Effects And Mechanism Of 7-nitroindazole On Smoke Inhalation Lung Injury In Rats

Objective:To establish an animal model of low saturation of blood oxygen with long-term and stabilization, used to assess smoke inhalation lung injury. To investigate the change of biochemistry in lung, as well as the progression of smoke inhalation lung injury. Then, to analysis the nosogenesis of smoke inhalation lung injury. To explore the safety of intraperitoneal injection, so building the ripe process of treatment. To investigate the effects and mechanism of 7-NI on smoke inhalation acute lung injury in rats.Methods:1. Establish the model of smoke inhalation lung injury in ratsForty male Sprague-Dawley rats weighing 300±20 g were used to experiment, 8 healthy rats of the same age were taken out randomly as control group(A group). The rest models of smoke inhalation lung injury were established according by the methods reported by Erfan Xie etc. in Burn Institute of the Third Military Medical University. The qualified models of smoke inhalation lung injury was in accordance with the standard of breathing rate greater than 30/min.2. Groups:The qualified rats were randomly divided into two groups: B group: smoke inhalation without treatment, received 2ml intraperitoneal injection of arachis oil after injury; C group: smoke inhalation and 7-NI treated, received 20mg/kg intraperitoneal injection of 7-NI after injury.3. Arterial blood gas analysisArterial blood gas analysis was monitored in batch at 2 hour,6 hour,12 hour and 24 hour.4. View index in vitroAfter rats were executed in batch at every time, pulmonary was observed. Pulmonary moisture was detected according by the way of dry/wet weight. Pulmonary moisture=( wet weight of lung-dry weight of lung)/ dry weight of lung. The unit is ml/g. Pulmonary was made into homogenate. The activity of hepatocuprein (SOD), catalase(CAT), the contents of tumor necrosis factor- alpha(TNF-α), inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and nitric oxide(NO) were detected in pulmonary homogenate. The pneumonic pathologic changes were observed, after pulmonary was fixed, embedded, sectioned and stained.Result:1. General state of health of rats94.1 percent of rats were qualified. It's breathing rate greater than 30/min. All rats were depressed. It's breathing was light and fast, accompany by wheezing rale. Compared with B group, C group was advanced.2. Effects of 7-NI on arterial partial pressure of oxygen of ratsArterial partial pressure of oxygen of rats in A group always sustained in high level (>96mmHg). Compare with A group, B group's arterial partial pressure of oxygen cut down 29.3 percent (29mmHg) after injury, and sustained in low level (<70mmHg) (p<0.05). Compare with B group, C group's arterial partial pressure of oxygen increased 19.5 percent (20mmHg) in 2 hour after injury, and sustained in high level (>80mmHg). In 24 hour after injury, C group's arterial partial pressure of oxygen achieved normal (96.4±5mmHg) (p<0.05).3. Effects of 7-NI on pulmonary moisture of ratsB group's pulmonary moisture increased significantly, C group's pulmonary moisture increased lightly. The difference of A, B and C group has statistical significance (p<0.05).4. Effects of 7-NI on biochemistry of smoke inhalation lung injuryAfter injury, the activity of SOD and CAT decreased. Compared with A group, the activity of SOD cut down 34 percent (16.4 U/gprot), the activity of CAT cut down 35 percent (31.3 U/gprot) ( p<0.05). After injury, the activity of nNOS and the content of NO in B group sustained in high level. Compared with A group, the activity of nNOS in B group was increased 1.3 times (6.44 U/gprot), the content of NO was increased 80 percent (4.54μmol/gprot) (p<0.05). After injury, the content of TNF-αin B group was increased 96 percent (1.2pg/gprot) in 2 hour. After 6 hour, the content of TNF-αinitiated descent, and achieved normal level.7-NI distinguished inhibited these changes. After injury, the activity of SOD and CAT were lower than normal in 2 hour. Then the activity of SOD and CAT gradually rise, nearly approached to normal. The activity of nNOS and content of NO obviously decreased in C group, compared with B group. Compared with B group, the content of TNF-αsignificantly decreased in C group in 2 hour.5. Effects of 7-NI on pathological change of smoke inhalation lung injury In A group, lung tissue was smooth, bloom and without bleeding point. In B group, lung tissue was moisture, with some bleeding point and flew lots of cystose fluid. Through light microscope, we observed lots of heterophil granulocyte infiltrated in alveolar space. A lot of fluid effused in alveolar space and alveolar interstitium. 7-NI could inhibit these changes.Conclusion:Smoke inhalation can induce rats into stable, long time hypoxemia, and be made into acute lung injury.In smoke inhalation pulmonary injury, 7-NI can advance arterial partial pressure of oxygen, increase the ability of anti-oxidation, lighten lung edema and tissue inflammation, so it have a good protection on smoke inhalation pulmonary injury.