Objective To observe the effects of exogenous pulmonary surfactant (PS) on ventilation-induced lung injury (VILI) in rats, and to investigate its possible mechanisms. Methods A total of 40 Wistar rats were divided into 4 groups with randomized blocks method: control group, high tidal volume (HV) group, VILI group, and PS group, with 10 rats in each group. The control group was subjected to identical surgical procedure but was never ventilated. After 30 min of mechanical ventilation (MV) with Vt 45 ml/kg, the rats in HV group were killed immediately; rats in the VILI group were continually ventilated for up to 150 min with Vt 16 ml/kg; in the PS group, 100 mg/kg of PS administered intratracheally and with the same settings as VILI group. Mean artery pressure (MAP), blood gas analysis, lung wet to dry weight ratios (W/D), thorax-lung compliance, and cell counts in bronchoalveolar lavage fluid (BALF) were determined. Nuclear factor-κB(NF-κB) activity in lungs was measured by enzyme-linked immunosorbent assay (ELISA), interleukin-8(IL-8) in serum and BALF was determined by radioimmunoassay (RIA). Pathological examination of the lung was performed. Results Injurious ventilation significantly decreased MAP and PaO2/FiO2, but increased NF-κB activity and W/D. MAP and PaO2/FiO2 improved, but NF-κB activity, IL-8 in serum and BALF, and cell counts in BALF reduced significantly in PS group compared with those in VILI group. Histological studies showed reduced pulmonary edema and atelectasis in the PS group. Conclusion PS administered intratracheally can suppress the increased activity of NF-κB induced by VILI, exogenous PS can be used to treat VILI.
ObjectiveTo estimate whether alpha 1-antitrypsin (AAT) can reduce ventilator-induced lung injury (VILI) in acute respiratory distress syndrome (ARDS) rats after mechanical ventilation.MethodsThe rats were randomly divided into 3 groups: a sham (S) group, a mechanical ventilation (V) group and a mechanical ventilation/AAT (VA) group. The rats in the S group only received anesthesia, and the rats in the V and VA groups received endotoxin to simulate ARDS followed by mechanical ventilation for 4 hours. At the beginning of ventilation, the rats in the V group received saline, and the rats in the VA group received AAT. The PaO2/FiO2 ratio and the lung wet/dry (W/D) weight ratio were tested. The total protein and neutrophil elastase concentrations and the neutrophil and macrophage counts in bronchoalveolar lavage fluid (BALF) were tested. Proinflammatory factors in BALF and intercellular cell adhesion molecule-1 (ICAM-1) and microphage inflammatoryprotein-2 (MIP-2) in the serum were also detected. Furthermore, the oxidative stress response was detected, and histological injury and apoptosis were evaluated.ResultsCompared with the S group, PaO2/FiO2 was significantly decreased in the V group and the VA group, the protein concentration in the BALF and the lung W/D weight ratio were significantly increased, the concentration of inflammatory factors in BALF and peripheral blood was significantly increased, and inflammatory cells in BALF also increased. Meanwhile, malondialdehyde (MDA) concentration, myeloperoxidase (MPO) and nicotinamide adeninedinucleotide phosphate (NADPH) activity increased significantly. The V group and VA group were severely damaged, and the number of apoptotic cells increased significantly. Compared with the V group, the PaO2/FiO2 in the VA group significantly increased; the W/D weight ratio and the BALF protein concentration decreased; the number of macrophages and neutrophils in the BALF, and the concentration of elastase significantly decreased; tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in BALF decreased, IL-10 increased; ICAM-1 and MIP-2 in peripheral blood decreased. At the same time, the MDA concentration, MPO and NADPH activities in the VA group were significantly lower than those in the V group; the tissue damage was significantly reduced, and the number of apoptosis was significantly reduced. In addition, compared with the V group, the expression of Bax, gelsolin and cleaved caspase-3 decreased in the VA group, but the expression of Bcl-2 was increased (all P<0.05).ConclusionsAAT can relieve VILI in ARDS rats. The protection conferred by AAT may be associated with the anti-inflammatory, antioxidative stress response and antiapoptotic effect of AAT.
