Effects of chronic intermittent hypobaric hypoxia on immune function in rat / 中国应用生理学杂志

<p><b>AIM</b>To elucidate the effect of CIHH on cellular immunity and humoral immunity in rat by using flow cytometry method, immunohistochemistry method and electron microscopy techniques.</p><p><b>METHODS</b>Forty-eight male adult Sprague-Dawley rats were randomly divided into 4 groups: control(CON) group, 14 days CIHH (CIHH14) group, 28 days CIHH (CIHH28) group, 42 days CIHH (CIHH42) group. The animals in CIHH groups were exposed to 14, 28 and 42 days hypobaric hypoxia(simulated 3 000 m altitude, 5 h per day), respectively. Half of the animals in each group was treated with normaxia and the other half animals were treated with acute hypoxia for 1 h. CD3, CD4, CD8 T lymphocytes, natural killer (NK) cells, IgG, cortisol, epirenamine and C-reactive protein were examined. The weight and ultrastructure of thymus and spleen were observed.</p><p><b>RESULTS</b>(1) Compared with CON, both indexes of thymus and spleen in CIHH14 rats were increased significantly. Spleen index, but not thymus index, was increased in CIHH28 and CIHH42 rats. The thymocytes and spleen cytes in rat were injuryed during acute hypoxia, but the damage in CIHH rats was significant slighter than that in CON rats. (2) Compared with CON, CIHH28 and CIHH42, CD8 in CIHH14 rats were decreased, ratios of CD4/CD8 was increased and NK was decreased. (3) The rats of CON during acute hypoxia showed that CD4 was increased, CD8 was decreased, ratio of CD4/CD8 was elevated, and NK was increased. But there were no significant changes of CD3, CD4, CD8 and NK in CIHH28 and CIHH42 animals during acute hypoxia. (4) Compared with CON, CIHH28 and CIHH42, cortisol in CIHH14 rats was increased obviously, Epirenamine, cortisol and C-reactive protein in CON rats were increased, but there were no obvious changes in CIHH rats before and after acute hypoxia.</p><p><b>CONCLUSION</b>CIHH protects the immune function of rat against acute hypoxia, which is related with the regulation of neuroendocrine.</p>

Effect of chronic intermittent hypobaric hypoxia on α(1)-adrenergic receptor of myocardium participates in the cardioprotection / 生理学报

The purpose of the present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on α(1)-adrenergic receptors and the role of alpha(1)-adrenergic receptors in the protection of CIHH against ischemic injury of myocardium. Sixty-six adult male Sprague-Dawley rats were randomly divided into four groups: control group (Con), 14-day CIHH treatment group (CIHH14), 28-day CIHH treatment group (CIHH28) and 42-day CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia mimicking 5 000 m altitude (p(B)=404 mmHg, p(O(2))=84 mmHg) in a hypobaric chamber, 6 h daily for 14, 28 and 42 d, respectively. Control animals lived in the same environment as CIHH animals except hypoxia exposure. After anesthesia with sodium pentobarbital (3.0-3.5 mL/kg body weight, i.p.), papillary muscle was taken from the right ventricle of rat and perfused with modified Tyrode's solution continuously, at constant temperature (37 °C) and perfusion speed (12 mL/min). Muscle contraction was evoked by electric stimuli. Different concentrations (1x10(-7), 1x10(-6) and 1x10(-5) mol/L) of phenylephrine (PE), an alpha(1)-adrenergic receptor agonist, were applied cumulatively to investigate the effect of PE on the mechanic contraction of right ventricular papillary muscles of rats in Con, CIHH14, CIHH28 and CIHH42 groups. Also, prazosin (1x10(-6) mol/L), an α(1)-adrenergic receptor antagonist, was used to investigate the role of α(1)-adrenergic receptor in the protective effect of CIHH on papillary muscle. The results showed: (1) PE increased the maximal isometric tension (P(max)) and maximal velocity of tension development (P(dT/dt)) of muscle contraction in a dose-dependent manner (P<0.05), and the increase of the muscle contraction was much greater in CIHH28 and CIHH42 rats than that in Con rats (P<0.05). Under 1x10(-5) mol/L of PE, the increases of P(max) and P(dT/dt) over the baseline were 51.2% and 44.5% in CIHH28 group, 48.6% and 44.5% in CIHH42 group, and 28.7% and 24.5% in Con group, respectively; (2) The contraction of papillary muscle decreased during simulated ischemia, but the decrease was slighter in CIHH rats than that in Con rats (P<0.05). The decreases in P(max) and P(dT/dt) were 59.6% and 53.6% in CIHH28 group, 60.4% and 49.9% in CIHH42 group, and 74.4% and 64.7% in Con group, respectively; (3) The protective effect of CIHH on ischemic papillary muscle was abolished by prazosin (1x10(-6) mol/L). The results of the present study suggest that CIHH increases the activity of α(1)-adrenergic receptor, which is possibly one of the mechanisms for the cardioprotection of CIHH.

