| Objectives1. To assess the feasibility of intraperitoneal injection with perfluorocarbon and examine it's prevention effects on acute lung injury.2. To assess the feasibility of intravenous injection with perfluorocarbon emulsion and examine it's prevention effects on acute lung injury.3. To study the mechanism of intravenous injection with perfluorocarbon emulsion on preventing acute lung injury.Methods1. 60 Wistar rats were randomly divided into Normal control-group (NC-group),Normal saline -group (NS-group), C6F14-group, C8F18-group, C10F22-group and safety evaluation-group (SE-group), NS-group and PFC-group were intraperitoneal injection(IP) with 15ml/kg NS or PFC, then general health state, peritoneal cavity absorptivity, blood PFC concentration, arterial blood-gas analysis, histological examination of lung, liver and kidney were carried out at 24h,48h,72h after IP.2. 63 Wistar rats were randomly divided into NC-group , LPS-group and C8F18-group, NC-group were killed at 2h after anesthesia, LPS-group and C8F18-group were treated with normal saline or C8F18 15ml/kg intraperitoneally 48h before injury, Rats were injured by intravenous injection with 7ml/kg LPS, the extent of lung injury was assessed by PaO2 level, histological examination, right lung wet weight/ body weight, tumor necrosis factor-alpha (TNF-alpha) level in serum and BALF at 2 hour, 4hour, 6hour after injury.3. 35 Wistar rats were randomly divided into NC-group, NPE-group, all the rats were intravenous injection with 10ml/kg normal saline or NPE, then general health state, blood PFC concentration , arterial blood gas analysis, GPT, GOT, BUN, CR, histological examination of lung, liver and kidney were observed at2h,4h,6h,24h,48h,10d after IV.4. 53 Wistar rats were randomly divided into NC-group, LPS-group and NPE-group, NC-group were killed at 2h after 1 Oml/kg normal saline (NS) IV, LPS-group and NPE-group were treated with NS or NPE IV 10 min before injury, rats were injured by intravenous injection with 7ml/kg LPS, the extent of lung injury was assessed by PaC>2 level, histological examination, IL-ip level in serum and BALF at 2h, 4h, 6h after injury.5. 24 rats were randomly divided into three groups: Normal control group (NC), LPS-group, NPE-group. NC-group were killed at 6h after 1 Oml/kg normal saline (NS) IV, LPS-group and NPE-group were treated with NS or NPE IV 10 min before injury, rats were injured by intravenous injection with 8ml/kg LPS, the extent of lung injury was assessed by arterial blood gas analysis, lung wet/dry weight ratio (W/D), lung permeability index (LPI) and histological examination at 6h after injury. At the same time, AQP1 protein and mRNA expression in the lung tissue were analyzed by immunohistochemistry and RT-PCR.6. 24 rats were randomly divided into three groups: Normal control group, LPS-group, NPE-group. NC-group were killed at 6h after 1 Oml/kg normal saline (NS) IV, LPS-group and NPE-group were treated with NS or NPE IV 10 min before injury, rats were injured by intravenous injection with 8ml/kg LPS, the extent of lung injury was assessed by arterial blood gas analysis, lung wet/dry weight ratio (W/D), lung permeability index (LPI) and histological examination at 6h after injury. At the same time, ocENaC protein and a,p\yENaC mRNA expression in the lung tissue were analyzed by immunohistochemistry and RT-PCR.Results1. Rats of C6F14-group died at 10h-12h after IP, peritoneal cavity absorptivity and blood PFC concentration of C8F18 and C10F22 group was 66% ^0.75±0.13ug/ml and 58°/cn 0.36±0.04ug/ml at 48h after IP. There were no difference between C8F18-group and C10F22-group in PaC>2 and histological examination of lung, liver and kidney before and after IP.2. PaC-2 in LPS-group and PFC- group was 78.7±4.6mmHg, 76.8±6.7 mraHg,65.7±3.2 mmHg and 76.2±3.2 mmHg, 78.3±7.6 mmHg, 68.9±6.9 mmHg at 2h, 4h, 6h after injured, There were no difference between LPS-group and PFC- group in histological examination and PaC>2 (P>0.05 ) , compared with LPS-group, TNF-alpha level in BALF decreased in C8F18-group at 6h after injured apparently (PO.05).3. All the rats were in good health state after NPE intravenous injection, GPT and GOT were 198.2±10.5u/ml,163.8±12.7u/ml,149.7±18.9u/ml,134.8±16.4u/ml and 272.7±18.6u/mk 234.6±13.7u/mk 232.1±16.9u/mk 219.4±20.3 u/ml in NPE-group at 2h,4h,6h,24h after IV, they were all higher than NC-group (P<0.05). There were no difference between NPE-group and NC-group in GOT and GPT at lOd after IV. Blood PFC concentration was 20±1.8 mg/mU .8±0.7mg/ml,l .5±0.6mg/ml,l .2±0.4mg/ml,0.5±0.2 mg/ml,0.2±0.03 mg/ml ,0mg/ml in NPE-group at 5min,2h,4h,6h,24h,48h,10d after IV, PaO2 of NPE-group (119.2±8.6 mmHg) was higher than NC-group (99.6±4.7mmHg) at 2h (PO.05).4. PaO2 was 96.0±5.2 mmUg, 89.9±4.7 mmHg, 75.7±6.6 mmHg in NPE-group at 2 h, 4h, 6h after injury, they were all higher than LPS-group apparently (P<0.05). Lung pathological grade in NPE-group (8.32±1.77) was lower than LPS-group (11.62±1.38) apparently (PO.05). Compared with LPS-group, IL-ip level of BALF in NPE-group decreased apparently at 4h and 6 h after injury.5. W/D, LPI were 7.86±0.67, 0.345±0.053 and 5.96±0.42. 0.217±0.060 in LPS-group and NPE-group, they were all higher than NC-group (4.12±0.33, 0.028±0.007) (P<0.05). Compared with NC-group, AQPl protein and mRNA expression in LPS-group decreased significantly (PO.05), while AQPl protein and mRNA expression in NPE-group were higher than LPS-group (PO.05).6. W/D. LPI were 7.86±0.67. 0.345±0.053 and 5.96±0.42, 0.217±0.060 in LPS-group and NPE-group, they were all higher than NC-group (4.12±0.33s 0.028±0.007) (PO.05). Compared with NC-group, aENaC protein and ctPyENaC mRNA expression in LPS-group decreased significantly (PO.05), while aENaC protein and ctPyENaC expression in NPE-group was higher thanLPS-group(P<0.05). Conclusions1. C6F14 can't used by intraperitoneal injection for it's higher vapor pressure, intraperitoneal injection with C8F^ C10F22 was a safe administration route, but intraperitoneally administered C8F18 (15ml/kg) can't attenuate pathological injury and improve PaC>2 in rats with ALI.2. Intravenous injection with NPE (lOml/kg) caused a short time liver function injury, but recovered at lOd after IV, NPE had no influence on pathology of lung, liver, and renal. Intravenous injection with NPE could attenuate lung pathological injury and improve PaC>2 in rats with ALI.3. Compared with LPS-group, NPE could improve the PaC>2 level, reduce W/D, t LPI and relieve the lung edema. Compared with NC-group, AQPl and ENaC expression in LPS-group decreased significantly, while AQPl and ENaC expression in NPE-group were higher than LPS-group. All these indicated NPE may have beneficial effects on preventing ALI by regulating AQPl and ENaC expression in the lung tissue.
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