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Role of Plateau Hypoxia Hypothermia Complex Damage to the Vascular Endothelial Cells and the Protective Effect

Author: HuangZuo
Tutor: FengHong
School: Tianjin Institute of Physical Education
Course: Human Movement Science
Keywords: hypothermia hypoxia hypoxia hypothermia complex vascularendothelial cells diazoxide
CLC: G804.2
Type: Master's thesis
Year: 2013
Downloads: 9
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Abstract


Objective:China’s plateau mountainous area of widely distributed,1/6of the total land areaof more than3000meters high altitudes,and most of them at our borders, theirstrategic significance are very important. The plateau hypoxia hypothermia complexis the main environmental factors that affect human health and operational capacity.Vascular endothelial cells are the body hypoxia, hypothermia injury in the first, themost likely site of injury, endothelial cell dysfunction can directly affect the plateauidiopathic development of the disease, reversal of endothelial cell dysfunction is animportant strategy for prevention and control the plateau environment factors injurydisease. Therefore study the high altitude and hypothermia, hypoxia and complexconditions on endothelial cells and its mechanism of endothelial cells to protect drugsagainst hypoxic damage effects and mechanisms, has important significance.This study through the establishment of plateau hypoxia hypothermia complexdamage overall animal models and in vitro models of endothelial cell injury, andexplore the plateau hypoxia hypothermia complex on vascular endothelial cell injurylaw and mechanisms of action. And then study the ATP-sensitive potassium channelopener——The diazoxide prevention and treatment of the role of vascular endothelialcell injury caused by plateau hypoxia hypothermia complex. This study provide atheoretical basis for the further understanding of the plateau environment damage, andResearch and development of new plateau idiopathic drugs for Disease Control andPrevention to provide a theoretical basis. Methods1. Overall animal studies plateau hypoxia hypothermia complex environmentalfactors endocrine hormones and catecholamines on vascular endothelial cells. Plateauhypoxia hypothermia complex oxygen chamber simulated high altitude environment,Nanjing Jiancheng NO assay kit detection of NO; Shanghai BlueGene ELISA kitsdetect ADR, NADR, ET, expression; the Wuhan Boster ELISA kit detect theexpression of VEGF.(1) ormones in the of plateau hypoxia hypothermia complexeffects of vascular endothelial function and catecholamines. Set the normal controlgroup (0m,25℃), hypoxia hypothermia complex1(3000m,10℃, h hypoxiahypothermia complex2(6000m,10°C), hypoxia hypothermia complex3(6000m,10℃), hypoxia hypothermia complex4(6000m-5℃). intervention in the hypoxiahypothermia complex1hour. Univariate analysis of variance, multivariate analysis ofvariance, factorial analysis of variance, in order to determine whether hypoxiahypothermia environment in experimental animals caused by vascular endothelialfunction and endocrine changes, and determine the altitude and temperature of the theplateau hypothermia and hypoxia composite injury.(2) Plateau hypoxia, hypothermiaand hypoxia hypothermia complex endocrine hormones and catecholamines on ratvascular endothelial function. Respectively set the normal control group (0m,25℃),the plateau hypoxia group (6000m,25℃), the plateau hypothermia group (0m,-5℃),hypoxia hypothermia complex group (6000m-5℃), intervention1hours.Determination of NO, VEGF, ADR, NADR content in the serum of experimentalanimals, ndependent samples T-test, one-way ANOVA, multivariate analysis ofvariance, factorial analysis of variance, To determine the effects of hypoxia,hypothermia and hypoxia hypothermia complex environment vascular endothelialfunction in experimental animals and catecholamine hormone.(3) Time of hypoxiahypothermia complex endocrine hormones on vascular endothelial cell function andcatecholamines. A control group, respectively, hypoxia hypothermia complex group1h (6000m-5℃,1h), a hypoxia hypothermia complex group4h (6000m,-5℃,4h)and hypoxia hypothermia complex8h group (6000m,-5℃,8h). Determination of NO, ET, VEGF, ADR, NADR content in the serum of experimental animals.2. Vitro experiments hypoxia hypothermia complex environmental factors on thevascular endothelial cells. Aortic film adherent culture, to train male Wistar rat aorticvascular endothelial cells in vitro; ADR analog hypothermia environment ofendothelial cells; Nanjing Jiancheng LDH, NO, NOS determination kit to detect thecell culture medium LDH content of NO and NOS; MTT assay endothelial cellsurvival; flow cytometry apoptosis of endothelial cells; Shanghai BlueGene ELISA kitfor detection of VEGF, ET, HIF1-a expression. The research