Effect of iptkalim on myocardial enzymes and free radicals metabolism with hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of iptkalim on myocardial enzymes and free radicals metabolism with hypoxic pulmonary hypertension (HPH), in order to provide evidence for the mechanism of iptkalim on clinical treat.</p><p><b>METHODS</b>110 young men stayed at high altitude above 5 000 m were divided into iptkalim group (n = 74) and placebo group (n = 36), aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malonaldehyde (MDA), nitric oxide(NO) and nitric oxide synthase(NOS) were detected before and after took medicines for 6 mouths.</p><p><b>RESULTS</b>After took medication for 6 mouths, ALT, AST, gamma-GT, CK and LDH were reduced, SOD, NO, and NOS were increased, MDA were reduced, there were very significant difference (P < 0.05).</p><p><b>CONCLUSION</b>Oxygen free radicals have taken part in the process of HPH, iptkalim have the effect of anti-peroxidation of lipid and protect myocardial cells stress injured by hypoxia which related with mitochondrial membrane and cell membrane's K(ATP) channel activation.</p>

Changes of VEGF, TNF-alpha, IL-6 and NO in serum of patients with HAPE / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the possible pathophysiological process and mechanisms underlying the development and formation of high altitude pulmonary edema(HAPE) by observing the changes in contents of VEGF, TNF-alpha, IL-6 and NO in serum from the initiated and recovery of HAPE patients.</p><p><b>METHODS</b>We studied 10 HAPE patients in a Chinese population. The patients were divided into two groups including HAPE initiate group and the recovery group. Contents of VEGF, TNF-alpha, IL-6 and NO in serum of the two groups were determined to study the process of HAPE.</p><p><b>RESULTS</b>VEGF levels in the HAPE initiate one and the recovery groups were (167.9 +/- 26.5 and 53.1 +/- 17.0 pg/ ml), respectively. There was a significant decrease of VEGF content in recovery one compared to the HAPE group. The same results for TNF-alpha were gained. The levels of TNF-alpha in recovery group was much lower than that in the HAPE initiate one. They were (29.2 +/- 6.8) pg/ml and (86.2 +/- 24.1) pg/ml, respectively. The contents of IL-6 in HAPE initiate group and the recovery group were (32.3 +/- 16.5) pg/ml and (12. 5 +/- 8.0) pg/ml, respectively. But no significance existed. The level of NO in HAPE initiate group was (33.8 +/- 3.3) micromol/L, and it remarkably increased to (74.1 +/- 6.2) micromol/L in recovery one.</p><p><b>CONCLUSION</b>VEGF, TNF-alpha, IL-6 and NO participated in the different aspects of the pathophysiological process and might have influence on HAPE.</p>

Effect of neotype carbonic anhydrase target-based inhibitors(P-8) on the hypoxic tolerance in mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of different doses of P-8 in increasing the Hypoxia tolerance of mice and the mechanisms involved.</p><p><b>METHODS</b>The health mice were placed into the oxygen deficit bottles and measured the survival time in the condition of hypoxia. The male mice were put into the ladder cage, then placed them into the hypobaric champer to determine the survival time of mice with decompression hypoxia (min). We observed the activity changes of the mice's organization carbonic anhydrase II (CAII). By using the drug in prophylaxis, we investigated the effects of carbonic anhydrase target-based inhibitors P-8 for improving the hypoxia tolerance.</p><p><b>RESULTS</b>(1) In improving the endurance of mice in the condition of hypoxia, the survival time of 6.25 mg/(kg x d) and more doses of P-8 groups were (27.38 +/- 4.63, 29.53 +/- 4.43, 29.67 +/- 7.28, 31.55 +/- 6.34, 32.45 +/- 6.65, 36.81 +/- 7.24 and 35.41 +/- 4.20) min, compared with the control group (22.90 +/- 3.19) min , the survival time significantly prolonged (P < 0.05, P < 0.01); compared to the same dose of acetazolamide groups (24.54 +/- 3.17, 22.70 +/- 3.04, 22.67 +/- 2.99, 23.93 +/- 0.96, 27.87 +/- 5.06, 30.79 +/- 5.12 and 35.14 +/- 6.46) min, the survival time significantly prolonged; P-8 groups and Acetazolamide's minimum effective dose were 6.25 and 100 mg/(kg x d), the potency of P-8 is 16 times Acetazolamide. (2) In improving the endurance of mice in the condition of hypoxia, the survival time of middle and high doses of P-8 groups [(24.82 +/- -3.92, 28.27 +/- 5.89) min] were significantly longer than those in control group [(21.96 2.51) min, P < 0.05]; compared with the acetazolamide (23.11 +/- 3.71) min, the survival time of high dose of P-8 group was significantly prolonged. (3) Compared with the normal control group, P-8 [(25 mg/(kg x d), 50 mg/(kg x d), 100 mg/(kg x d), 200 mg/(kg x d)] dose groups inhibited the activity of carbonic anhydrase II (CAII) in the renal (P < 0.05, P < 0.01); P-8 [100 mg/(kg x d) and 200 mg/(kg x d)] dose group significantly inhibited the activity of carbonic anhydrase II (CA II) in the brain (P < 0.05).</p><p><b>CONCLUSION</b>P-8 treatment improved the endurance of mice in the condition of hypoxia and worked better than Acetazolamide. The mechanism may be related to the inhibition of carbonic anhydrase organization.</p>

