白茅根多糖对小鼠耐缺氧作用的影响

目的观察白茅根多糖(RIP)对小鼠耐缺氧作用的影响,为白茅根的临床应用和药物开发研究提供一定理论依据.方法超声提取RIP.60只小鼠随机分为6组,分别灌胃给予生理盐水、普萘洛尔和不同剂量的RIP,观察小鼠缺氧存活时间和耗氧量.结果灌胃给予RIP 50,100,200,400 mg·kg-1和普萘洛尔20 mg·kg-1,使小鼠0～5 min的耗氧量分别降低2.48%,23.14%,10.74%,5.79%和28.93%,5～10 min的耗氧量分别降低21.13%,16.90%,38.73%和9.86%.灌胃给予氯化钠注射液、普萘洛尔20 mg/kg和RIP 50,100,200,400 mg·kg-1,小鼠缺氧30 min存活率分别为0,0,20%,10%,50%,20%.普萘洛尔组、RIP 200 mg·kg-1和400 mg·kg-1组,小鼠的缺氧存活时间分别延长33.16%,37.31%和35.23%.结论RIP能明显增强实验小鼠的耐缺氧作用.     

胡芦巴总皂苷对脑缺血保护作用

目的　研究胡芦巴总皂苷的抗脑缺血作用 ,并探讨可能的作用机制。方法　采用结扎小鼠双侧颈总动脉造成急性不完全性脑缺血模型 ,观察平均存活时间 ;另取小鼠断颅后测定断颅喘息时间 ;采用玻片法 ,观察胡芦巴总皂苷对凝血时间的影响 ;采用比浊法 ;观察其对体外血小板聚集率的影响 ,并测定全血粘度。结果　胡芦巴总皂苷 40、80、16 0mg·kg-1,延长小鼠平均存活时间 (P <0 0 5 ,P <0 0 1) ,及凝血时间 (P <0 0 1) ,抑制血小板聚集率 (P <0 0 1) ,80 ,16 0mg·kg-1延长断颅小鼠喘息时间 (P <0 0 1)且具剂量依赖性 ;80 ,16 0mg·kg-1在低 ,中切变率能降低兔血粘度 (P <0 0 5 )。结论　提示胡芦巴总皂苷具有抗脑缺血作用     

曲美他嗪对异丙肾上腺素致大鼠心肌损伤的保护作用

目的 :研究曲美他嗪对异丙肾上腺素致大鼠心肌损伤的影响及机制。方法 :用曲美他嗪或普萘洛尔治疗异丙肾上腺素大鼠心肌损伤模型 ,观察心肌组织病理改变 ,测定心肌乳酸 ,丙二醛 ,ATP ,ADP和AMP含量。结果 :曲美他嗪组心肌组织病理分级优于普萘洛尔组 (P <0 .0 1) ,曲美他嗪组心肌乳酸和丙二醛含量分别由 (0 .2 9±s0 .0 3)mol·kg- 1和 (0 .74± 0 .10 )mol·kg- 1降低到 (0 .2 2±0 .0 4 )mol·kg- 1和 (0 .5 6± 0 .0 7)mol·kg- 1(P <0 .0 1) ,ATP含量也由 (2 .0± 0 .3)mmol·kg- 1增加到 (2 .4 7± 0 .18)mmol·kg- 1(P <0 .0 5 ) ,ADP含量由 (1.6± 0 .5 )mmol·kg- 1降低到 (0 .6 4± 0 .19)mmol·g- 1。与异丙肾上腺素组比较有非常显著差异 (P <0 .0 1) ,AMP含量有增加趋势。曲美他嗪组心肌能量代谢得到改善 ,与普萘洛尔组比较无显著差异 (P >0 .0 5 )。结论 :曲美他嗪可拮抗异丙肾上腺素引起的大鼠心肌损伤 ,其机制与改善心肌能量代谢、抑制脂质过氧化有关     

白花丹参水提物对小鼠耐低氧能力的影响

目的观察白花丹参水提物对小鼠耐低氧能力的影响。方法50只小鼠随机平分为5组，低、中和高剂量实验组分别单剂量灌胃给予白花丹参10，20和40 g·kg 1，阳性对照组灌胃给予普萘洛尔20 mg·kg 1，空白对照组灌胃给予等体积0.9%氯化钠溶液。小鼠灌胃后40 min开始进行小鼠耐低氧能力实验，观察小鼠低氧存活时间和耗氧量变化。结果低、中和高剂量实验组小鼠常压低氧存活时间明显延长，耗氧量降低。结论白花丹参水提物能明显增强小鼠的耐低氧能力。     

