RESUMEN
In the present study an experimental high-altitude intestinal barrier injury rat model was established by simulating an acute hypoxia environment, to provide an experimental basis to assess the pathogenesis, prevention and treatment of altitude sickness. A total of 70 healthy male Sprague-Dawley rats were divided into two groups: Control group (group C) and a high-altitude hypoxia group (group H). Following 2 days adaptation, the rats in group H were exposed to a simulated 4,000-m, high-altitude hypoxia environment for 3 days to establish the experimental model. To evaluate the model, bacterial translocation, serum lipopolysaccharide level, pathomorphology, ultrastructure and protein expression in rats were assessed. The results indicate that, compared with group C, the rate of bacterial translocation and the apoptotic index of intestinal epithelial cells were significantly higher in group H (P<0.01). Using a light microscope it was determined that the intestinal mucosa was thinner in group H, there were fewer epithelial cells present and the morphology was irregular. Observations with an electron microscope indicated that the intestinal epithelial cells in group H were injured, the spaces among intestinal villi were wider, the tight junctions among cells were open and lanthanum nitrate granules (from the fixing solution) had diffused into the intestinal mesenchyme. The expression of the tight junction protein occludin was also decreased in group H. Therefore, the methods applied in the present study enabled the establishment of a stable, high-altitude intestinal barrier injury model in rats.
RESUMEN
We conducted a case-control study to investigate the association of mitochondrial DNA (mtDNA) haplogroups with acute mountain sickness (AMS) in Han Chinese from southwestern (SW) China. Pearson's chi-square test or Fisher's exact test revealed significant reduction of mtDNA haplogroups D and M9, while a significant increase of haplogroup M7 in AMS subjects compared with non-AMS subjects. The multivariate logistic regression analysis after adjustment for body mass index (BMI), a risk factor of AMS in the present study, showed that both D and M9 were associated with significantly decreased risk of AMS, while M7 was associated with a significantly increased risk of AMS (OR=0.605, p=0.000; OR=0.037, p=0.001, and OR=2.419, p=0.001, respectively). In addition, further analysis stratified by the AMS severities indicated that haplogroup B was correlated with a 2.41-folds increased risk of developing severe AMS (95%C.I=1.288-4.514, p=0.006). Our findings provide evidence that, in SW Han Chinese, mtDNA haplogroups D and M9 are related to individual tolerance to AMS, while haplogroups M7 and B are risk factors for AMS.
Asunto(s)
Mal de Altura/genética , ADN Mitocondrial/genética , Predisposición Genética a la Enfermedad , Haplotipos , Enfermedad Aguda , Adolescente , Altitud , Mal de Altura/etnología , Pueblo Asiatico/genética , Índice de Masa Corporal , Estudios de Casos y Controles , ADN Mitocondrial/análisis , Humanos , Masculino , Mitocondrias/genética , Especies Reactivas de Oxígeno/metabolismo , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To investigate whether the expression and function of aquaporin-1 (AQP-1) is altered by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in primary rat lung microvessel endothelial cells (LMECs) after exposure to lipopolysaccharide (LPS), and to study the expressions of AQP-1 and AQP-5 in lung tissue of rats with acute lung injury (ALI) induced by LPS. The aim is to further clarify the pathogenesis of ALI/acute respiratory distress syndrome (ARDS). METHODS: (1) In vitro: The third passage LMECs were randomly divided into LPS group, TNF-alpha group, IL-1beta group and DMEM control group, and the experimental groups were exposed to LPS, TNF-alpha and IL-1beta respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to quantify AQP-1 mRNA changes and an immunocytochemistry method was used for determining AQP-1 protein changes in cultured rat LMECs. Isotope tracer technique was applied for the assay of the intra-cellular tritium water ((3)H2O) signal intensity in rat LMECs. (2) In vivo: Forty male Wistar rats were randomly divided into five groups: LPS 2 h group, LPS 4 h group, LPS 6 h group, LPS 8 h group and a control group, eight rats per group; The LPS treated groups served as the ALI models. RT-PCR was used to observe the changes of AQP-1 and AQP-5 mRNA and the immunohistochemistry method was used for determining AQP-1 and AQP-5 protein changes in ALI rats. RESULTS: (1) In vitro: The expression of AQP-1 mRNA and protein in LMECs were decreased significantly in the LPS group (0.428 +/- 0.026, 0.366 +/- 0.009), the TNF-alpha group (0.446 +/- 0.029, 0.374 +/- 0.014) and IL-1beta group (0.454 +/- 0.023, 0.377 +/- 0.007) as compared to the DMEM control group (0.793 +/- 0.035, 0.660 +/- 0.013, respectively; all P < 0.01). The quantities of tritium water's permeability in the LPS group, the TNF-alpha group and the IL-1beta group [(726 +/- 58), (738 +/- 45), (774 +/- 44) counts per minute] were significantly less than that in the DMEM control group [(1 148 +/- 70) counts per minute, P < 0.01]. (2) In vivo: The expression levels of AQP-1 and AQP-5 mRNA in ALI rats (LPS 2 h group 0.409 +/- 0.018, 0.421 +/- 0.020; LPS 4 h group 0.421 +/- 0.023, 0.412 +/- 0.023; LPS 6 h group 0.435 +/- 0.020, 0.388 +/- 0.031; LPS 8 h group 0.438 +/- 0.016, 0.386 +/- 0.019, respectively) were significantly lower than that in the control group (0.794 +/- 0.015, 0.787 +/- 0.022; all P < 0.01). CONCLUSION: AQP-1 and AQP-5 may play a role in abnormal fluid transportation and probably involve in the formation of pulmonary edema in ALI/ARDS.