Changes of VEGF and AQPs gene and protein expression in rat brain tissue during hypoxic encephaledema / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the changes of vascular endothelial growth factor(VEGF), aquaporin (AQP) gene and protein expression during hypoxic encephaledema so as to provide the basis for elucidating the brain injury caused by acute hypoxic exposure and pathogenesis of the encephaledema.</p><p><b>METHODS</b>Wistar rats were randomly divided into 4 groups, i.e. control group, hypoxia 4 000 m group, hypoxia 6 000 m group and hypoxia 8 000 m group. Rats in hypoxic groups were exposed to hypoxia at simulated altitude of 4 000 m, 6 000 m and 8 000 m above sea level for 8 hours respectively in order to establish hypoxic encephaledema model. The water content in brain was determined by dry-weight method. The changes in morphology of brains were observed under optical microscope. The changes in expression of VEGF, AQP1 and AQP4 genes and protein were determined by RT-PCR and immunohistochemistry.</p><p><b>RESULTS</b>(1) The results determined by dry-weight method indicated that water content of rats brain increased markedly after rats were exposed to a simulated altitude at 6 000 m, 8 000 m. (2) The results determined by microscopy indicated that during the rats exposed to hypoxia, nerve cells, vascular endothelial cells and astrocyte foot processes swelled lightly, transudate occurred in tissues at 4 000 m. The swelling of vascular endothelial cell (VEC) and astrocyte foot processes aggravated, interspace between vessels and tissues enlarged, and transudate in tissue increased at 6 000 m. The swelling of VEC and astrocyte foot processes went from bad to worse, interspace between vessels and tissues enlarged further, and transudate in tissue increased evidently at 8 000 m. (3) During hypoxic encephaledema, the expression of VEGF, AQP1 and AQP4 mRNA increased, AQP1 was abnormally expressed on the surface of VEC, and the expressive level of VEGF and AQP1 on VEC and AQP4 on astrocyte foot processes increased.</p><p><b>CONCLUSION</b>The changes in expression and distribution of VEGF, AQP1 and AQP4 during encephaledema caused by hypoxic exposure may induce blood-brain barrier injury, and may be one of the pathogenesis of hypoxic encephaledema.</p>

