模拟失重时肺动脉反应性变化的内皮机制研究

目的 研究血管内皮在模拟失重时肺动脉反应性变化中的作用.方法 32只雄性Wistar大鼠随机分为尾悬吊组和对照组,采用尾悬吊模拟失重大鼠模型模拟微重力效应,制备离体肺动脉环测定其对几种血管活性物质的反应性变化,经去内皮处理后再测定其对血管活性物质的反应性变化,并进行分析比较.结果 与对照组相比,14天尾悬吊模拟失重大鼠肺动脉环对KCl(68mmol/L)和苯肾上腺素(10-7～10-5mmol/L)的收缩反应性明显下降,对乙酰胆碱(10-8～10-6mmol/L)的舒张反应性明显增强.而去内皮处理后,肺动脉环对苯肾上腺素的收缩反应性恢复,对硝普钠的舒张反应性无明显变化.结论 模拟失重引起肺动脉血管内皮结构或功能改变,是导致其血管发生反应性变化的重要原因.     

一氧化氮样松弛因子缺乏时大鼠心血管的病理生理变化

为探讨一氧化氮样松弛因子缺乏对松弛因子缺乏时心血管系统的病理生理变化及其意义，给大鼠应用ＮＯ合成酶竞争性抑制剂左旋硝基精氨酸，发现血压升高，心率减慢，心脏重量增加，心功能增强，血管环对收缩物质反应性加强，对舒张物质反应性减弱，ＮＯ样松弛因子的效应产物组织ｃＧＭＰ活性明显减低，血浆部分血管活性物质：内皮素升高，血管紧张素Ⅱ，肾素活性降低，病理显示肾入球小动脉内皮细胞增生，内膜增厚，内膜五玻璃样变性。     

连接蛋白37,40,43在失血性休克大鼠肠系膜上动脉中的表达变化及其意义

目的 连接蛋白(Cx)37,40,43在失血性休克大鼠肠系膜上动脉(SMA)中的表达变化及其意义.方法 取休克后不同时相点的SD大鼠SMA,运用RT-PCR和Western blot检测Cx 37,40,43的表达变化;运用反义寡脱氧核苷酸(AODN)转染技术检测Cx 40,43对SMA反应性的影响.结果 Cx 37,40在休克后表达逐渐下降,休克后2 h表达最低,休克后3,4 h表达逐渐升高;Cx43在休克后即刻表达迅速降低,以后进行性表达升高,在休克后2 h达最高点,休克3,4 h表达再次降低;Cx加AODN可以增加血管环内膜依赖性的收缩和舒张反应;Cx 43 AODN可以抑制血管环的收缩和舒张反应.结论 Cx 40和Cx 43参与了失血性休克后内膜依赖的血管舒缩反应性的调节.Cx加具有抑制休克后内膜依赖的血管舒缩反应性的作用;Cx 43具有促进休克后内膜依赖的血管舒缩反应性的作用.     

模拟失重对大鼠肺动脉反应性的影响及其机制研究

目的研究模拟失重对肺动脉反应性的影响及其机制。方法采用-30°尾悬吊14d大鼠失重模型模拟微重力生理效应,利用离体灌流技术测量对照组和尾悬吊14d组大鼠肺动脉环对苯肾上腺素(PE)、氯化钾(KCl)和乙酰胆碱(Ach)等血管活性物质的反应性及Nω-硝基-L-精氨酸甲酯(L-NAME)对肺动脉收缩反应的影响,免疫印迹分析两组肺动脉内皮型一氧化氮合酶(eNOS)的表达。结果与对照组相比,尾悬吊组对PE和KCl的收缩反应显著下降,对Ach的舒张反应明显增强;L-NAME处理后使尾悬吊组对PE的收缩反应恢复;尾悬吊组大鼠肺动脉组织eNOS表达显著高于对照组。结论模拟失重后肺动脉收缩反应下降,舒张反应增强,肺动脉内皮细胞eNOS表达增加以致舒张产物NO增加是肺动脉收缩反应性下降的主要原因。     

