Protective effect of MCC950 against lung injury induced by mitochondrial damage-associated molecular patterns / 医学研究生学报

ABSTRACT

Objective There is still no specific immuno-therapy to acute respiratory distress syndrome induced by severe trau-ma.The article aimed to investigate the effect of MCC 950 on lung in-jury induced by mitochondrial damage-associated molecular patterns ( MTDs) and preliminarily evaluate its molecular mechanism . Methods 40 SD rats were randomly devided into control group , MTDs group, MCC950 group, MTDs+MCC950 group.The rats were were taken MCC950 (20mg/kg) by peritoneal injection pretreatment for 1 hour, followed by tail vein injection of MTDs (5%liver vol-ume) and were killed 12 hours later.ELISA were applied to detect tumor necrosis factor (TNF-α), interleukin-1β( IL-1β) and IL-18 in broncho-alveolar lavage fluid ( BALF) , and BCA method to assess the content of total protein .Lung tissues were weighed to calculate lung wet weight/body weight( LWW/BW) ratio, and stained by HE staining to observe the pathological changes through light micro -scope.Smith lung injury score was used to assess histological lung injury .Western blot was employed to evaluate the protein expression of Pro-Caspase-1 and Caspase-1. Results ①Compared with control group , TNF-α, IL-1βand IL-18 in BALF of MTDs group were significantly increased( all P<0.05), but not in MCC950 group(P>0.05), TNF-αin BALF of MTDs +MCC950 group were signifi-cantly increased( all P<0.05), IL-1βand IL-18 were not(all P>0.05).Compared with MTDs group, IL-1βand IL-18 in BALF of MTDs +MCC950 group were in serious decline (all P<0.05).Compared with control group, the LWW/BW ratio [(4.19±0.36)mg/g vs (6.32±0.54)mg/g, P<0.05] and the content of total protein [(0.12±0.03)g/L vs (0.79±0.07)g/L, P<0.05] were dramatically increased.Compared with MTDs group, the LWW/BW ratio [(4.35±0.29)mg/g, (4.47±0.0.46)mg/g, P<0.05] and the content of total protein [(0.12±0.06)g/L, (0.15±0.06)g/L, P<0.05] were in serious decline.Smith lung injury score revealed that compared with control group the score of MTDs group was elevated (1.00±0.00 vs 8.33±0.58, P<0.05), and the score of MTDs+MCC950 group was significantly decreased than MTDs group ( 8.33±0.58 vs 3.67±0.58, P<0.05) .Compared with control group , the protein expres-sion of Pro-caspase-1 and caspase-1 were markedly improved (all P<0.05).However, the expression of caspase-1 was significantly milder than that in MTDs group ( P<0.05), the protein expression of Pro-caspase-1 was comparable ( P>0.05). Conclusion MCC950 exerts protective effect against lung injury induced by MTDs probably via the inhibition of NLRP 3 inflammasome activation .