Objective： To observe the role and mechanism of CO- releasing molecule （CORM）-2 in lung injury induced by ischemia-reperfusion （IR） of hind limbs in rats. Methods： Arat model of lung injury induced by IR of hind...Objective： To observe the role and mechanism of CO- releasing molecule （CORM）-2 in lung injury induced by ischemia-reperfusion （IR） of hind limbs in rats. Methods： Arat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley （SD） rats were randomly divided into 5 groups （n = 8）： sham, sham ＋ CORM-2, IR, IR ＋ CORM-2 and IR ＋ dimethyl sulfoxide （DMSO）. Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR＋CORM-2 group and in the sham ＋ CORM-2 group were given CORM-2 （10 μmol/kg intravenous bolus） 5 minutes before reperfusion or at the corresponding time points, while rats in the IR ＋ DMSO group was treated with the same dose of vehicle （DMSO） at the same time. The lung tissue structure, polymorphonuclear neutrophil （PMN） count, wet-to-dry weight ratio （W/D）, malondialdehyde （MDA） content, myeloperoxidase （MPO） activity, intercellular adhesion molecule- 1 （ICAM- 1）expression, I κBα degradation and nuclear factor （NF）-κB activity in the lungs were assessed. Results： As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF- κB activity significantly increased in the IR group, but the level of I κBα decresed （P〈0.01）. Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM- 1 expression significantly decreased in the IR＋COMR-2 group （P〈0.01）, while the level of IκBα increased. Conclusions： These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-κB pathway and the leu- kocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.展开更多
Enhanced inflammatory response and oxidative stress cause acute lung injury(ALI). Controlling inflammation and oxidation can ameliorate ALI. In the present study, we aimed to determine whether 3,4-Dihydroxyacetophenon...Enhanced inflammatory response and oxidative stress cause acute lung injury(ALI). Controlling inflammation and oxidation can ameliorate ALI. In the present study, we aimed to determine whether 3,4-Dihydroxyacetophenone(compound 1)could ameliorate lipopolysaccharide(LPS)-induced ALI by suppressing inflammation and oxidation. In this study, compound 1 reduced LPS-induced inflammatory cytokines and oxidative stress in RAW 264.7 cells. Moreover, compound 1 suppressed the expression of inflammatory protein p65, inhibited IkBα phosphorylation, decreased the nuclear translocation of p65, and increased the expressions of anti-oxidative protein nuclear factor erythroid 2-related factor 2(Nrf-2) and heme oxygenase-1(HO-1), which was reduced by LPS, in leukemia cells in mouse macrophage(RAW 264.7) cells. Furthermore, compound 1 could also ameliorate LPS-induced ALI in vivo, with a reduction of inflammatory cytokines, oxidative stress, and nuclear factor-kappa B(NF-κB)signaling pathway activation. This study emphasized the anti-inflammatory and anti-oxidative activities of compound 1, which could be a valuable therapeutic agent against ALI.展开更多
基金This project was supported by the National Natural Science Foundation of China （No. 30271337）.
文摘Objective： To observe the role and mechanism of CO- releasing molecule （CORM）-2 in lung injury induced by ischemia-reperfusion （IR） of hind limbs in rats. Methods： Arat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley （SD） rats were randomly divided into 5 groups （n = 8）： sham, sham ＋ CORM-2, IR, IR ＋ CORM-2 and IR ＋ dimethyl sulfoxide （DMSO）. Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR＋CORM-2 group and in the sham ＋ CORM-2 group were given CORM-2 （10 μmol/kg intravenous bolus） 5 minutes before reperfusion or at the corresponding time points, while rats in the IR ＋ DMSO group was treated with the same dose of vehicle （DMSO） at the same time. The lung tissue structure, polymorphonuclear neutrophil （PMN） count, wet-to-dry weight ratio （W/D）, malondialdehyde （MDA） content, myeloperoxidase （MPO） activity, intercellular adhesion molecule- 1 （ICAM- 1）expression, I κBα degradation and nuclear factor （NF）-κB activity in the lungs were assessed. Results： As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF- κB activity significantly increased in the IR group, but the level of I κBα decresed （P〈0.01）. Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM- 1 expression significantly decreased in the IR＋COMR-2 group （P〈0.01）, while the level of IκBα increased. Conclusions： These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-κB pathway and the leu- kocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.
基金National Natural Science Foundation of China (Grant No. 82003755)the Medical Technology Program of Ningbo (Grant No. 2019Y07)。
文摘Enhanced inflammatory response and oxidative stress cause acute lung injury(ALI). Controlling inflammation and oxidation can ameliorate ALI. In the present study, we aimed to determine whether 3,4-Dihydroxyacetophenone(compound 1)could ameliorate lipopolysaccharide(LPS)-induced ALI by suppressing inflammation and oxidation. In this study, compound 1 reduced LPS-induced inflammatory cytokines and oxidative stress in RAW 264.7 cells. Moreover, compound 1 suppressed the expression of inflammatory protein p65, inhibited IkBα phosphorylation, decreased the nuclear translocation of p65, and increased the expressions of anti-oxidative protein nuclear factor erythroid 2-related factor 2(Nrf-2) and heme oxygenase-1(HO-1), which was reduced by LPS, in leukemia cells in mouse macrophage(RAW 264.7) cells. Furthermore, compound 1 could also ameliorate LPS-induced ALI in vivo, with a reduction of inflammatory cytokines, oxidative stress, and nuclear factor-kappa B(NF-κB)signaling pathway activation. This study emphasized the anti-inflammatory and anti-oxidative activities of compound 1, which could be a valuable therapeutic agent against ALI.