血管紧张素Ⅱ 1型受体阻断对模拟失重大鼠动脉血管反应性的影响

目的探讨血管紧张素Ⅱ1型受体(AT1)阻断对模拟失重大鼠动脉血管收缩以及舒张反应性的影响。方法32只SD大鼠随机等分为对照组(CON),模拟失重组(SUS),对照 氯沙坦(losartan)组(CON L),模拟失重 氯沙坦组(SUS L),采用尾部悬吊大鼠模型模拟失重的生理影响,其中CON L组以及SUS L按照30mg.kg-1.day-1的剂量给予氯沙坦干预。3周后,采用离体动脉血管环技术观察大脑基底动脉和股动脉血管环对氯化钾(KCl)、5-羟色胺(5-HT)、苯肾上腺素(PE)、乙酰胆碱(Ach)、硝普钠(SNP)的反应性,以判断动脉血管的收缩以及舒张反应性的变化。结果SUS组大鼠基底动脉对KCl和5-羟色胺收缩最大反应性增强(KCl:F=14.018,P<0.01;5-HT:F=27.435,P<0.01),Ach内皮依赖性舒张最大反应性下降(F=49.045,P<0.01),股动脉对KCl以及苯肾上腺素收缩反应性与对Ach的舒张反应性均下降(KCl:F=19.244,P<0.01;PE:F=19.037,P<0.01;Ach:F=44.973,P<0.01)。SUS L组大鼠基底动脉收缩高反应性以及Ach舒张低反应性均得到改善(收缩:F=14.018,P<0.01;舒张:F=49.045,P<0.01),而氯沙坦干预对股动脉收缩以及舒张反应性并没有影响。结论局部肾素-血管紧张素系统(L-RAS)参与了模拟失重大鼠动脉血管功能重建过程,前半身与后半身动脉血管组织L-RAS差异性激活可能是模拟失重所导致的动脉血管功能分化性改变的重要因素之一。     

模拟失重对离体大鼠肺动脉血管调节功能的影响

目的 研究模拟失重对离体大鼠肺血管调节功能的影响,旨在探讨模拟失重对肺循环的影响和立位耐力降低的发生机制. 方法采用尾部悬吊(TS)大鼠模拟失重生理效应.24只健康雄性Wistar大鼠随机分为对照组、TS 7 d和TS 14 d共3组.采用离体肺灌流技术,利用Power-lab生理系统记录恒流下大鼠肺循环灌注压的变化,并分别于苯肾上腺素(PE)、乙酰胆碱(Ach)和硝普钠(SNP)药物干预后,观察离体肺血管反应性,并计算出肺血管阻力. 结果与对照组相比,TS7 d和TS 14 d大鼠离体肺在恒流灌注下肺动脉压明显降低(F=3.58～20.86,P<0.05或P<0.01),离体大鼠肺动脉血管对PE的收缩反应明显下降,对Ach和SNP的舒张反应明显增强,同时肺血管阻力也相应降低(F=3.56～20.44,P<0.05或P<0.01). 结论尾吊大鼠离体肺血管灌注压降低,血管收缩反应性降低、舒张反应性增强,肺血管阻力减弱,尾吊模拟失重大鼠肺循环血管调节功能减弱,对失重后立位耐力不良有一定的影响.     

肌内皮缝隙连接对失血性休克大鼠血管舒张反应的影响

目的研究肌内皮缝隙连接对失血性休克大鼠内皮依赖和非依赖血管舒张反应的影响。方法56只SD大鼠随机分为硝普钠（SNP）组和乙酰胆碱（Ach）组，每组又分别分为正常对照组、休克0、0．5、1、2、3、4小时7个亚组；各组取其肠系膜上动脉（SMA）制成血管环，分别测量血管环在加18ct一甘草次酸（18α-GA，肌内皮缝隙连接的特异性阻断剂）前、后对SNP和Ach反应性的变化。结果 与正常对照组比较，各休克组SMA血管环对低浓度（10^-9、10^-8、10^-7mol／L）SNP诱导的舒张反应明显降低；对高浓度（10^-6mol／L）SNP诱导的舒张反应无明显变化；18α-GA对SNP诱导的SMA血管环的舒张反应无明显影响。休克后SMA血管环对Ach的反应呈现先下降——后增加——再下降的趋势，即休克前30分钟，SMA血管环对Ach的反应性下降，30分钟后呈上升趋势，至2小时达高峰，随后又再次下降。18α-GA可以拮抗Ach诱导的舒张反应，改变SMA血管环对Ach反应性先下降——后增加——再下降的趋势，使各休克组对Ach的反应性趋于一致。结论 失血性休克后，除内皮依赖性血管舒张反应有短时间的代偿性回升外，其余的内皮依赖性和内皮非依赖性血管舒张反应在休克后均明显降低。肌内皮缝隙连接在休克后内皮依赖性血管舒张反应的变化中起重要调节作用。     

