Effects of soybean isoflavones on the energy metabolism of swimming mice / 中国应用生理学杂志

OBJECTIVE@#To establish an animal model for loaded swimming, so as to investigate the energy metabolism effects of soybean isoflavones (SI) on swimming mice.@*METHODS@#Thirty male Kunming mice were randomly divided into three groups:normal control, swimming group, and swimming+SI group. The normal control group mice were fed a basic AIN-93M diet, the SI groups were supplied with soybean isoflavones(4 g/kg).Two weeks later, the mice were forced to swim for an hour,and then all the mice were killed, the samples of blood, liver and muscles of hind were collected.The serum contents of lactic acid(Lac), the activities of lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), creatine kinase (CK) and ATPase were measured.@*RESULTS@#Compared with normal control,the serum content of Lac was significantly improved in the group of the swimming control and SI(<0.05),the activity of LDH in the serum was obviously improved in the group of the swimming control and SI, and the activity of CK and SDH were both significantly improved in the group of the swimming control and SI except the activity of SDH in the liver of the group SI; compared with the swimming control,the serum contents of Lac,the activities of LDH, ATPase, SDH, CK were obviously improved(<0.05).@*CONCLUSIONS@#Soybean isoflavones can improve the energy metabolism,antioxidant capacity of the swimming mice.

Protective effects of histone deacetylase inhibitor on stress-induced myocardial injury in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the protective effects of histone deacetylase inhibitor on stress-induced myocardial injury.</p><p><b>METHODS</b>Healthy male Wistar rats were randomly divided into 3 groups( n = 6), and the stress-induced myocardial injury model was established with chronic restraint stress method. The protective effects of histone deacetylase inhibitor on stress-induced myocardial injury were observed with Trichostatin A (TSA) intervention. Histone acetylation levels in myocardium of rats were detected by Western blot method, spectrophotometry method was used to dynamically determine the activity of rat serum lactate dehydrogenase (LDH), serum creatine kinase isoenzyme-MB (CK-MB) and Caspase 3, and nagar Olsen staining were used to observe the early myocardial damage.</p><p><b>RESULTS</b>Restraint stress could significantly reduce the level of histone acetylation of myocardium in rats, and TSA intervention could inhibit the stress-induced reduction of myocardial levels of histone acetylation. Restraint stress could cause the significant increase of serum LDH activity ( P < 0.05), serum CK-MB activity ( P < 0.05), and the Caspase 3 activity of myocardial tissue (P < 0.05), and early myocardial damage also occurred during restraint stress. ISA intervention could significantly reduce the serum LDH activity (P < 0.05), the serum CK-MB activity (P < 0.05), the activity of myocardial tissue caspase 3 induced by restraint stress (P < 0.05), and the stress-induced myocardial injury was also attenuated by TSA intervention.</p><p><b>CONCLUSION</b>The histone deacetylase inhibitor TSA can protect stress-induced myocardial injury.</p>

The physiological effects of resveratrol and its potential application in high altitude medicine / 中国应用生理学杂志

Resveratrol, as a natural polyphenolic compound, has a wide range of beneficial effects, which includes anti-tumor, cardiovascular protection, anti-oxidant and estrogen-like effects, and so on. Its various physiological properties are closely related to the therapeutic principle for prevention and treatment of high altitude hypoxia injury. Resveratrol may play an important role in relieving or curing high altitude diseases, especially high altitude polycythemia(HAPC). However, the literature about study and application of resveratrol in plateau medicine field is rarely reported up to now. In this review, we summarized the physiological effects of resveratrol, discussed the possible main principle of resveratrol for HAPC therapy, and looked forward to resveratrol's perspective or potential application in high altitude medicine.

A rat model of high altitude polycythemia rapidly established by hypobaric hypoxia exposure / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of simple hypobaric hypoxia on parameters of hematology and blood rheology in order to establish a rat model of simulated high altitude polycythemia (HAPC) for the study of pathophysiologic mechanisms and medical prevention and treatment of HAPC.</p><p><b>METHODS</b>Forty-eight male Wistar rats were randomly divided into three normal control groups and three hypoxia model groups. Normal control group rats were bred in normoxia conditions, and hypoxia group rats were subjected to hypoxic exposure for 8 hours per day at simulated 5 500 m high altitude in a hypobaric chamber. After hypoxic exposure for 2, 4, 12 weeks, one group of normal control and hypoxia model rats were killed and blood was collected, respectively. Then parameters of erythrocyte and blood rheology were examined.</p><p><b>RESULTS</b>Mucous membrane of hypoxia model rats showed obviously cyanosis after 2 weeks hypoxic exposure. Hemoglobin concentration of hypoxia model rats were beyond 210 g/L after 2 weeks, 4 weeks and 12 weeks hypoxia exposure and significantly increased than that of normal control rats respectively. Besides, RBC counts, hematocrit, whole blood viscosity, erythrocyte aggregation index of hypoxia model rats were all notably higher than those of normal control rats respectively.</p><p><b>CONCLUSION</b>A rat model of high altitude polycythemia can be rapidly established by hypobaric hypoxia exposure at simulated 5 500 m high altitude for 8 hours daily.</p>