黄蜀葵总黄酮对全脑缺血损伤的保护作用

目的　研究黄蜀葵总黄酮 (TFA)对脑缺血及再灌注损伤的保护作用。方法　结扎双侧颈总动脉建立小鼠脑缺血模型 ,观察小鼠 6h存活率 ,测定缺血脑组织中丙二醛(MDA)含量 ;采用小鼠氮气缺氧模型 ,观察小鼠存活时间 ;采用结扎双侧颈总动脉合并血压下降法建立兔脑缺血再灌注模型 ,兔脑缺血 60min后再灌注 3 0min ,记录脑缺血和再灌注的脑电图 (EEG) ,测定缺血脑组织的丙二醛 (MDA)、乳酸脱氢酶 (LDH)。结果　TFA(3 0、60、12 0mg·kg-1)延长小鼠缺氧后的存活时间和提高脑缺血后小鼠的存活率及能抑制脑组织中MDA的增高。TFA(12、2 4、48mg·kg-1)抑制兔脑缺血再灌注损伤所致的EEG、MDA、LDH变化。结论　TFA对脑缺血及再灌注损伤有保护作用 ,其机制可能与抗自由基和脂质过氧化有关     

实验性衰老小鼠肺功能和超微结构的变化及肉苁蓉多糖的影响

目的　观察实验性衰老小鼠肺组织细胞超微结构的退行性改变和肉苁蓉多糖对其的影响。方法　使用臭氧(Ozone,O3 )连续吸入 4wk致肺衰老模型 ,应用肉苁蓉多糖5 0 ,10 0mg·kg-1·d-1灌服模型小鼠 6wk ,检测衰老小鼠的耐缺氧能力、肺和血清中超氧化物歧化酶 (SOD)活性、丙二醛 (MDA)含量 ,电镜下观察肺组织细胞器和超微结构的变化。结果　臭氧所致实验性衰老小鼠耐缺氧能力明显下降 ;肺和血清中SOD降低、MDA升高。与模型组比较 ,肉苁蓉多糖能明显延长衰老小鼠耐缺氧时间 (P <0 0 1) ,提高血清中SOD活力、降低MDA含量 (P <0 0 1) ,延缓衰老小鼠肺细胞线粒体、板层小体等超微结构的退变 (P <0 0 1)。结论　肉苁蓉多糖能明显延缓实验性衰老小鼠肺的生理性退化与细胞形态学退变。     

魔芋葡甘聚糖对四氧嘧啶糖尿病小鼠高血糖的防治作用

目的　观察魔芋葡甘聚糖 (KGM )对糖尿病小鼠血糖的影响。方法　建立小鼠四氧嘧啶糖尿病模型 ,分组给药 ,测定血糖值。结果　预先 1h和 4hKGM 10 0、2 0 0mg·kg-1ig给药组小鼠血糖降低 ,与对照组比较差异有显著性(P <0 0 1) ;KGM 10 0、2 0 0mg·kg-1ig给药能明显降低四氧嘧啶糖尿病小鼠血糖水平 ,与对照组比较差异有显著性 (P<0 0 1) ;KGM 10 0mgig每天 2次连续 3d ,能明显减少小鼠的饮水量 ,与对照组比较差异有显著性 (P <0 0 1)。结论　KGM对四氧嘧啶糖尿病小鼠高血糖具有防治作用。     

黄连解毒汤有效部位对动物脑缺血缺氧的保护作用

目的研究黄连解毒汤有效部位(HLJDTAF)对小鼠的抗缺氧作用及对多发脑梗死大鼠能量代谢的影响.方法通过小鼠常压耐缺氧、小鼠亚硝酸钠中毒和断头试验,观察黄连解毒汤有效部位连续灌胃给药4d对缺氧的保护作用,同时观察该药对血细胞的影响;采用大鼠多发性脑梗死模型观察HLJDTAF对模型大鼠脑组织乳酸(LA)、乳酸脱氢酶(LDH)、Na -K ATP酶和Ca2 -Mg2 ATP酶的影响.结果HLJDTAF865,433,216mg·kg-1可明显延长小鼠常压密闭状态下的存活时间(与对照组比较P＜0.05);216mg·kg-1可明显延长小鼠亚硝酸钠中毒缺氧存活时间(与对照组比较P＜0.05);HLJDTAF865,433,216mg·kg-1可明显延长正常小鼠断头张口喘气时间(与对照组比较P＜0.05;P＜0.01),433mg·kg-1可提高小鼠血液中血红蛋白含量,同时升高白细胞和淋巴细胞数量(与对照组比较P＜0.05);HLJDTAF610,305mg·kg-1组可显著降低多发性脑梗塞大鼠脑组织中LA含量,提高LDH活性,提高Na -K ATP酶活性,153mg·kg-1也可提高LDH与Na -K ATP酶活性(与模型组比较P＜0.05;P＜0.01).结论HLJDTAF可提高小鼠耐缺氧能力,同时改善多发脑梗死大鼠脑组织能量代谢障碍,这可能是其脑保护作用的机制.     

