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Objective:To evaluate the effects of bosutinib on acute lung injury in mice with endotoxemia.Methods:Sixty clean-grade healthy male C57BL/6 mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), bosutinib group (group B), endotoxemia group (group lipopolysaccharide [LPS]) and bosutinib plus endotoxemia group (group B+ LPS). Septic acute lung injury model was developed by intraperitoneal injection of LPS.Bosutinib 5 mg/kg was injected via the tail vein at 0.5 h before establishing the model in group B+ LPS and at the corresponding time point in group B. At 24 h after developing the model, the mice were sacrificed for microscopic examination of the pathological results of lung tissues which were scored for calculation of the lung coefficient (LI) and wet/dry lung weight (W/D) ratio, and for determination of the content of Evans blue in lung tissues (by Evans blue staining), expression of vascular endothelial cadherin (VE-cadherin), vascular cell adhesion molecule 1 (VCAM-1), phosphorylated nuclear transcription factor κB p65 (p-NF-κB p65), phosphorylated nuclear factor κB inhibitory protein α (pIκB-α) (by Western blot) and expression of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) mRNA (using real-time polymerase chain reaction). Results:Compared with group C, the LI, W/D ratio, Evans blue content in lung tissues and lung injury score were significantly increased, and the expression of IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, VCAM-1, p-NF-κB p65 and pIKB-α was up-regulated, and the expression of VE-cadherin was down-regulated in group LPS ( P<0.05), and no significant change was found in the parameters mentioned above in group B ( P>0.05). Compared with group B, the LI, W/D ratio, Evans blue content in lung tissues and lung injury score were significantly decreased, and the expression of IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, VCAM-1, p-NF-κB p65 and pIKB-α was down-regulated, and the expression of VE-cadherin was up-regulated in group LPS ( P<0.05). Conclusions:Bosutinib can ameliorate the acute lung injury in mice with endotoxemia.
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@#Objective To explore the association of Cyclophilin A，cerebral related blood indexes and carotid plaque’s formation and stability as well as cerebral infarction. Methods From December 2017 to December 2018，56 patients with acute cerebral infarction were admitted to cerebral infarction group；72 patients with carotid atherosclerotic plaques but no acute cerebral infraction were regarded as plaque group；40 healthy human who neither suffered from cerebral infarction nor carotid atherosclerotic plaques were divided into non-plague group；The degree of plaque stability in each group was expressed by plaque score. The higher the plaque score，the more unstable the plaque was；The content of CypA were determined by enzyme-linked immunosorbent assay，and the common blood indexes data were collected from the text results of medical records；Carotid artery plaque was detected by carotid artery ultrasound，and the plaque score was determined according to the morphology of carotid artery plaque in ultrasound. Results There were statistically significant differences in CyPA levels between the non-plague group and the non-cerebral infraction group.（P<0.05）. CyPA level was regarded as a risk factor for the development of carotid atherosclerosis plagues（OR=1.002，95%CI 0.824～1.219）. There was no statistical significance between CyPA levels and carotid artery plaque score（the stability of carotid atherosclerotic plaque）in cerebral infarction and non-cerebral infraction group. （P>0.05）. There was an significant difference in carotid atherosclerotic plaque score between the cerebral infarction group and plaque group. （P<0.05）. In cerebral infraction group，the content of fibrinogen and glycosylated hemoglobin were positively correlated with carotid atherosclerotic plaque score and the hemoglobin was negatively correlated with the carotid atherosclerotic plaque score，and these differences were statistically significant. （P<0.05）. Ordinal logistic regression showed that fibrinogen level was regarded as a risk factor for the development of carotid atherosclerosis plagues（OR=8.988，95%CI 3.017～3.422），hemoglobin level was regarded as a protective factor for the development of carotid atherosclerosis plagues（OR=0.936，95%CI 134.031～144.583）. In plaque group，the content of high-density lipoprotein have positive correlation with the carotid atherosclerotic score，and the difference is statistically significant. （P<0.05）. Ordinal logistic regression showed that high-density lipoprotein level was regarded as a protective factor for the development of carotid atherosclerosis plagues（OR=0.052，95%CI 1.237～1.364）. Conclusion The serum content of CyPA was a risk factor for the formation of carotid atherosclerosis plaque，but it was not related to the stability of the plaques. The degree of plaque instability in patients with acute cerebral infarction was significantly increased compared with the patients without cerebral infarction. For patients with acute cerebral infarction，the contents of fibrinogen and glycosylated hemoglobin were negatively correlated with the stability of carotid atherosclerotic plaques，hemoglobin content was positively correlated with the stability of carotid atherosclerotic plaques. Fibrinogen level was regarded as a risk factor for the development of carotid atherosclerosis plagues. Hemoglobin level was regarded as a protective factor for the development of carotid atherosclerosis plagues. For patients without acute cerebral infraction，the content of high-density lipoprotein was positively correlated with the stability of carotid atherosclerotic plaques and was regarded as a protective factor for the development of carotid atherosclerosis plagues.