Lung injury could be classified as acute and chronic injuries, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. Lung function recovery mainly depends on inflammation adjusting, lung and airway remodeling, endogenous stem cell proliferation and differentiation, and tissue repair. The principles of clinical therapy include inhibition of inflammation, balancing coagulation and fibrinolysis, and protective lung ventilation for acute lung injury; while reduction of hyper-secretion, bronchodilation, adjusting airway mucosal inflammation and immunity, as well as improving airway remodeling for chronic obstructive pulmonary disease. The functional recovery of lung and airway depends on endogenous stem cell proliferation and repair. The purpose of clinical treatment is to provide assistance for lung and airway repair besides pathophysiological improvement.
Objective To explore the protective effects of liver X receptor-αactivator ( LXRα)T0901317 on rats with acute lung injury ( ALI) . Methods Seventy-two male Wistar rats were randomly divided into three goups, ie. a control group, a LPS group, and a T0901317 group. Artery blood gas analysis,lung tissue wet/dry weight ratio,myeloperoxidase activity, and lung histopathological changes were measured.The expressions of LXRαand TNF-αmRNA in lung tissue were detected by RT-PCR. The protein levels ofTNF-αand LXRαwere examined with ELISA and immunohistochemistry, respectively. Results In the ALI rats, PaO2 decreased, lung W/D weight ratio and myeloperoxidase activity increased significantly compared with the control group ( P lt; 0. 05) . Histopathological examination also revealed obvious lung injury. In theLPS group, the expression of TNF-αmRNA in lung tissue and the level of TNF-αprotein in lung homogenate and serum increased markedly( all P lt; 0. 05) while the expression of LXR-αmRNA declined significantly ( P lt; 0. 05) . Immunohistochemical staining showed that lung tissues of the normal rats expressed LXRαsignificantly but in the LPS group the expression of TNF-αand LXR-αin lung tissue decreased markedly ( P lt;0. 05) . After the treatment with T0901317, the expressions of LXR-αin lung tissues were significantly higher than those in the LPS group both at the mRNA and the protein level ( P lt; 0. 05) . Conclusion T0901317 plays an anti-inflammatory effect through up-regulating the expression of LXR-αand suppressing the expression of TNF-α, thus reduces the infiltration and aggregation of inflammatory cells in lung tissue.
Objective To assess the efficacy of ambroxol on acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods The randomized controlled study involving ambroxol on ALI/ARDS were searched and identified from Cochrane Library, PubMed, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, WanFang Resource Database, and Chinese Journal Fulltext Database. The quality of the chosen randomized controlled studies was evaluated, and then the valid data was extracted for meta-analysis. Results Ten articles were included, all in Chinese, including 459 cases ofpatients ( 233 cases in experimental group,226 cases in control group) , with baseline comparability between the various experiments. Systematic review showed that in ALI/ARDS patients, high-dose ambroxol was in favor to improve PaO2 [ WMD =12. 23, 95% ( 9. 62, 14. 84) , P lt; 0. 0001] and PaO2 /FiO2 [ WMD = 32. 75,95% ( 30. 00, 35. 51) , P lt;0. 0001] , reduce lung injury score [ WMD = - 0. 49, 95% ( - 0. 66, - 0. 33) ,P lt;0. 0001] , decrease the duration of mechanical ventilation [ WMD = - 2. 70, 95% ( - 3. 24, - 1. 12) ,P lt;0. 0001] and the length of ICU stay [ WMD= - 2. 70, 95% ( - 3. 37, - 2. 04) , P lt;0. 0001] , and lower mortality [ OR=0. 46,95%( 0. 22, 1. 00) , P = 0. 05] . Conclusions The existing clinical evidence shows that, compared with conventional therapy, high-dose ambroxol plus can significantly improve PaO2 , PaO2 /FiO2 , lung injury score, duration of mechanical ventilation, length of ICU stay and mortality in ALI/ARDS patients. Due to the quality of research and the limitations of the study sample, there likely to exist a bias,and may affect the strength of result, so we expect more high-quality, large-scale randomized controlled clinical trial to verify.