altitude hypoxia onvascular endothelial cells, Set the Control (21%O2,37℃),Hypoxia24h (1%O2,37℃,24h), Hypoxia25h(1%O2,37℃,25h). Hypoxia27h(1%O2,37℃,27h). Researchadrenaline (ADR) analog low-temperature environment and composite low-oxygenenvironment on endothelial cells, set the normal control group (serum-free M199medium, normal culture) the ADR1group (ADR final concentration of0.1mmol/L),the ADR2group (ADR a final concentration of0.01mmol/L), ADR3group (ADRfinal concentration0.001mmol/L). Independent samples T-test, one-way ANOVA,clarify the difference between hypothermia and hypoxia composite damage with asingle environmental factors damage, Make sure that the hypothermia and hypoxiacomposite role of endothelial cells to cause injury mechanisms.3. Diazoxide altitude hypoxia, hypothermia and its complex environmentalfactors vascular endothelial cell injury in rats. role of Diazoxide in the prevention andtreatment of hypoxia-induced endothelial cell injury. Set the normal control group,hypoxia two diazoxide group (diazoxide final concentration of0.1mmol/L inserum-free M199medium and endothelial cells placed in the hypoxia incubatorhypoxic exposure27h), hypoxia diazoxide+5-HD group (diazoxide and5-HD finalconcentration of0.1mmol/L in serum-free M199medium and endothelial cells inhypoxia incubator the hypoxia exposed to27h). Diazoxide factors of hypoxichypothermia induced endothelial cell injury in rats. Set the normal control group,hypoxia ADR+diazoxide group (ADR and diazoxide final concentration of0.1mmol/L in serum-free M199medium and endothelial cells in the hypoxic incubator hypoxic exposure27h), hypoxiaADR+diazoxide+5-HD group (ADR, nitroustriazine,5-HD final concentration of0.1mmol/L serum-free M199medium withendothelial cells exposed to hypoxia in hypoxia incubator27h). Independent samplesT-test, one-way ANOVA, Proved the protective effect of diazoxide endothelial cellinjury caused by hypoxia and hypothermia and hypoxia composite factors.Results1. Hormones in the of altitude hypoxia hypothermia The combined effects ofvascular endothelial function and catecholamines. Respectively, at an altitude of3000m,6000M when observed at different temperatures (10℃,-5℃) on serum NO,ADR impact. Compared with the control group,3000m above sea level,10℃environment exposure, serum NO show a downward trend (P>0.05),3000m above sealevel,-5°C environment can cause the levels of NO decreased significantly (P <0.05).Compared with the control group,3000m10℃and3000m-5℃environmentalinterventions ADR content of the serum was significantly higher (P <0.01). At analtitude of6000m,10℃environment serum NO, ADR content did not changesignificantly. Compared with the control group, the altitude of6000m,-5℃environment Serum NO release significantly reduced (P <0.01), the release of ADRwas significantly higher (P <0.01). Multi-factor analysis of variance showed, Altitudehad no significant effect on serum NO and ADR (P <0.05), altitude and temperatureinteraction (P>0.05), temperature has a significant effect on serum NO and ADR nosignificant effect on NO, but produce a significant effect on ADR (P <0.05).Plateauhypoxia, hypothermia and hypoxia hypothermia complex endocrine hormones andcatecholamines on rat vascular endothelial function. Were observed altitude of6000mand hypothermia-5℃and composite effect on serum NO, VEGF, ADR, NADRimpact. Compared with the control group, the high-altitude hypoxia group (6000m,25℃,1h) Serum NO content was significantly lower (P <0.05), and the release ofVEGF was significantly higher (P <0.05), ADR, NADR The release was increased, no statistically significant difference. Compared with the control group, the coldtemperature group (0m,-5℃,1h) NO release in rats decreased, no statisticallysignificant difference; release of VEGF was significantly higher (P <0.01), ADRtheNADR release was significantly higher (P <0.01). Compared with the control group,hypoxia and hypothermia (6000m-5℃,1h) composite NO content decreasedsignificantly (P <0.01); the VEGF, ADR, NADR expression was significantly higher(P <0.01). Altitude on NO, VEGF, ADR have a significant effect (P <0.05),Temperature on ADR, NADR all have a significant impact (P <0.05), height andtemperature interaction of NO, NADR no significant impact (P <0.05) but on VEGF,ADR (P<0.05). Plateau hypoxia, hypothermia and hypoxia hypothermia complexeffect of hormone effects on endothelial cell function and catecholamines. Comparedwith the control group, hypoxia and hypothermia composite intervention1h,4h, ratNO release significantly decreased (P <0.01). Levels of VEGF1h group (P <0.01),4hgroup (P <0.05) was significantly higher,8h groups was not statistically significantdifference.4h ET was significantly increased (P <0.05), no statistically significantdifference between the1H group and8h group.1h,4h group ADR, NADR