Alteration of Vasoreactivity of Mesenteric Arteries in Rats after Two-Week Simulated Weightlessness

为观察模拟失重对肠系膜动脉血管反应性的影响，采用尾部悬吊大鼠模型模拟失重，并利用离体动脉环测定血管反应性的变化。结果显示：悬吊２周大鼠肠系膜前动脉环对ＫＣｌ（１０～８０ｍｍｏｌ／Ｌ）与苯肾上腺素（１０－１０～１０－４ｍｏｌ／Ｌ）的收缩反应明显降低，对硝普钠（１０－１０～１０－４ｍｏｌ／Ｌ）的舒张反应无明显改变。提示：尾部悬吊明显降低了大鼠肠系膜动脉的收缩能力，而对动脉平滑肌的舒张能力无明显影响     

尾部悬吊大鼠肺动脉和胸主动脉血管反应性及一氧化氮合酶抑制剂的影响

目的进一步明确大小循环动脉对模拟微重力(simulated microgravity,SM)适应机理,阐明SM后立位耐力降低机理,为SM后立位耐力降低寻找新的对抗措施。方法一30。尾部悬吊(TS)大鼠模拟微重力的生理效应。尾部悬吊7d(TS7d)和14d(TSl4d)后的肺动脉(PA)和胸主动脉(TA)环对68mmol／LKCl、累加浓度的苯肾上腺素(PE)和乙酰胆碱(ACh)的反应性作了观察。加入10^-5mol／LNOS抑制剂N-硝基-L-精氨酸甲酯(N-nitro-L-arginine methylester,L-NAME)孵育20min后重复检测对PE的收缩反应和ACh的舒张反应。结果TS7d、TSl4d大鼠PA和TA对KCl及PE的收缩反应非常显著降低;TS7d大鼠PA和TA对ACh的舒张反应显著或非常显著增强,TS14d大鼠PA无变化,TS14dTA仅有增强趋势。加入10^-5mol／L L-NAME后TS7d、TS14d大鼠PA对PE的收缩反应3组无差异,TS7d、TS14d大鼠TA对PE的收缩反应仍有降低;TS7dPA对ACh的舒张反应显著或非常显著降低,其余无变化。结论TS大鼠PA和TA收缩反应的降低可能归因于内皮舒张功能的增强。10^-5mol／LL-NAME可逆转TS后大鼠PA和部分逆转TA的收缩反应降低的实事表明其对内皮细胞的舒张功能有抑制作用．可用于抑制立位耐力降低。     

两周模拟失重大鼠肠系膜动脉血管反应性的变化

为观察模拟失重对肠系膜动脉血管反应性的影响，采用尾部悬吊大鼠模型模拟失重，并利用离体动脉环测定血管反应性的变化。结果显示：悬吊２周大鼠肠系膜前动脉环对ＫＣｌ（１０～８０ｍｍｏｌ／Ｌ）与苯肾上腺素（１０＾－１０～１０＾－４ｍｏｌ／Ｌ）的收缩反应明显降低，对硝普钠（１０＾－１０～１０＾－４ｍｏｌ／Ｌ）的舒张反应无明显改变，提示：尾部悬吊明显降低了大鼠肠系膜动脉的收缩能力，而对动脉平滑肌的舒张能力无明显     