ObjectiveTo investigate the therapeutic effects of different doses of tanshinone ⅡA microemulsion on radioactive lung injury. MethodsSeventy-two Wistar rats were randomly divided into a healthy control group,a model group,a liposome microemulsion treatment group,a tanshinone ⅡA microemulsion high-dose group,a tanshinone ⅡA microemulsion middle-dose group,and a tanshinone ⅡA microemulsion low-dose group.Radiation-induced lung injury model was established by irradiation of radiotherapy instrument.In addition to the control group,other groups received 6MV X radiation with one dosage of 22Gy.Four rats in each group were sacrificed on 7th,14th,and 28th day,respectively.Lung tissues were sampled to analyze the pathological changes by HE staining and the Smad7 mRNA expression by RT-PCR.The level of glutathione(GSH)in peripheral blood was determined by ultraviolet spectrophotometric method. ResultsIn the model group and four treatment groups,lung tissue biopsy showed the pathological changes gradually from pulmonary alveolitis to fibrosis.The level of Smad7 mRNA in lung tissue and GSH in peripheral blood were higher in the high-dose group,the middle-dose group and the low-dose group than those in the model group at all time points(P<0.05),and were highest in the high-dose group.There was no significant differences in the level of Smad7 mRNA in lung tissue and GSH in peripheral blood between the liposome microemulsion treatment group and the middle-dose group. ConclusionTanshinone ⅡA microemulsion has treatment effect on lung injury in a dose dependent manner.
Objective To compare three approaches of lipopolysaccharides ( LPS) administration for inducing acute lung injury ( ALI) in mice. Methods LPS ( 5 mg/kg) was intratracheally aerosol administered ( ITA group) , intratracheally instilled ( ITI group) , or intraperitoneally injected ( IPI group) to induce ALI in BLAB/ c mice. Evans Blue instead of LPS was intratracheally administered to observe the liquid distribution in the lungs. Two hours after LPS administration, the mice were sacrificed and the lungs were removed to determine wet-to-dry lung weight ratio ( W/D) , and the histological changes were evaluated by HE staining. Phosphorylation level of IκB-αand NF-κB p65 in lung tissue were investigated by Western blot. Transcription intensity of TNF-α and IL-1β mRNA in lung tissue were detected by real-time quantitative PCR. Results Evans Blue distributed more uniformly in the ITA group than the ITI group. The lung W/D ratio and histological changes score in three LPS administration groups were all significantly higher than the normal control group ( P lt;0. 01) , with the ITA group being the highest. The phosphorylation levels of IκB-αand NF-κB p65 were significantly higher in the ITA group than the ITI group ( P lt;0. 05) , and were significantly higher in the ITI group than the IPI group ( P lt; 0. 05) . Transcription intensity of TNF-αand IL-1βmRNA was significantly higher in the ITA group than the ITI group ( P lt;0. 05) , and were significantly higher in the ITI group than the IPI group ( P lt;0. 05) . Conclusion Being non-invasive and convenient,intratracheal LPS aerosol inhalation is an optimal method to induce ALI in mice because it induces more extensive and uniformly distributed injuries in lung.
