the experimental period was documented. Our result indicate that the biological significance of α_2M components (α_2M-1 and α_2M-2) in the rabbit may constitute a species difference for PQ toxicity.

我们采用微二维电泳 (M2D-PAGE) 分析检查了抗蛋白酶（特别是 a_2-巨球蛋白：a_2-M）和铜蓝蛋白 (Cp)，以确定百草枯中毒大鼠和兔子的特征，但未表现出百草枯诱导的肺纤维化。对大鼠进行亚急性暴露于 PQ（剂量为 7 毫克/千克（SC）每天给药一次，给药次数为 6-9 次）。将其分为亚急性毒性死亡组、亚急性毒性恢复并进展为肺纤维化组大鼠、对PQ耐药组大鼠。因亚急性毒性导致致命结果的大鼠显示α_2M-1显着增加。逃脱亚急性毒性死亡并进展为肺纤维化的大鼠，α_2M-2、α_2M-3、α_2M-4 和 α_1AT 显着下降。对PQ有抵抗力的大鼠显示所有α_2M分子种类相对增加。特别是在大鼠中观察到主要α_2M分子种类α_2M-1和α_2M-4以及次要分子种类α_2M-3的增加。亚急性PQ毒性的家兔在实验过程中α_2M-1表现出早期增加，后期减少。此外，记录了整个实验期间 α_2M-2 的延迟增加。我们的结果表明，α_2M成分（α_2M-1和α_2M-2）在兔子体内的生物学意义可能构成PQ毒性的物种差异。