Changes of erythrocyte deformability in rats acclimatized to hypoxia and its molemechanism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the changes of erythrocyte deformability in rats acclimatized to hypoxia and its molemechanism.</p><p><b>METHODS</b>Male rats were randomly divided into three groups (n = 10): normal control group, acute hypoxia group and hypoxia acclimatization group. Animals were exposed to hypoxia for 0, 1, 28 d, blooded from their hearts after anaesthetized, respectively. Erythrocyte deformability, membrane fluidity, cholesterin and total lipid, lipid components of erythrocyte membrane, erythrocyte membrane ATPase and the concentrations of Na+ and Ca2+ were measured respectively. The two-dimensional electrophoresis maps of the rats erythrocyte membrane protein were achieved. The different protein spots were founded by image master 2D elite and identified by mass spectrum.</p><p><b>RESULTS</b>(1) In acute hypoxia group, the deformability, membrane fluidity, the content of membrane cholesterin and total lipid were declined. The content of phosphatidylserines (PS), sphingomyelin (SM) in erythrocyte membrane lipids were increased, phosphatidylcholine (PC) reduced. The activity of ATP enzymes reduced and the concentration of Na+ and Ca2+ in erythrocyte increased. The two-dimensional electrophoresis maps of the rats erythrocyte membrane protein were achieved. Four of the seven protein spots selected increased and three of them showed no change. (2) In hypoxia acclimatization group, the deformability, membrane fluidity, the content of membrane cholesterin and total lipid were increased than those in acute hypoxia group, similar to normal group. The content of PS, SM in erythrocyte membrane lipids were reduced, PC increased. The activity of ATP enzymes induced and the concentration of Na+ and Ca2+ in erythrocyte increased after hypoxia acclimatization. Four of those protein spots mentioned increase and three declined after hypoxia acclimatization. They were respectively proved by mass spectrum to be alexin binding protein, aquaporin chip, membrane inhibitor reactive lysis, phospholipids scramblase, glucose transferase, aminophospholipid translocases, ATP-dependent floppase, the latter three proteins were associate with the overturning of erythrocyte membrane lipids.</p><p><b>CONCLUSION</b>Acute hypoxia caused the corresponding damage of erythrocyte deformability, erythrocyte membrane fluidity, erythrocyte membrane proteins erythrocyte expression, the activity of membrane ATPase and the concentration of Na+ and Ca2+ in erythrocyte. The parameters above were improved after hypoxia acclimatization, so hypoxia acclimatization effected positively in the damage to erythrocyte due to acute hypoxia. The three membrane proteins might play important roles in the deformability improved by hypoxia acclimatization, which included phospholipids scramblase, aminophospholipid translocases and ATP-dependent floppase.</p>

Effect of hypoxia on activation of the peripheral blood T lymphocyte in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effect of hypoxia on the peripheral blood T lymphocyte subsets and co-stimulatory molecules in rats so as to provide the basis for studying the intervention measure.</p><p><b>METHODS</b>Before hypoxia and during hypoxia at 8 000 m for 8 h, 3 d, 6 d and 10 d the change of peripheral blood T lymphocyte subsets and co-stimulatory molecules in rats were detected by flowcytometer with three-color immunofluorescence label.</p><p><b>RESULTS</b>Rats were exposed to hypoxia at 8 000 m for 8 hours, and CD3+, CD8+, CD8+ CD28- lymphocyte percentages were significantly decreased (P < 0.01) compared with that before hypoxia. After 3 days of hypoxia, besides aforesaid change, CD4+ CD28+ lymphocyte percentage also prominently decreased (P < 0.01) and CD4+ CD28- prominently increased (P < 0.01). After 6 and 10 days of hypoxia, CD3+, CD4+ lymphocyte percentages were further decreased, while CD8+ CD28+ lymphocyte percentage significantly increased (P < 0.01).</p><p><b>CONCLUSION</b>After exposed to hypoxia at 8 000 m for 8 hours and 3 days, activation of CD8+ and CD4+ T lymphocyte was prominently decreased, while with the prolong of exposed time activation of CD8+ T lymphocyte was significantly increased.</p>

Study of hypoxia-induced immune injury and its intervention measure / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the characteristic of hypoxia-induced immune injury, its mechanisms and the intervention measure.</p><p><b>METHODS</b>The change of immune organ index, T lymphocyte subsets of peripheral blood and immune organ in mice during hypoxia were detected. Lymphocyte apoptosis of immune organ, pathology of lung and kidney in mice were observed. Then by way of prophylaxis we studied the effect of Chinese Traditional Medicine on hypoxia-induced immune injury in mice.</p><p><b>RESULTS</b>(1) Exposure to hypoxia at 8 000 m simulated altitude for 8 h resulted in marked decrease in CD4+ CD8+ thymocytes and marked increase in CD4+ CD8-, CD4- CD8+ thymocytes (P < 0.01). After 3 days of hypoxia, the mice had a much lower percentage of CD4+ T-cell (P < 0.05). The ratio of CD4+/CD8+ decreased significantly and aforesaid changes of thymocyte were further enlarged. Also mice had a pronounced increase in rates of late apoptosis or necrosis of spleen lymphocyte and thymocyte (P < 0.05). After 6 days of hypoxia, index of spleen was significantly increased (P < 0.05), index of thymus was significantly decreased (P < 0.05) and CD3+, CD4+, CD8+ lymphocyte percentage of spleen were significantly decreased (P < 0.01). Also late apoptosis or necrosis lymphocytes of spleen and thymus were further increased (P < 0.01), viable cell rates of spleen lymphocyte and thymocytes were markedly decreased (P < 0.01), early apoptosis rates of spleen lymphocyte were markedly increased (P < 0.01). There was no significant change in the percentage of CD8+ lymphocyte in peripheral blood during the whole hypoxia period. (2) New Compound Codonopsis Pilosula (NCCP), Xiang Qi Polysaccharide (XQP) and NCCP + XQP could significantly increase the number of peripheral blood CD3+, CD4+ and spleen CD4+, but had no significant influence on the number of spleen CD8+. XQP and XQP+ NCCP could significantly decrease the number of CD4+ CD8+ (P < 0.01), increase that of CD4+ CD8- (P < 0.01), and had no significant influence on CD4- CD8+ in thymus. However, NCCP didn't influence the component of thymocytes.</p><p><b>CONCLUSION</b>After hypoxia at 8 000 m simulated altitude decrease of lymphocyte of periphery in mice may be related with increase of apoptosis and necrosis of lymphocyte, and with increase of distribution of lymphocyte to lung in early period of exposure. NCCP and XQP have hopeful prospect in intervention study of hypoxia-induced immune injury.</p>