ObjectiveTo investigate the effect of ambroxol hydrochloride on c-Jun N-terminal kinase (JNK) signal pathway in gastric aspiration lung injury. MethodsForty healthy male Sprague Dawley rats were randomly divided into a control group, an injury group, a SP600125 (JNK specific inhibitor) group and an ambroxol group. The model of gastric aspiration lung injury was established by aspiration of gastric contents. The rats in the SP600125 group preoperatively received intravenous injection of JNK specific inhibitor SP600125 (3 mg/100 g). The rats in the ambroxol group received intravenous injection of ambroxol hydrochloride (50 mg/kg) 2 hours after the damage occurred. The neutrophil count and malondialdehyde (MDA) activity in bronchoalveolar lavage fluid (BALF), the lung wet weight/dry weight ratio (W/D), and myeloperoxidase (MPO) activity were measured. The protein expressions of JNK and phosphorylated JNK (p-JNK) and inducible nitric oxide synthase (iNOS) in lung tissue were detected by Western blot method. The changes of lung tissue structure were observed under light microscope. ResultsIn the injury group, the neutrophil counts and MDA activity in BALF, W/D, MPO activity, p-JNK and iNOS protein expression increased significantly, lung tissue appeared obvious histopathological injury compared with the control group. In the SP600125 group and the ambroxol group, neutrophil count and MDA activity in BALF, lung W/D, MPO activity, p-JNK and iNOS protein expression were significantly decreased compared with the injury group (P < 0.05), and the damage of the lung tissue pathology was reduced. The expression of JNK protein in lung tissue was not different in all groups (P > 0.05). ConclusionsJNK is involved in inflammatory reaction of gastric aspiration lung injury. The protective effect of ambroxol may be related to the inhibition of JNK signaling pathway and the inhibition of iNOS expression.
Objective To investigate the effect of aerosolized perfluorocarbon (PFC) (FC77) on gas exchange，histopathological changes of lung in acute lung injury and pulmonary expression of tumor necrosis factor-α (TNF-α) mRNA.Methods After acute lung injury (ALI) was induced by oleic acid (OA)，16 rabbits were assigned randomly into 2 groups,ie.aerosolized perfluorocarbon group (PFC group) and conventional mechanical ventilation group (CMV group).Gas exchange parameters were measured before and after ALI，at 1，2，3，4 h after treatment.Histological sections taken from 6 different parts of lung were stained by hematoxylin and eosion.The express of TNF-α mRNA in the 2 different parts of lung were detected by in situ hybridization (ISH).Results Compared with CMV group，the PaO2 and static lung compliance (CLst) were significantly increased (Plt;0.05)，the histopathological lesions of lung were attenuated，and the TNF-α mRNA expression was decreased significantly in PFC group (all Plt;0.05).There was more expression of TNF-α mRNA in backside than that in foreside of lung in two groups (Plt;0.05).Conclusion Aerosolized perfluorocarbon (PFC) can decrease expression of tumor necrosis factor-α mRNA in the lung，and improve the CLst and oxygenation during acute lung injury.
Objective To review the effects of pulmonary surfactant in adult patients with acute lung injury ( ALI) /acute respiratory distress syndrome ( ARDS) . Methods Randomized controlled trials ( RCTs) were recruited from PubMed ( 1966.1-2011.3) , ISI Web of Knowledge ( all the years) and Wanfang Database ( 1982-2011) . Related published data and attached references were hand searched. All the RCTs about pulmonary surfactant for the adult patients with ALI/ARDS were included, then a meta-analysis was performed. Results Eight eligible trials were enrolled. Pooled analysis showed that treatment with pulmonary surfactant was not associated with reduction in 28 or 30-day mortality compared with the control group [ OR 1.05, 95% CI ( 0.90, 1.22 ) , P = 0.55] , neither did subgroup analysis in the pneumoia/ aspiration, sepsis, and trauma/ surgery induced ALI/ARDS patients. Three RCTs showed the oxygenation was significantly improved in adult ALI/ARDS patients receiving pulmonary surfactant compared with the control group( Plt;0.05) . Shorter mechanical ventilation days was shown in the ALI/ARDS patients receiving pulmonary surfactant in one RCT(Plt;0.05) . Conclusions Meta-analysis showed pulmonary surfactant did not reduce the 28 or 30-day mortality of adult patients with ALI/ARDS, however, improved the oxygenation. Pulmonary surfactant can be considered a therapy in ALI/ARDS.