RESUMEN
OBJECTIVE: To explore the protective effects of hypercapnia on acute lung injury (ALI) and the possible mechanisms. METHODS: Twenty-four healthy New Zealand white rabbits were involved in this study, and randomly divided to three groups, a control group, a therapeutic group, and a prophylactic group (n=8, each). Lipopolysaccharide (1 mg/kg) was injected intravenously to establish the ALI model. Blood gas analysis and artery pressure were monitored. IL-8 and TNF-alpha in the serum and bronchoalveolar lavage fluid (BALF), wet weight/dry weigh (W/D), index of quantitative assessment of histological lung injury (IQA), myeloperoxidase (MPO) and malondialdehyde (MDA) activity in the lung tissue were measured. Apoptosis index of neutrophils were determined. RESULTS: (1) The mean artery pressure, heart rate, PaCO2, and PaO2/FiO2 changed in the ALI model of the therapeutic group and the prophylactic group [(79+/-6) mm Hg (1 mm Hg=0.133 kPa), (180+/-10)/min, (99+/-13) mm Hg, 250+/-26, (80+/-9) mm Hg, (181+/-12)/min, (95+/-11) mm Hg, 241+/-56, respectively]. In the control group, they were (66+/-10) mm Hg, (139+/-13)/min, (31+/-4) mm Hg, 182+/-35, respectively. The differences were significant compared with the control group (t=4.05, 26.32, 5.36, 28.15, 12.54, 11.07, 16.13, 12.36, P<0.05, 0.01). (2) The levels of W/D, MPO, and MDA in the therapeutic group and the prophylactic group were 1.98+/-0.28, 1.87+/-0.30, (6.1+/-1.6) U/g, (5.8+/-1.5) U/g, (20+/-5) mg/L, (19+/-4) mg/L; while in the control group, they were [2.43+/-0.26, (9.0+/-1.3) U/g, (36+/-8) mg/L] respectively. The difference was significant (t=11.07, 24.46, 2.35, 9.63, 12.34, 25.32, P<0.05, 0.01). (3) The levels of IL-8 and TNF-alpha in the serum and BALF and the apoptosis index in the three groups were (50+/-8) ng/ml, (103+/-49) ng/ml, (94+/-16) ng/ml, (44+/-9) ng/ml, (38+/-9)%, (56+/-5)%, (49+/-7) ng/ml, (96+/-50) ng/ml, (91+/-14) ng/ml, (39+/-6) ng/ml, (39+/-10)%, (55+/-10)%, (91+/-43) ng/ml, (177+/-60) ng/ml, (162+/-15) ng/ml, (67+/-7) ng/ml, (19+/-7)%, (43+/-7)%, respectively. The difference was significant among the three groups (t=7.12, 5.55, 7.30, 3.93, 13.08, 8.00, P<0.05, 0.01 respectively). (4) The apoptosis index of neutrophils was negatively correlated with the levels of IL-8 in the serum and BALF (r=-0.73, -0.72, -0.52, -0.64, -0.73, -0.56, all P<0.05), and the levels of TNF-alpha in the serum and BALF (r=-0.57, -0.78, -0.69, -0.75, -0.82, -0.84, all P<0.05). CONCLUSION: Hypercapnia does not affect hemodynamics and has protective effects on ALI.
Asunto(s)
Lesión Pulmonar Aguda/fisiopatología , Hipercapnia/fisiopatología , Pulmón/fisiopatología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Animales , Apoptosis , Líquido del Lavado Bronquioalveolar/citología , Modelos Animales de Enfermedad , Femenino , Hemodinámica , Hipercapnia/sangre , Hipercapnia/metabolismo , Interleucina-8/sangre , Lipopolisacáridos , Pulmón/metabolismo , Masculino , Malondialdehído/metabolismo , Peroxidasa/metabolismo , Conejos , Distribución Aleatoria , Pruebas de Función Respiratoria , Volumen de Ventilación PulmonarRESUMEN
OBJECTIVE: To investigate the effects of interleukin-27 (IL-27) and its receptor (WSX-1) on the proliferation, transformation and collagen synthesis of the mouse lung fibroblasts. METHODS: Cultured mouse lung fibroblasts were treated with TGF-ß1, recombinant murine IL-27, a IL-27 receptor (IL-27R) overexpression vector IL-27R/pCDNA3.1, IL-27 and IL-27R, or all the 3 combined. MTT assay was used to assess the proliferation of the cells, and RT-PCR and Western blotting were employed to examine the mRNA and protein expressions of a-smooth muscle actin (α-SMA) and types I and III collagen; immunofluorescence assay was used to test the expression and location of α-SMA. RESULTS: TGF-ß1 promoted the cell proliferation and obviously enhanced α-SMA expression and types I and III collagen synthesis in the fibroblasts. Both IL-27 and IL-27R significantly inhibited the proliferation of the pulmonary fibroblasts and obviously decreased their α-SMA expression and types I and III collagen synthesis, but when combined,they produced no obvious inhibitory effect on TGF-1-induced proliferation and transformation of pulmonary fibroblasts. CONCLUSION: Both IL-27 and IL-27R alone can suppress the proliferation, transformation, and collagen synthesis of mouse pulmonary fibroblasts, but their combined treatment produces no such inhibitory effect because of the neutralization of exogenous IL-27 by IL-27R to result in the failure of activating the cell signaling pathways.
Asunto(s)
Fibroblastos/efectos de los fármacos , Interleucinas/farmacología , Receptores de Citocinas/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Actinas/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Fibroblastos/citología , Pulmón/citología , Ratones , ARN Mensajero , Receptores de Interleucina , Proteínas Recombinantes/farmacología , Transducción de SeñalRESUMEN
OBJECTIVE: To investigate the effect of intravenous bone marrow-derived mesenchymal stem cell (MSC) transplantation for early intervention of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: Thirty-six mice were randomized into control group, PBS-treated ALI group, and MSC-treated ALI group. In the latter two groups, mouse models of ALI were established by intranasal instillation of LPS, and 1 h later, the 4th passage of MSCs isolated from the bone marrow of mice or PBS were administered via the tail vein. The histological findings, lung wet/dry (W/D) weight ratio, neutrophil count and protein and cytokine contents in the bronchoalveolar lavage fluid (BALF), and myeloperoxidase (MPO) level in the lung tissue were analyzed at 24 h after MSC administration. Engraftment of MSCs in the recipient lung was determined by fluorescent PKH26 staining and flow cytometry. RESULTS: Compared with the control group, PBS-treated ALI group showed significantly higher protein levels, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and neutrophil count in the BALF and MPO content in the lung tissue, with also severe damage of lung histology. MSCs administration significantly reduced the lung W/D weight ratio, the levels of protein, TNF-α, IL-6 and neutrophil count in the BALF and MPO content in the lung tissue, and obviously lessened the lung injury 24 h after the transplantation. MSC administration also significantly increased the level of IL-10 in the BALF. CONCLUSION: Intravenous MSC transplantation can effectively improve the lung histology, attenuate the inflammatory response, reduce pulmonary edema in the early stage of LPS-induced ALI in mice, and such effects are independent of MSC engraftment in the lungs.