Genome-wide association study of high altitude pulmonary edema / 中国应用生理学杂志

<p><b>OBJECTIVE</b>High altitue pulmonary edema (HAPE) impacts seriously people's health at high altitude. Screening of susceptibility genes for HAPE will be used for the evaluation and protection of susceptible people.</p><p><b>METHODS</b>We performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 23 HAPE patients and 17 healthy controls. GO and Pathway analysis softwares were used to analyze and draw gene network.</p><p><b>RESULTS</b>Thirty-nine SNPs were found to be significantly different between case and control groups (P < 10(-4)). GO and Pathway analysis of 27 genes around the 39 SNPs indicated that these genes mainly participate in the regulating of cell proliferation, regulation of nitrogen compound metabolic process and G-protein coupled receptor protein signaling pathway and so on.</p><p><b>CONCLUSION</b>It suggests that these SNPs and genes found in this study may be associated with the susceptibility of HAPE.</p>

The construction and application of a novel apparatus for detecting oxygen consumption of mice under normobaric hypoxia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To establish a method for real-time recording the oxygen consumption of mice under normobaric hypoxia.</p><p><b>METHODS</b>The experimental apparatus was made up of animal container, filling water control system, electronic balance, hose, a computer with weight recording software, etc. The working principle was that the oxygen consumed by animal was replaced by water filling which was controlled by the pneumatic and hydraulic actuator. The water was weighted by an electronic balance and the weight signal was recorded into excel file at the same time. The accuracy and precision of the apparatus were detected by a 10 ml syringe. The oxygen consumption characteristics of 6 acute repetitive hypoxia mice and 6 normal mice were observed.</p><p><b>RESULTS</b>The P value for the paired t test was 1 and the CV value was 4%. The survival time and total oxygen consumption of acute repetitive hypoxia mice were both significantly increased compared to normal mice (P < 0.05), which were (58.8 +/- 6.8) min and (46.0 +/- 8.7) min respectively for the survival time and (85.1 +/- 8.5) ml and (73.6 +/- 5.4) ml respectively for total oxygen consumption.</p><p><b>CONCLUSION</b>The hypoxia tolerance of the acute repetitive hypoxia mice can significantly improved by taking more oxygen in the animal cabin. The accuracy and precision of the apparatus are high and it can be used for the determination of oxygen consumption in hypoxia research.</p>

The selective dilatation effects of iptakalim on pulmonary arterioles in hypoxic pulmonary hypertensive rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the selective dilatation effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener, on pulmonary arterioles in hypoxic pulmonary hypertensive rat.</p><p><b>METHODS</b>SD male rats were divided into 3 groups, control group, the rest were fed in hypoxic and normobaric environment (O2 10% +/- 0.5%, 8 h/d and 6 d/week) and divided into hypoxia group and hypoxia plus acetazolamide (Acz) group (hypoxic rats were treated with ig acetazolamide (Acz) 80 mg x kg(-1) d(-1)) . After 12 weeks, pulmonary arteriole rings about (197 +/- 4) microm were isolated and the tension of hypoxic pulmonary arterioles pre-contracted by 6 nmol/L endothelin-1 (FT-1) was observed with wire myograph system model (DMT 610 m). The relaxing response of hypoxic pulmonary arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine.</p><p><b>RESULTS</b>10(-5) mol/L acetylcholine (ACh)-mediated vasodilatation was greatly reduced in the hypoxic group than those in control group (P < 0.01) and there was no significant difference between Acz treatment group and control group (P > 0.05). Ipt at the concentration ranging from 10(-11) mol/L to 10(-4) mol/L, caused dose dependent vasodilation on both hypoxic pulmonary arterioles and Acz treatment group (P > 0.05), but not on normal group.</p><p><b>CONCLUSION</b>The endothelial function of pulmonary arterioles was damaged under hypoxic pulmonary hypertensive state, and Ipt showed selective dilatation effects on hypoxic pulmonary arterioles. Acz could improve the dysfunction of endothelial cells induced by hypoxic pulmonary hypertensive state, which didn't affect the selective dilatation effects of Ipt on hypoxic pulmonary arterioles.</p>

