Antiprotease of pulmonary fibrosis Using Micro Two-Dimensional Electorophoretic Analysis

为了研究百草枯中毒大鼠和未出现百草枯诱导肺纤维化的家兔的抗蛋白酶（α_2-巨球蛋白：α_2-M）和铜蓝蛋白（Cp）的特征，我们采用微量双向电泳（M2 D-PAGE）技术对百草枯中毒大鼠和家兔的抗蛋白酶和铜蓝蛋白进行了检测。每天给药一次，给药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和PQ耐药组。亚急性毒性致死大鼠α_2M-1明显升高。在亚急性中毒后未死亡并发生肺纤维化的大鼠中，α_2M-2、α_2M-3、α_2M-4和α_1AT均显著降低。PQ抵抗组大鼠α_2M各分子种类均相对增加。结果表明，PQ对大鼠α_2M的主要分子α_2M-1、α_2M-4和次要分子α_2M-3均有不同程度的增加，而对亚急性PQ中毒家兔的α_2M-1则表现为早期增加，后期减少。此外，在整个实验过程中，α_2M-2的增加是延迟的。结果表明，α_2M组分（α_2M-1和α_2M-2）在家兔体内的生物学意义可能构成PQ毒性的种属差异。

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.