ABSTRACT
Objective To investigate the signal pathway of platelet activation in acute respiratory distress syndrome (ARDS). Methods Thirty healthy Sprague-Dawley (SD) rats were randomly divided into control group (n = 6) and model group (n = 24). The model of ARDS was reproduced by intravenous injection of oleic acid (0.25 mL/kg), and the rats in control group were injected with the same amount of normal saline. The blood of abdominal aorta was collected at 2, 6, 24, and 72 hours after model reproduction, the platelets were separated, and c-Jun N-terminal kinase phosphorylation (pJNK) levels which was one of major protein kinases in the mitogen-activated protein kinases (MAPKs) signal pathway was determined by Western Blot. The rats were sacrificed, the lung tissues were harvested, and lung coefficient (lung weight/body weight ×100%) and lung wet/dry (W/D) ratio were calculated. Pathological changes in the lung tissue were observed with hematoxylin-eosin (HE) staining in light microscope. Results Comp ared with the control group, platelet pJNK level in ARDS model group was significantly increased at 2 hours after model reproduction (gray value: 0.72±0.09 vs. 0.22±0.01), and peaked at 6 hours (gray value: 0.91±0.03 vs. 0.22±0.01), then it was decreased gradually. It was also significantly higher than that of control group till 72 hours after model reproduction (gray value: 0.39±0.06 vs. 0.22±0.01, all P < 0.05). Lung coefficient and lung W/D ratio in ARDS model group were significantly increased at 2 hours after model reproduction as compared with those of control group [(1.30±0.20)% vs. (0.60±0.10)%, 6.00±0.60 vs. 3.30±0.30], then they were decreased gradually. They were also significantly higher than those of control group till 72 hours after model reproduction [(0.90±0.10)% vs. (0.60±0.10)%, 4.80±0.70 vs. 3.30±0.30, all P < 0.05]. It was showed by light microscopy that lung tissue of rats in the control group had no significant pathological changes. At 2 hours after model reproduction in model group, clearly visible alveolar edema and interstitial edema, interstitial lung infiltration of inflammatory cells, small blood vessels dilation and congestion were found, and the re were a lot of protein exudates. The lesions of lung peaked at 24 hours. At 72 hours, absorption of most of fluid leaking in alveolar, alveolar space narrow, alveolar septum thickening, the reduction of inflammatory cells infiltration, fibrous tissue proliferation, and micro thrombosis formation were found. Conclusion In ARDS, in addition to pathological changes in the lung tissue, platelet activation occurs, and its activation process is related to the priming of JNK signal transduction pathways.
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AIM:To investigate the effects of antioxidant N-acetylcysteine(NAC)on the lipopolysaccharide(LPS)-induced MAPK phosphorylation in mouse liver.METHODS:54 male mice were divided into three groups:control(n=6),0.9% sodium chloride 0.2 mL ip;LPS group(n=24):LPS 5 mg ip;NAC+LPS group(n=24):NAC 150 mg?kg-1?d-1 ip,for 3 d;LPS 5 mg ip after 1 h of NAC administration at 3rd day.The liver was excised with carbrital anesthesia after LPS or 0.9 % sodium chloride injection at 0.5 h,1 h,2 h and 6 h for GSH and MDA assays.The protein extracted from liver was assayed for the phosphorylation of MEK1/2,ERK1/2,p38 MAPK by Western blotting.TNF-? in liver was assayed by radioimmunoassay.RESULTS:MDA in the liver was decreased remarkably and the GSH in the liver was increased significantly by NAC pretreatment.The phosphorylation of MEK1/2,ERK1/2 and p38 MAPK in liver were inhibited significantly by NAC pretreatment after LPS challenge.Meanwhile,TNF-? in liver was decreased markedly.CONCLUSION:Reactive oxygen species plays a critical role in MAPK signaling during the LPS induced acute liver injury.NAC partially inhibits LPS-induced MAPK signaling by antioxidant effect and decreases TNF-? production.
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AIM: To understand the effect of exogenous carbon substrate on the dynamic regulation of cardiac oxidative phosphorylation. METHODS: Method of mean response time measurement of the myocardial mitochondrial O 2 consumption (t mito ) was developed by van Beek. Glucose, lactate, or pyruvate as carbon substrate respectively for myocardial energy supply was perfused in isolated rabbit hearts with Tyrode solution at 37℃. RESULTS: When heart rate was stepped up from 120 to 140 and 220 (beat?min -1 ) respectively the t mito . We have measured was: (6.3?1.0) s and (7 4?0.9) s for glucose; (5.4?1.2) s and (7.0?0.9) s for lactate; (4.0?0.7)s and (6 5?0 6) s for pyruvate (two way ANOVA, P