中文摘要：

目的：观察一种化学合成小分子物质MCC950对线粒体损伤相关分子模式（MTDs）诱导肺泡巨噬细胞炎症反应的影响，并分析其可能的机制。方法利用差速离心法提取SD大鼠肝脏组织来源的MTDs。体外培养大鼠肺泡巨噬细胞NR8383细胞株，并分为空白对照组、LPS阳性对照组（1mg/LLPS刺激12h）、MTDs组（50、100、200mg/LMTDs刺激12h）、MCC950组（0.1μmol/LMCC950处理30min）、MCC950＋MTDs组（终浓度0.001、0.01、0.1、1.0μmol/LMCC950预处理30min＋100mg/LMTDs刺激12h）5组。收集各组细胞上清液及细胞，采用酶联免疫吸附试验（ELISA）检测肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-1β、IL-18）含量；采用蛋白质免疫印迹试验（WesternBlot）检测细胞中天冬氨酸特异性半胱氨酸蛋白酶1及其前体（caspase-1、pro-caspase-1）、IL-1β及其前体（pro-IL-1β）的蛋白表达。结果①与空白对照组相比，50、100、200mg/L的MTDs刺激组细胞上清液中TNF-α、IL-1β、IL-18含量均显著升高〔TNF-α（ng/L）：459.17±66.71、968.27±124.29、1128.6±172.02比34.67±11.66，IL-1β（ng/L）：341.57±38.09、685.00±75.36、784.97±89.28比26.33±8.04，IL-18（ng/L）：175.87±37.43、364.23±39.24、370.60±44.55比73.77±12.10，均P＜0.05〕，且呈剂量依赖性；并与LPS组具有类似的致炎作用。②与MTDs组相比，0.01、0.1及1.0μmol/LMCC950＋MTDs组细胞上清液中IL-1β、IL-18含量显著降低〔IL-1β（ng/L）：334.23±33.56、38.67±12.89、36.13±17.69比724.00±77.45，IL-18（ng/L）：165.77±25.47、71.37±5.99、66.80±14.61比412.23±40.15均P＜0.05〕，其中0.1μmol/L为产生抗炎作用的最佳有效浓度。而各浓度MCC950对TNF-α影响不大。③与MTDs组相比，0.01μmol/LMCC950＋MTDs组细胞中caspase-1及IL-1β蛋白表达显著下降（A值：14753.29±950.31比19222.50±1234.13，9981.06±673.63比12759.26±574.69，均P＜0.05），pro-caspase-1及pro-IL-1β蛋白表达无?

英文摘要：

Objective To observe the effect of a chemosynthetic small molecule substance MCC950 on the inflammatory mediators in alveolar macrophages （AM） induced by mitochondrial damage associated molecular patterns （mitochondrial DAMPs, MTDs）, and analyze its potential molecular mechanism. Methods Differential centrifugation was used to extract MTDs derived from liver of SD rat. The rat AM NR8383 cell was cultured in vitro, which was divided into five groups： blank control group, LPS positive control group （stimulated with 1 mg/L LPS for 12 hours）, MTDs group （stimulated with 50, 100, 200 mg/L MTDs for 12 hours）, MCC950 group （stimulated with 0.1 μmol/L MCC950 for 30 minutes）, and MCC950＋MTDs group （stimulated with 0.001, 0.01, 0.1, 1.0 μmol/L MCC950 for 30 minutes before stimulated with 100 mg/L MTDs for 12 hours）. The supernatants and cells of each group were collected, and the enzyme-linked immunosorbent assay （ELISA） was used to assay the contents of tumor necrosis factor-α （TNF-α）, interleukins （IL-1β and IL-18）, the Western Blot was used to assay the expression of caspase-1, pro-caspase-1, IL-1β and pro-IL-1β in the cell. Results ① Compared with the blank control group, the contents of TNF-α, IL-1β, IL-18 insupernatants in the 50, 100 and 200 mg/L MTDs group were significantly higher [TNF-α （ng/L）： 459.17±66.71, 968.27±124.29, 1 128.6±172.02 vs. 34.67±11.66, IL-1β（ng/L）： 341.57±38.09, 685.00±75.36, 784.97±89.28 vs. 26.33±8.04, IL-18 （ng/L）： 175.87±37.43, 364.23±39.24, 370.60±44.55 vs. 73.77±12.10, all P 〈 0.05], in a dose-dependent manner; with the similar inflammatory effect in lipopolysaccharide （LPS） positive control group. ② Compared with the MTDs group, the contents of IL-1β, IL-18 in the 0.01, 0.1 and 1.0 μmol/L MCC950＋MTDs group were rcmarkably decreased [IL-1β （ng/L）： 334.23±33.56, 38.67±12.89, 36.13±17.69 vs. 724.00±77.45, IL-18 （ng/L）： 165.77±25.47, 71.37±5.99, 66.80±14.61 vs. 412.23±40.15, al