Antiprotease of pulmonary fibrosis Using Micro Two-Dimensional Electorophoretic Analysis

我们采用微二维电泳（M2D-PAGE）分析检测了抗蛋白酶（特别是a_2-macrogrobulin: a_2-M）和铜蓝蛋白（Cp），以确定未表现出百草枯诱导肺纤维化的百草枯中毒大鼠和家兔的特征。大鼠亚急性暴露于PQ（剂量为7 mg/kg，每天1次，分6-9次给药）。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和PQ耐药组。亚急性中毒致死性大鼠α 2m2 -1显著升高。亚急性毒性未死亡并进展为肺纤维化的大鼠α 22m -2、α 22m -3、α 22m -4和α_1AT均显著降低。抗PQ大鼠α_2M各分子种均相对升高。其中α_2M主要分子种α_2M-1、α_2M-4和α_2M-3的增加最为明显。亚急性PQ毒性家兔α 2m -1在实验前期呈升高趋势，在实验后期呈下降趋势。此外，α 22m -2在整个实验期间呈延迟性升高。结果表明，α_2M成分（α 22m -1和α 22m -2）在家兔体内的生物学意义可能构成了PQ毒性的种间差异。

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.