releasewas significantly higher (P <0.01).2. Vitro hypoxia and hypothermia environment on vascular endothelial celldamage. The rat aortic endothelial cells which were cultured by the method of aorticexplants adherent were identified by CD31immunofluorescence, its positive rate wasabove96%.27h in1%O2hypoxic environment may promote vascular endothelialcells (P <0.01) increase in LDH levels, cell viability, NO, NOS content decreasedsignificantly (P <0.01), VEGF, ET, HIF1a, expression increased (P <0.01), increasedapoptosis. ADR concentration of0.1mmol/L (P <0.01) increase in LDH content maypromote vascular endothelial cells, cell viability decreased significantly (P <0.01),VEGF, ET HIF1a-expression increased (P <0.01), and increased apoptosis. ADRconcentration of0.1mmol/L intervention endothelial cells cultured in theenvironment of hypoxia (1%O2) for27h, the LDH content was found to increase (P<0.01), and decreased cell survival (P <0.01) the content of NO decreased (P <0.01), the content of NOS show a downward trend, VEGF, ET, HIF1a expression increased(P <0.01), increased apoptosis (P <0.01).3. Diazoxide induced vascular endothelial cell injury prevention and treatment ofhypoxia and hypoxia hypothermia role. A final concentration of0.1mmol/Ldiazoxide intervention endothelial cells cultured in1%O2hypoxia27h, nostatistically significant difference compared with the control group; LDH decreasedsignificantly compared with the hypoxia group(P <0.01), the cell survival rate wassignificantly higher (P <0.01), NO, NOS release increased significantly (P <0.01),VEGF, ET expression decreased (P <0.01), and apoptosis was also significantlyreduced (p <0.01). A final concentration of0.1mmol/L diazoxide and ADRintervention endothelial cells cultured in1%O2hypoxia for27h, LDH decreasedsignificantly compared with the hypoxia group (P <0.01), the cell survival rate wassignificantly higher(P <0.01), VEGF, ET the decreased expression (P <0.01), andapoptosis was also significantly lower (P <0.01); NO, NOS’s release was significantlyreduced (P <0.01), the expression of HIF1a increased (P<0.01).Conclusion1. Hormones in the of altitude hypoxia hypothermia The combined effects ofvascular endothelial function and catecholamines. Respectively,6000m above sealevel-5℃altitude hypoxia hypothermia environment can lead to reduced vascularendothelial function in experimental animals and catecholamine hormone rise;Compared with the more complex environment, the complex environment of6000m10°C on endothelial function and catecholamine hormones reduced. The resultssuggest that hypoxia and hypothermia composite environment catecholaminesendocrine hormone increased impact on vascular endothelial function, vascularendothelial damage can cause hypoxia interaction. Multi-factor analysis of varianceand factorial analysis of variance, in the lower altitude (3000m), high temperature(10℃) environment, Altitude and temperature as well as the complex role ofendothelial cell damage is not significant, However, with increasing altitude (6000m) and the decrease of temperature (-5℃), Altitude and temperature, as well as thecomposite action of the additive effect caused serious damage to the endothelial cellsoccurs. Hypoxic environment can significantly reduce the vascular endothelialfunction. The low-temperature environment can significantly cause endocrinedysfunction in experimental animals.6000m-5°C hypoxia and hypothermiacomposite environment can significantly affect the the experimental animalsendothelial function and catecholamines endocrine hormonal changes, Experimentalanimals and cause vascular endothelial hypothermia and hypoxia composite damage.Endocrine hormone changes of catecholamines in the complex environment ofhypothermia and hypoxia is an important factor causing endothelial damage, andenables and to exacerbate vascular endothelial serious injury. Hypothermia andhypoxia composite environment intervention4hours rat vascular endothelial cells inacute hypothermia and hypoxia can cause multiple lesions.2. Altitude hypoxia exposure can damage the vascular endothelial cells; ADRanalog low-temperature exposure on vascular endothelial cells damage; compositeaction of the two can lead to vascular endothelial cell injury.3. Diazoxide can improve vascular endothelial cell injury caused by hypoxia; toimprove hypoxia composite ADR caused by vascular endothelial cell injury.In summary, this study found that, Plateau hypoxia and hypothermia compositerole has a special law on the role of vascular endothelial cell damage, both compositeaction with increasing altitude, the temperature drops rendering the overlay effect;The diazoxide prevention and treatment of the hypoxic hypothermia compositeenvironmental factors vascular endothelial cell injury caused by.

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