Effect of exercise training on metallothionein levels of hypertensive rats

PURPOSE: Because oxidative stress may be involved in arterial hypertension by affecting the balance between relaxing and contracting factors of vascular smooth muscle, the training-induced adaptation of antioxidant defenses could be implicated in the antihypertensive effect of chronic exercise. It has been suggested that metallothionein (MT), a metal-binding protein, plays an antioxidant role in mammals. The aim of this experiment was to study whether chronic exercise (swimming) influences both the development of arterial hypertension in spontaneously hypertensive rats (SHR) and the modification of MT levels. METHOD: Male SHR and Wistar Kyoto (WKY) rats as control were trained to swim 1 h.d-1 5 d.wk-1 for 8 wk and sacrificed 72 h after the last exercise period. MT and total thiol levels were then measured. RESULTS: Exercise training 1) reduced systolic blood pressure and heart rate in both SHR WKY rats, and 2) was associated with a decrease in hepatic and cardiac MT levels; there was an increase in the aortic MT amounts in exercised SHR only. No modifications were noted in the gastrocnemius muscle or kidneys. In exercised animals, total thiols were lower in the liver but not in kidneys. CONCLUSION: Chronic exercise induced a reduction in arterial hypertension development in SHR rats and an adaptation of the MT levels in cardiac, hepatic, and aortic tissues. Further experiments are needed to pinpoint the role of the MT in these two cases in which oxidative stress occurs.     

Exercise-induced changes in c-Fos protein levels in skeletal muscle of trained and untrained rats

We investigated the effect of an acute bout of endurance exercise on c-Fos protein levels in the extensor digitorum longus muscle of trained and untrained rats. Fifty rats were equally divided into a trained and an untrained group. Rats of the trained group ran on a treadmill 45 min/day for 5 days. On the sixth day, 5 rats were killed without exercise, while the remaining 20 ran as above and were killed 0, 3, 6, and 12 h post-exercise (5 rats at each time point). In the untrained group, 5 rats were killed without exercise, while the remaining 20 ran as above only once and were killed at the same time points as the trained group. Western blotting demonstrated no significant changes in c-Fos protein levels in the untrained group. On the contrary, in the trained group, there was a significant increase at 6 and 12 h compared to 3 h post-exercise. The levels of the protein in the trained rats were above the corresponding levels in the untrained ones at all time points, although these differences reached statistical significance only immediately, 6 h and 12 h post-exercise. These results show that trained skeletal muscle exhibits increased levels of c-Fos, probably as a cumulative result of changes occurring during recovery from each exercise bout, and greater c-Fos response after acute endurance exercise compared to untrained skeletal muscle.     

Exercise training and response to stress: insights from an animal model

The effect of training on the sympathoadrenal and cardiovascular responses to stress was examined in borderline hypertensive rats (BHRs). Animals trained with swimming showed reduced heart rates and plasma norepinephrine and epinephrine levels in response to novel foot shock stress. In contrast, systolic blood pressure was significantly higher in trained BHRs during the stress. Parasympathetic blockade with atropine sulfate (1 mg.kg-1 IV) had little effect on heart rate during stress in untrained rats but significantly elevated the stress-induced heart rate of trained animals. The reduction in stress reactivity produced by exercise training is not manifested in all physiological variables and increases in parasympathetic tone contribute strongly to the attenuated reactivity in heart rate.     

Influence of endurance training on plasma amino acid concentrations in humans at rest and after intense exercise

The influence of exercise training on plasma amino acid concentrations at rest and after exercise was examined in a highly trained group of humans and compared with the response of a control group of nontrained healthy humans. After a bout of intense exercise at the same relative work load, the trained group exhibited significantly (28%) higher plasma concentrations of alanine compared with the nontrained group (nontrained = 313.4 microM, trained = 401.3 microM). Other differences in plasma amino acid concentrations after exercise were related to initial differences present at rest before exercise. At rest, the trained group exhibited significantly higher plasma concentrations of leucine, isoleucine, and tyrosine. Post-exercise ammonia and lactate levels were not significantly different between the two groups when any pre-exercise differences were statistically accounted for. Alanine plays a central role as a primary gluconeogenic substrate and as an ammonia carrier. Therefore, in light of the results presented here, we propose that the higher alanine levels observed in the endurance-trained athletes after exercise may play a physiologically relevant role in accommodation to the metabolic demands of exercise.     

