He MDA production, all the IR groups showed higher value than the sham group (F = 120.34; IR-C vs sham and IR-NS vs sham, both P < 0.001; IR-RV vs sham, P = 0.049).Zhao et al. J MK-1439MedChemExpress MK-1439 Transl Med (2016) 14:Page 7 ofFig. 3 The effects of RvD1 on IR-induced energy metabolism in lung tissues. At T2, lung tissue was collected immediately after the IR procedure was completed and kept frozen in liquid nitrogen. Na+ +-ATPase activity, glycogen, lactic acid, and ATP, ADP were measured as described in “Methods” section. a Na+ +-ATPase; b glycogen; c lactic acid; d ATP; e ADP; f ATP/ADP. Data were analyzed by one-way ANOVA and unpaired-samples T test. n = 10 for each group *P < 0.05 for comparisons of IR-C, IR-NS and IR-RV groups with Sham group; #P < 0.05 for comparisons of IR-NS and IR-RV groups with IR-C groupHowever, after the using of RvD1, MDA production was significantly reduced in IR-RV group (F = 81.51; IR-NS vs IR-C, P = 0.170; IR-RV vs IR-C, P < 0.001).Effect of RvD1 on LIRIinduced cell apoptosisThe effect of RvD1 on lung tissue cell apoptosis at T2 was shown in Fig. 5a. Cells with apoptotic morphological features and with tan or brown nuclei were judged to be apoptotic cells. In Fig. 5a, only several apoptotic cells existed in the sham group, however, the number of apoptotic cells increased significantly in the IR-C and IR-NS group. Interestingly, after the treatment with RvD1, the apoptotic cells were decreased in the IR-RV group. In terms of the AI (Fig. 5b), the three IR groups showed much higher values than the sham group (F = 77.05; all P < 0.001). No difference was found between the IR-C and IR-NS group. However, compared to the IR-C group, the AI in IR-RV was significantly reduced (F = 31.08; IR-NS vs IR-C, P = 0.647; IR-RV vs IR-C, P < 0.001).Discussion LIRI is a pathological phenomenon, which refers to the rapid exacerbation of lung injury when lung tissue suffers from ischemia for a period and then blood supply is restored. Since LIRI happens more and more frequently in clinical practice in recent years, it is necessary toinvestigate its related mechanisms and the preventive or treatment methods [1, 23, 24]. Yet, the pathogenesis of the LIRI has not been fully clarified. Although many drugs were reported that they can reduce the LIRI in animal experiments, it is still very difficult to apply them into clinic due to their unsatisfactory effects or side effects [25?8]. Therefore, finding the safe and effective medications will provide great medical applications for the treatment of LIRI. The purchase XAV-939 research about the mechanisms of LIRI has been focused on the following aspects: oxygen radicals, lipid peroxidation and excessive inflammatory response caused by neutrophil infiltration PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27532042 and inflammatory mediators [29]; however, there is very little research to study the energy metabolism disorder and its prevention, which was considered to be one of the causes of the LIRI and an important link in the pathogenesis of many other diseases [8, 30, 31]. Since the discovery of lipoxins, Rv has become a new lipid molecule that can reduce the inflammation and protect the tissue structure by restraining the proliferation of neutrophils, macrophages and other inflammatory cells [32?5]. The research about the protective effect of Rv on the IRI organs has just started and only few reports about the heart, brain and intestines can be found [14, 15, 36]. However, the effects of RvD1 on LIRI are still unknown.Zhao et al. J Transl Med (2016) 14:Pag.He MDA production, all the IR groups showed higher value than the sham group (F = 120.34; IR-C vs sham and IR-NS vs sham, both P < 0.001; IR-RV vs sham, P = 0.049).Zhao et al. J Transl Med (2016) 14:Page 7 ofFig. 3 The effects of RvD1 on IR-induced energy metabolism in lung tissues. At T2, lung tissue was collected immediately after the IR procedure was completed and kept frozen in liquid nitrogen. Na+ +-ATPase activity, glycogen, lactic acid, and ATP, ADP were measured as described in "Methods" section. a Na+ +-ATPase; b glycogen; c lactic acid; d ATP; e ADP; f ATP/ADP. Data were analyzed by one-way ANOVA and unpaired-samples T test. n = 10 for each group *P < 0.05 for comparisons of IR-C, IR-NS and IR-RV groups with Sham group; #P < 0.05 for comparisons of IR-NS and IR-RV groups with IR-C groupHowever, after the using of RvD1, MDA production was significantly reduced in IR-RV group (F = 81.51; IR-NS vs IR-C, P = 0.170; IR-RV vs IR-C, P < 0.001).Effect of RvD1 on LIRIinduced cell apoptosisThe effect of RvD1 on lung tissue cell apoptosis at T2 was shown in Fig. 5a. Cells with apoptotic morphological features and with tan or brown nuclei were judged to be apoptotic cells. In Fig. 5a, only several apoptotic cells existed in the sham group, however, the number of apoptotic cells increased significantly in the IR-C and IR-NS group. Interestingly, after the treatment with RvD1, the apoptotic cells were decreased in the IR-RV group. In terms of the AI (Fig. 5b), the three IR groups showed much higher values than the sham group (F = 77.05; all P < 0.001). No difference was found between the IR-C and IR-NS group. However, compared to the IR-C group, the AI in IR-RV was significantly reduced (F = 31.08; IR-NS vs IR-C, P = 0.647; IR-RV vs IR-C, P < 0.001).Discussion LIRI is a pathological phenomenon, which refers to the rapid exacerbation of lung injury when lung tissue suffers from ischemia for a period and then blood supply is restored. Since LIRI happens more and more frequently in clinical practice in recent years, it is necessary toinvestigate its related mechanisms and the preventive or treatment methods [1, 23, 24]. Yet, the pathogenesis of the LIRI has not been fully clarified. Although many drugs were reported that they can reduce the LIRI in animal experiments, it is still very difficult to apply them into clinic due to their unsatisfactory effects or side effects [25?8]. Therefore, finding the safe and effective medications will provide great medical applications for the treatment of LIRI. The research about the mechanisms of LIRI has been focused on the following aspects: oxygen radicals, lipid peroxidation and excessive inflammatory response caused by neutrophil infiltration PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27532042 and inflammatory mediators [29]; however, there is very little research to study the energy metabolism disorder and its prevention, which was considered to be one of the causes of the LIRI and an important link in the pathogenesis of many other diseases [8, 30, 31]. Since the discovery of lipoxins, Rv has become a new lipid molecule that can reduce the inflammation and protect the tissue structure by restraining the proliferation of neutrophils, macrophages and other inflammatory cells [32?5]. The research about the protective effect of Rv on the IRI organs has just started and only few reports about the heart, brain and intestines can be found [14, 15, 36]. However, the effects of RvD1 on LIRI are still unknown.Zhao et al. J Transl Med (2016) 14:Pag.