Protective effects of new compound codonopsis tablets against acute mountain sickness / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study on the protective effects of new compound codonopsis tablets against acute mountain sickness (AMS).</p><p><b>METHODS</b>Forty-five male plain resident soldiers stayed at 1400 m altitude for 3 months were randomly divided into two groups, control (15 men) and treatment group (30 men). Single blind trial was used in this study. The subjects in the two groups took placebo and new compound codonopsis tablets respectively for 5 days before climbing to high mountain, and continued to take for another 10 days until the 3rd day after arriving at 5200 m altitude. On the 1st , 3rd, and 5th day after they arrived at 5200 m altitude, the score and the degree of AMS symptoms of soldiers were followed up and recorded according to State Military Standard GJB1098-91--"Principles of diagnosis and treatment of benign form of acute mountain sickness", heart rate (beats/min) and arterial oxygen saturation (%) were detenrmined. On the 6th day after they arrived at high altitude, forced vital capacity(FVC), forced expired volume in one second(FEV1.0), FEV1% (FEV1.0/FVC), FEF25%-75%, peak expiratory flow (PEF) and maximal voluntary ventilation (MVV) were detected, total frequency of hands cross movement and memory of order numbers test were measured.</p><p><b>RESULTS</b>Comparison with control, AMS symptoms of treatment group reduced on the 1st, 3rd, and 5th day after arriving at 5200 m high altitude (P < 0.01). The degree of AMS symptoms of treatment group was significantly different from that of control. The proportion of slight symptoms in treatment group was high, and that of relative serious symptoms in control was high. Compared with control, FVC, FEV1.0, FEF25%-75%, PEF and MVV of treatment group increased (P < 0.05, P < 0.01), and Ttis, Ctis of treatment group increased (P < 0.05, P < 0.01), Atime decreased markedly (P < 0.05), there was no statistically significant difference in Etis and Sum between the two groups.</p><p><b>CONCLUSION</b>New compound codonopsis tablets could decrease the incidence of AMS, mitigate the symptoms of AMS, and improve breathing function and fingers movement function. New compound codonopsis tablets have an obvious effect on prevention and treatment of acute mountain sickness.</p>

Current alteration of K(V) channel in SLE patient's peripheral blood lymphocytes and it's significant / 中国应用生理学杂志

<p><b>AIM</b>To observe the property alteration of K(v) channel in SLE patient's peripheral blood lymphocyte and its significant.</p><p><b>METHODS</b>The patch-clamp technique was used to record the current of K(V) channel in SLE patient's peripheral lymphocyte.</p><p><b>RESULTS</b>The current amplitude of K(V) channel in the SLE patient's lymphocytes decreased, it was (258.6 +/- 112.5) pA in healthy people, but in SLE patient it was (139.4 +/- 58.5) pA (P < 0.05). There was no other changes in the property of channel, include activation potential, inactivation property, channel closing kinetics and its pharmacological property.</p><p><b>CONCLUSION</b>The decline of SLE patient's cell immunity may be related to the decrease of the amplitude of K(V) channel current.</p>