Metabolic and blood catecholamine responses to exercise during alkalosis

The effects of metabolic alkalosis on muscle lactate accumulation and plasma catecholamine concentrations were studied in six highly trained subjects during short-term ergocycle exercises to exhaustion (375 W). The studies were performed after oral administration of NaHCO3 (alkalosis) and CaCO3 (placebo). There was a significant increase in resting blood pH after NaHCO3 ingestion (7.35 +/- 0.02) compared to placebo (7.27 +/- 0.02). A longer endurance time was achieved during alkalosis (75.3 +/- 8 s) than during control (61.5 +/- 2 s), but similar blood pH and HCO3- levels were found at exhaustion in both treatments. Metabolic alkalosis resulted in higher elevation in muscle lactate concentration (31.7 +/- 4.6 mmol.kg-1 wet weight) compared to control (17 +/- 4 mmol.kg-1 wet weight). Despite longer exercise duration in alkalosis, plasma norepinephrine and epinephrine concentrations at exhaustion were reduced by 30 and 34%, respectively. These results indicate that alkalosis increased muscle lactate accumulation during exhaustive exercise. These changes were associated with a reduced blood catecholamine response to exercise.     

Exercise and vasorelaxing effects of CO-releasing molecules in hypertensive rats

PURPOSE: Because carbon monoxide (CO) has been reported able to induce relaxation, we aimed to investigate the effects of exercise training on the rat thoracic aorta responsiveness to a CO-releasing molecule (CORM), tricarbonyldichlororuthenium ([Ru(CO)3Cl2]2). METHODS: Male Wistar rats (N = 32) were divided in hypertensive and normotensive groups using the two-kidney, one-clip model of Goldblatt or SHAM surgery. Hypertensive and normotensive groups were assigned to an exercise training protocol on a level treadmill over a 10-wk period or were assigned to remain sedentary. After the exercise training protocol, blood pressure and cardiac tissue weight were assessed. The responsiveness of endothelium-denuded thoracic aortic rings to [Ru(CO)3Cl2]2 was evaluated by isometric contractions recordings. RESULTS: Systolic, diastolic, and mean blood pressures were significantly increased in hypertensive rats compared with control rats. Exercise training did not significantly alter blood pressure but decreased pulse pressure in hypertensive animals compared with sedentary hypertensive rats. In all groups, application of [Ru(CO)3Cl2]2 induced relaxation in precontracted aortic rings. Compared with normotensive rats, CO-induced relaxation was significantly decreased in hypertensive rats. Nevertheless, training exercise increased relaxation markedly in response to [Ru(CO)3Cl2]2 application in hypertensive rats, whereas it remained without effect in control rings. Pretreatment with TEA, a nonselective K+ channel inhibitor, decreased [Ru(CO)3Cl2]2-induced relaxation in all groups that became similar. In trained hypertensive rats, iberiotoxin had effects similar to those of TEA. CONCLUSIONS: This finding supports the concept that the CORM [Ru(CO)3Cl2]2 can induce relaxation in both normotensive and hypertensive rats with an impairment of the CO-induced relaxation during hypertension. However, exercise training improves the aorta's ability to relax in response to [Ru(CO)3Cl2]2 during hypertension, probably by increasing K+ channel activity.     

Cyclic AMP regulation of fuel metabolism during exercise: regulation of adipose tissue lipolysis during exercise

Adipocytes from trained rats release more free fatty acids in response to hormonal challenge compared to fat cells from sedentary rats. Lipolysis results from increased triglyceride hydrolysis that is catalyzed by a hormone-sensitive lipase, which, in turn, is activated by a phosphorylation mechanism involving cyclic AMP-dependent protein kinase. Cyclic AMP levels within the fat cell are regulated by beta-adrenergic receptor/adenylate cyclase interactions and cyclic AMP phosphodiesterase activity. This review focuses on cyclic AMP regulation of lipolysis in adipocytes from trained and sedentary animals. Although lipolysis is elevated in fat cells from trained rats, no differences are found in beta-adrenergic receptor number or affinity, adenylate cyclase activity, protein kinase activity, or partially purified hormone-sensitive lipase activity when compared to sedentary rats. The major lipolytic alteration induced by exercise training appears to occur at a site distal to hormonal regulation of the beta-adrenergic receptor.     