Proteomic identification of human serum biomarkers associated with high altitude pulmonary edema / 中国应用生理学杂志

<p><b>OBJECTIVE</b>High altitude pulmonary edema (HAPE), a life-threatening disease, has no biological markers used for the routine prevention, diagnosis and treatment. The aim of this study was to identify serum proteins differentially expressed in patients with HAPE for discovering essential biomarkers.</p><p><b>METHODS</b>A complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting. Finally, two most significantly changed proteins were validated by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Eight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins, namely alpha 1-antitrypsin(alpha1-AT), Haptoglobin(Hp), apolipoprotein A-1 (apoA-1) and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV (apoA-IV) decreased significantly. The variation of alpha1-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis.</p><p><b>CONCLUSIONS</b>It is well known that Hp, alpha1-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Therefore, the significant expression changes of Hp, alpha1-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE.</p>

The study of plasma proteomic changes in a patient with high-altitude cerebral edema / 中国应用生理学杂志

<p><b>OBJECTIVE</b>High-altitude cerebral edema (HACE) is one of the most serious acute mountain sickness and its underlying mechanism is still unknown clearly. The aim of this study was to determine the changes of plasma proteins in high altitude cerebral edema patients for discovering essential biomarkers used for the routine prophylaxis, diagnosis and treatment.</p><p><b>METHODS</b>Plasma protein profiling two dimensional gel electrophoresis followed by mass spectrometry was used to explore protein alterations in one patient with high-altitude cerebral edema (HACE). Striking differences in two-dimensional gel proteomes of plasma were observed between high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) and between high-altitude cerebral edema (HACE) and mild acute mountain sickness (mAMS). Furthermore, apolipoprotein E altered in high-altitude cerebral edema was validated by ELISA.</p><p><b>RESULTS</b>Different six spots were found in this study from the comparison between HACE and HAPE, and there were different six spots which were detected from the plasma of HACE patient in comparison to mAMS. Apolipoprotein E was identified in the two groups of comparative maps and results of ELISA consisted with the results of 2-DE.</p><p><b>CONCLUSION</b>In this study, we used proteomic approach to explore HACE firstly and found different proteins that were probably associated with HACE. This would offer a clue to a better understanding of HACE for precaution, diagnosis and treatment.</p>

Apparatus for the measurement of the oxygen uptake of rats subjected to hypobaric hypoxia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To construct an apparatus for the oxygen uptake measurement of rats exposed to hypobaric hypoxia at different simulated altitude.</p><p><b>METHODS</b>The capacity of this apparatus was about 0.01 m3. It included animal experimental cabin, reference cabin, altimeter, altitude vertical velocity indicator, pressure difference inductor and oxygen compensator, low scale manometer, soda lime and calcium chloride, small fan, thermometer, circulating water system and vacuum pump. The oxygen uptake of the rats at 6 000 m, 4 000 m and 1 000 m simulated altitude was measured using this apparatus.</p><p><b>RESULTS</b>The oxygen uptake of the rats at 50 m, 4 000 m and 6 000 m simulated altitude was (24.4 +/- 2.1), (10.8 +/- 2.0) and (8.8 +/- 1.6) ml O2/(kg x min) respectively (average +/- s, n = 10). The oxygen uptake decreased as altitude increased.</p><p><b>CONCLUSION</b>This apparatus can be used to measure the oxygen uptake of the rats at different simulated altitude.</p>

Effect of overexpression of Smad7 gene on cell proliferation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of overexpression of Smad7 gene on cell proliferation in human bronchial epithelial cell lines.</p><p><b>METHODS</b>Human bronchial epithelial cell lines, BEP2D and BERP35T2 cells, were cotransfected with the mammalian expression vectors PCISmad7.neo and pMyc-SEAP, the latter was ac-myc cis-acting enhancer element fused with alkaline phosphatase (SEAP) reporter gene. Expression of c-myc, p15 and p21 mRNA was detected by RT-PCR before and after stable transfection of Smad7 into BEP2D and BERP35T2 cells in order to study the regulation of TGF-beta-mediated growth inhibition.</p><p><b>RESULTS</b>After BEP2D and BERP35T2 cells transfected with Smad7, the transcriptional activity of c-myc was significantly increased. Smad7 overexpressing cells showed upregulation of c-myc expression and downregulation of p15 and p21 expression, which contributed to the loss of TGF-beta responses in these cells.</p><p><b>CONCLUSION</b>Overexpression of Smad7 may facilitate cell proliferation by antagonizing TGF-beta-mediated antiproliferative gene responses.</p>