论文部分内容阅读
目的阐明全氟异丁烯(perfluoroisobutylene,PFIB)吸入暴露致大鼠急性肺损伤形成过程中肺组织内基质金属蛋白酶-2(matrix metalloproteinase 2,MMP-2)和基质金属蛋白酶-9(MMP-9)的变化规律,评价分析盐酸四环素(tetracycline hydrochloride,TET)对大鼠PFIB吸入性急性肺损伤(acute lung injury,ALI)的治疗作用及其作用机制,为临床防治化学源性肺损伤提供参考。方法自制大鼠全身暴露动态吸入染毒系统构建大鼠PFIB吸入性ALI模型。在PFIB暴露前后不同时间采集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和组织样品,测定肺系数、BALF中蛋白质和磷脂,并采用酶谱分析检测BALF和肺组织中MMP-2和MMP-9活性。结果亚致死剂量PFIB吸入暴露可诱导形成典型的ALI。在正常大鼠肺组织中MMP-2和MMP-9活性极低,在BALF中几乎检测不到MMP-9。在亚致死剂量PFIB染毒组大鼠肺组织和BALF中,MMP-2活性显著性升高,而且其前体pro-MMP-2活性亦出现显著性升高;MMP-9仅观察到升高的趋势性变化,但差异无统计学意义。TET治疗能够显著改善PFIB吸入性急性肺损伤,而且能剂量依赖性的抑制肺组织和BALF中MMP-2活性,高剂量TET治疗可使肺组织中MMP-2活性降低至正常水平;其对pro-MMP-2的结果也相似。结论 pro-MMP-2与MMP-2在PFIB吸入性急性肺损伤大鼠肺组织和BALF中表达水平显著升高,且与ALI的进程高度一致;TET治疗能够显著下调pro-MMP-2与MMP-2的表达,从而减轻肺组织的损伤。提示这些MMPs在吸入PFIB所致ALI的发生过程中可能起着重要作用。
OBJECTIVE: To investigate the effects of perfluoroisobutylene (PFIB) inhalation on the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) (TET) on acute lung injury (PFI) induced by PFIB in rats and its mechanism of action, so as to provide reference for clinical prevention and treatment of chemical-induced lung injury. Methods Whole body exposed dynamic inhalation and exposure system was used to establish rat PFIB inhaled ALI model. Bronchoalveolar lavage fluid (BALF) and tissue samples were collected at different times before and after PFIB exposure. Pulmonary coefficient, protein and phospholipid in BALF were measured. The expression of MMP-2 and MMP- 9 activity. Results Sub-lethal dose PFIB inhalation exposure induced the formation of typical ALI. MMP-2 and MMP-9 activity in lung tissue of normal rats was extremely low, and almost no MMP-9 was detected in BALF. MMP-2 activity was significantly increased in the lung tissue and BALF of the sublethal PFIB-treated rats, and the pro-MMP-2 activity was also significantly increased in the sublethal PFIB-treated rats; only MMP-9 was found to be elevated The trend of change, but the difference was not statistically significant. TET treatment can significantly improve PFIB inhalation induced acute lung injury, but also dose-dependent inhibition of lung tissue and BALF activity of MMP-2, high-dose TET treatment can reduce the activity of MMP-2 in lung tissue to normal levels; its pro The results for MMP-2 are similar. Conclusion The expression of pro-MMP-2 and MMP-2 in the lung and BALF of PFIB-induced acute lung injury rats was significantly increased, which was highly consistent with the progression of ALI. TET treatment could significantly down-regulate the expressions of pro-MMP-2 and MMP-2 -2 expression, thereby reducing lung tissue damage. These MMPs may play an important role in the inhalation of PFIB-induced ALI.