Effects of resistance training on matrix metalloproteinase-2 activity and biomechanical and physical properties of bone in ovariectomized and intact rats

The purpose of this study was to investigate the influence of resistance training on the activity of matrix metalloproteinase (MMP)-2 and bone biomechanical properties in ovariectomized and intact rats. Forty-eight female rats were divided into two distinct groups, ovariectomized (OVX) and intact (Int), which were subdivided into three similar subgroups: sedentary, acute exercise and chronic exercise. Rats performed a resistance training for 12 weeks in which animals climbed a vertical ladder of 1.1 m with weights attached to their tails. Sessions were performed with an interval of 3, 4-9 and 8-12 days scaled dynamic movements of climbing. Biomechanical and physical analyses were performed using a universal testing machine, and MMP-2 activity analysis by zymography. Bone density (BD), mineral density (MD), maximum load and fracture load was reduced in sedentary and acute exercise OVX groups compared with the sedentary intact group (P<0.05); in contrast, chronically trained groups (OVX and Int) showed a significant increase in BD, MD and fracture load compared with all the other groups. MMP-2 activity in chronically trained groups also showed a significant increase, while the sedentary OVX group showed a decrease in MMP-2 activity compared with the intact sedentary group (P<0.05). Our results suggest that the resistance training proposed in our work was efficient in reverting the deleterious effects of ovariectomy on bone tissue, and also produced modeling effects in intact rats. On the other hand, ovariectomy reduced the activity of MMP-2 and produced deleterious effects on bone tissue, mimicking menopause intrinsically.     

间歇性低氧和运动对高脂饮食诱导胰岛素抵抗大鼠血清内脂素的影响

目的:探讨间歇性低氧和运动对高脂饮食诱导的胰岛素抵抗大鼠血清内脂素的影响。方法:将72只雄性SD大鼠随机分为普通对照组(12只)和高脂造模组(60只),高脂造模组给予高脂饲料。6周末随机取12只高脂造模组大鼠处死,普通对照组同期处死,测试其空腹血糖和胰岛素水平,根据胰岛素抵抗指数(HOMA-IR)确定造模成功后,将其余48只高脂造模组大鼠分为常氧安静组、低氧安静组、常氧运动组和低氧运动组,每组各12只。低氧组暴露在14.5%氧浓度的环境中,4h/d,7d/w;运动组常氧状态下以20m/min进行跑台运动,1h/d,5d/w。4周末,测试各组大鼠血糖、血胰岛素、血清内脂素和内脏脂肪总量等指标。结果:6周高脂饮食后,高脂组大鼠胰岛素抵抗指数显著升高,造模成功。与常氧安静组比较,低氧安静组、常氧运动组胰岛素抵抗指数和血清内脂素均显著下降(P<0.01);低氧运动组血清内脂素较常氧运动组显著升高(P<0.01),与常氧安静组比较无显著性差异(P>0.05)。结论:间歇低氧和有氧运动均可有效改善胰岛素抵抗,并降低血清内脂素水平;而间歇低氧和运动双重作用对血清内脂素的影响不显著。     

牛磺酸对大鼠运动能力的影响

我们以前的研究工作表明，牛磺酸对运动机体可发挥有效的保护作用。为探讨这一保护作用能否提高运动能力，我们观察了分别给予牛磺酸和丙氨酸（可耗竭体内的牛磺酸）后大鼠运动能力和全血粘度的变化。结果发现：运动后大鼠的运动能力较对照组显著增加，牛磺酸使运动大鼠的运动能力进一步增加，而丙氨酸则使运动大鼠的运动能力下降到与对照组无明显差异。给予丙氨酸的运动大鼠，其全血粘度在高、低切变率上都显著增加，给予牛磺酸后，其全血粘度无明显变化，红细胞压积与给予丙氨酸组比较显著降低，与对照组则无差别。以上结果表明：体内牛磺酸对维持运动能力是必需的，外界给予则可使其运动能力进一步增加，这可能与其对血液流变特性的调节有关。