Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice
Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice
复制标题
糜抑素对百草枯所致小鼠急性肺损伤的保护作用
作者：
Chen Yang;Hong;Wei Liu;Xue;Zhi Liu
本研究旨在探讨抑糜蛋白酶在百草枯致急性肺损伤中的作用。将癌症研究所的小鼠随机分配到NS、DMSO、糜蛋白酶抑制剂、百草枯或糜蛋白酶抑制剂处理组中。在给药后0、1、2、4、8、12、24和48 h，每组6只小鼠腹腔注射水合氯醛。通过心脏穿刺采集血样。肺组织苏木精-伊红染色观察肺组织学变化。根据肺湿干比（W/D）确定肺水肿的程度。采用底物荧光法测定血清组织蛋白酶G活性。采用酶联免疫吸附法测定血清内皮细胞特异性分子-1（endocan）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1β）、白细胞介素-6（IL-6）和高迁移率族蛋白1（HMGB 1）水平。Western blot法检测肺组织内皮聚糖和核NF-κ Bp 65的表达水平。Chymostatin可减轻小鼠急性肺泡炎的病理改变，降低肺W/D比值，降低组织蛋白酶G活性，降低血清TNF-α、IL-1β、IL-6和HMGB 1浓度，升高血清内皮素浓度。Western blot结果显示，糜蛋白酶抑制剂上调肺组织内皮素表达，下调核因子NF-κ Bp 65表达。Chymostatin通过抑制组织蛋白酶G活性上调内皮素表达，间接抑制NF-κ Bp 65活性，逆转百草枯诱导的肺损伤炎症反应。
This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydrate at 0, 1, 2, 4, 8, 12, 24 and 48 h after treatment administration. Blood samples were collected through cardiac puncture. Lung tissues were stained with haematoxylin and eosin for the observation of lung histology. The degree of pulmonary oedema was determined on the basis of lung wet-to-dry ratio (W/D). The serum activity of cathepsin G was determined through substrate fluorescence assay. The serum levels of endothelial cell-specific molecule-1 (endocan), tumour necrosis factor-a (TNF-a), interleukin-1β (IL-1β), IL-6 and high-mobility group box protein 1 (HMGB1) were determined through enzyme-linked immunosorbent assay. The expression levels of endocan and nuclear NF-κBp65 in the lung were quantified through Western blot. Chymostatin alleviated the pathological changes associated with acute alveolitis in mice; decreased the lung W/D ratio, the activity of cathepsin G and the serum concentrations of TNF-a, IL-1β, IL-6 and HMGB1; and increased the serum concentration of endocan. Western blot results revealed that chymostatin up-regulated endocan expression and down-regulated nuclear NF-κBp65 expression in the lung. Chymostatin reversed the inflammatory effects of paraquat-induced lung injury by inhibiting cathepsin G activity to up-regulate endocan expression and indirectly inhibit NF-κBp65 activity.
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