ABSTRACT
Objective To explore the effect of intermittent hypoxia (IH) on RhoA/ROCK pathway in lung and on the muscularization in pulmonary vascular in rat model. Methods Wistar rats (n=40) were randomly divided into two groups:the normal oxygen control group (n=20) and the IH group ( n=20). For 4 weeks, rats in control group and IH group were ex?posed to intermittent normal oxygen (21%O2) or IH (5%-21%O2) respectively. Then, mRNA transcription and protein trans?lation levels of RhoA/ROCK were examined by Real-time PCR and Western blot. Expression of proliferation cell nuclear an?tigen (PCNA) andα-smooth muscle actin (SM-α-actin ) of lung and pulmonary artery were detected by immunohistochemis?try. Results RhoA mRNA transcription level(0.463 ± 0.067 vs 0.182 ± 0.040), ROCK mRNA transcription level(0.384 ± 0.062 vs 0.192 ± 0.052), RhoA protein expression level(0.827 ± 0.065 vs 0.424 ± 0.075)and ROCK protein expression level (0.488±0.088 vs 0.336±0.102)were higher in IH group than those in control group(P<0.05);Levels of PCNA in lung tissue [(54.67±1.80)%vs (9.14±0.91)%], PCNA in pulmonary artery [(49.40±1.21)%vs (8.38±1.13)%], SM-α-actin in lung tis?sue [(42.66±1.63)%vs (35.44±1.41)%] and SM-α-actin in pulmonary artery [(62.62±2.53)%vs (45.54±2.58)%] were also higher in IH group than those in control group(P<0.05). Conclusion Rho/ROCK pathway may play an important role in developing pulmonary hypertension (PH) associated with IH;and IH can promote the muscularization in pulmonary vascular to accelerate PH.
ABSTRACT
Objective To investigate the effect of emphysema and intermittent hypoxia (IH) on the hepatic oxidative stress and inflammatory injury in rats. Methods Sixty male Wistar rats were randomly assigned to 4 groups, control group (A), emphysema group (B), IH group (C) and emphysema+IH group (D). Group A was normally fed. Group B was exposed to smoke, 30 min per time, twice everyday. Group C was exposed to 5%O2 30 s/Air 90 s for 8 h/d. Group D was exposed to smoke twice, about 30 min each time, and exposed 5%O2 30 s/Air 90 s for 8 h/d. After continues exposure for 8 weeks, five rats in each group were randomly selected for arterial blood gas analysis. The tissue blocks of liver was obtained for pathologi-cal scoring and measurements of liver oxidative stress in the rest 10 rats of each group. HE staining was used to calculate the mean lining interval (MLI) and mean alveolar number (MAN). The hepatic inflammatory factor interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) con-centration were measured in four groups. Results Characteristics of emphysema were found in group B and group D. The values of MLI were significantly higher in Group B and group D than those of group A and group C (P<0.05). The values of MAN were significantly lower in group B and group D than those of group A and group C (P<0.05). The levels of SOD and CAT were significantly lower in group B, group C and group D than those of group A (P<0.05). And the levels of SOD and CAT were significantly lower in group D than those of group B and group C (P<0.05). The values of liver MDA were signifi-cantly higher in group B, group C and group D than those of group A, and the values were significantly higher in group D than those of group B and group C (P<0.05). The liver histological scores and the levels of IL-6 and TNF-αwere signifi-cantly higher in group B, group C and group D than those of group A, and the values were significantly higher in group D than those of group B and group C (P<0.05). Conclusion Emphysema and IH have synergistic action in causing hepatic oxidative stress and inflammation.
ABSTRACT
Objective To measure the mRNA expression of immediate-early gene c-fos in endothelial cells by the use of different intermittent hypoxia (IH) protocols. Methods A gas control delivery system was homemade, which pro-duced IH/re-oxygenation(ROX) environmental exposure. The endothelial cells were exposed to IH/ROX cycles, and were di-vided into three groups (A, B and C). There were five sub-groups in each group. Group A included intermittent normoxia group, standard incubator control group, continuous hypoxia group (CH), 1.5%O2 IH group and 10%O2 IH group. There were different frequency IH of 1.5%O2 and 10%O2 sub-groups in group B and group C. Hypoxia time was 15 s. The intermittent hypoxia cycle was 60 and the ROX time was different. The total cycle time was different, including 1.5 h group, 3 h group, 5 h group, 6.5 h group and 9.5 h group. The mRNA expression of immediate-early gene c-fos was measured by real-time PCR. Results There was no significant difference in the level of c-fos mRNA between intermittent normoxia group and CH group. The expression of c-fos mRNA was significantly higher in 1.5%O2 IH group and 10%O2 IH group than that of intermit-tent normoxia group, and there was a higher expression level of c-fos mRNA in 1.5%O2 IH group than that of 10%O2 IH group (P＜0.01). It was found that the mRNA expression of c-fos increased gradually at first, and then gradually decreased. The expression of c-fos mRNA was significantly higher in 5 h group than that of other groups (P＜0.01). Conclusion The mRNA expression of immediate-early gene c-fos is increased after exposing to IH/ROX in endothelial cells, which is closely related with IH extents and frequencies.