Protective effect of polydatin against ischemia/reperfusion injury in rat heart / 生理学报

The aim of the present study was to investigate the protective effect of polydatin against myocardial ischemia/reperfusion injury in rats and the underlying mechanism. In anesthetized rats, ischemia and reperfusion arrhythmia produced by ligating and loosing the coronary artery was recorded and myocardial infarct size was measured. In Langendorff isolated rat heart, cardiac function was recorded before and after 30 min of global ischemia followed by 60 min of reperfusion. The parameters of cardiac function include left ventricular developed pressure (LVDP), maximal differentials of LVDP (±LVdp/dt(max)) and coronary flow (CF) were measured. Myocardial superoxide dismutase (SOD) activity, the contents of myocardial malondialdehyde (MDA) and nitric oxide (NO) as well as the activity of nitric oxide synthase (NOS) were measured in isolated heart. The results showed: (1) Arrhythmia score and myocardial infarct size were significantly lower in polydatin group than that in the control group (P<0.05, P<0.01); (2) The recovery of LVDP, ±LVdp/dt(max) and CF during reperfusion in polydatin group were significantly better than that in the control rats (P<0.05, P<0.01); (3) SOD activity in polydatin group was significantly higher than that in the control group, but MDA content was lower in polydatin group than that in the control group (P<0.05); (4) NO content and NOS activity, especially constitutive nitric oxide synthase (cNOS) activity in polydatin group were higher than that in the control group (P<0.05); (5) L-NAME, the NOS inhibitor, reversed the protective effect of polydatin against ischemia/reperfusion injury. The results suggest that polydatin has a protective effect against ischemia/reperfusion injury in rat heart. The cardioprotection of polydatin is mainly mediated by cNOS which leading to an increase in NO production.

Effects of different modes of intermittent hypobaric hypoxia on ischemia/reperfusion injury in developing rat hearts / 生理学报

The aim of the present study was to explore the effects of two different modes of intermittent hypobaric hypoxia (IHH) on myocardial ischemia/reperfusion injury in developing rat hearts. Postnatal male sprague-Dawley rats (n=72) were divided randomly into 3 groups: intermittent hypoxia at 3 000 m (IHH3000) group, intermittent hypoxia at 5 000 m (IHH5000) group and control group. The isolated hearts were perfused in the Langendorff apparatus, undergoing 30 min of global ischemia and 60 min of reperfusion. Cardiac function, coronary flow and lactate dehydrogenase (LDH) activity were recorded at 5 min before ischemia and 1, 5, 10, 20, 30, 60 min during reperfusion, respectively. The heart weight was measured at the end of the experiment. The results showed that: (1) There was no difference in body weight gaining between IHH3000 and control groups. The gain of body weight in IHH5000 group was much lower than that in IHH3000 and control groups (P<0.01). (2) Compared with that in the control group, the recovery of cardiac function in IHH3000 group was enhanced at 60 min after ischemia/reperfusion, coronary flow was increased, and LDH activity was decreased (P<0.05), meaning a cardioprotective effect occurred. There was no significant difference in heart weight between IHH3000 and control groups. In addition, cardiac function restored better in IHH3000 group after 42 d of hypoxic exposure than that after 28 d of hypoxic exposure (P<0.05). (3) Compared with that in the control group, the recovery of cardiac function in IHH5000 group was lower, coronary flow was decreased, and LDH activity was increased (P<0.05). There was a hypertrophy in the right ventricle in IHH5000 group. All changes indicated definitely that a detrimental effect developed in IHH5000 group. The results suggest that proper IHH can protect developing rat hearts against ischemia/reperfusion injury while this effect could be affected by the modes of intermittent hypoxic exposure.