茵陈素的耐缺氧作用

目的　观察茵陈素对物理 ,化学因素所致缺氧动物的保护作用。方法　分别采用减压、常压、小鼠断头、化学药品致动物缺氧以及测定整体、离体组织的氧耗量等方法。结果　ip茵陈素 15～ 6 0mg·kg-1能显著提高减压、常压、化学药物所致组织缺氧死亡鼠的存活率或存活时间 ,增加断头鼠头的张口次数 .降低小鼠整体、离体鼠 (心肌 )耗氧量 ,为阐明茵陈素的抗辐射、解化疗毒的作用机制提供实验依据。结论　茵陈素有良好的耐缺氧作用。     

苁蓉益肾颗粒对小鼠实验性缺氧的保护作用

目的观察苁蓉益肾颗粒对小鼠实验性缺氧的保护作用.方法采用常压和低压缺氧条件下分别观察小鼠平均存活时间和心肌耗氧量.结果苁蓉益肾颗粒高低剂量组均可使常压和低压缺氧条件下小鼠平均存活时间延长;降低常压条件下心肌耗氧量.结论苁蓉益肾颗粒能明显降低小鼠氧耗,保护缺氧心肌.     

铁皮枫斗颗粒对放射损伤小鼠造血功能的影响

目的研究铁皮枫斗颗粒(DCWD)对放射损伤小鼠造血功能的影响。方法BALB/c小鼠125只,随机分为正常对照组、单纯照射组及DCWD大、中、小剂量组。采用直线加速器6 mV X射线8.0 Gy或5.0Gy全身单次均匀照射,照前连续灌胃10 d,每天1次,照后继续给药至小鼠死亡或活杀。观察受8.0 Gy照射小鼠的存活情况,检测受5.0 Gy照射小鼠外周血白细胞计数(PWBC)、骨髓有核细胞数(BMC)及脾指数。结果8.0 Gy照射后,受照各组小鼠平均存活时间均在10 d之内,较正常对照组明显缩短(P<0.01),给药组较单纯照射组延长3~4 d(P<0.01);5.0 Gy照射后小鼠PWBC、BMC和脾指数均显著下降,给药组高于单纯照射组(P<0.05),且恢复快,但给药各组之间差异无统计学意义。结论DCWD能明显延长受照小鼠平均存活时间,提高其存活率,显著提高其PWBC、BMC和脾指数;DCWD对放射损伤具有一定的保护作用,其机制可能与促进骨髓造血功能恢复有关。     

Regulative effect of aqueous extract of Eichhornia crassipes on the oxygen uptake capacity and motion responses of mice under wet/cool stress

OBJECTIVE To investigate the regulative effect of aqueous extract of Eichhornia crassipes on the oxygen uptake capacity and motion responses of mice under wet/cool stress. METHODS KM mice were randomly divided into normal control group,model control group,Eichhornia crassipes lowdose group(0.5g·kg-1)and high dose group(1.5g·kg-1),then performed intragastric administration for a period of 7d.Wet/cold stressed mice model was established using repeated intermittent(3h·d-1,consecutive 7d)exposure method by placing mice into the exposure box which was covered by ice at the bottom(T<0℃;RH>85%).Oxygen consumption was observed during exposure.Inclined plane method(muscle coordination capacity test)was performed immediately after exposure.60-second video of exhaustive swimming(to calculate swimming speed)was taken 1hafter the last exposure,the exhaustive swimming time was recorded.RESULTS(1)Compared with normal control group,model control group showed significant improvement in oxygen consumption(P<0.01),with an increase up to 77.33%,while inclined plate time,swimming speed and exhaustive swimming time showed significant reduction(P<0.01),at the rates 46.3%,8.54% and 19.68%respectively.(2)Compared with normal control group,Eichhornia crassipes low dose group and high dose group both improved oxygen consumption significantly(P<0.01),at rates of 10.93% and 90.38%respectively.This indicated high-dose aqueous extract of Eichhornia crassipes could fulfil actual oxygen demand of wet/cold stressed mice effectively.Inclined plate and exhaustive swimming experiments indicated that low-dose aqueous extract of Eichhornia crassipes boosted physical power significantly,as its exhaustive swimming time was increased up to 56.61%.Meanwhile,high-dose aqueous extract of Eichhornia crassipes has significant regulative effect on muscle coordination capability and motion speed,which were increased by 17.38% and 11.17%,respectively.CONCLUSION Aqueous extract of Eichhornia crassipes has definite regulative effect on the oxygen uptake capacity and motion responses of wet/cold stressed mice.Aqueous extract of Eichhornia crassipes can achieve stress protective effect by improving oxygen uptake capacity,muscle coordination capacity and motion abilities.     

白芍总苷对小鼠整体氧耗动态观察

目的 观察白芍总苷对小鼠心肌耗氧量的影响。方法 采用整体氧耗动态观察中分离心肌氧耗方法。结果 给予白芍苷20mg/kg，小鼠整体耗氧量和心肌耗氧量的变化明显低于生理盐水组和异丙肾上腺素组（P＜0.01)。白芍总苷作用强度稍弱于阿替洛尔。结论 白芍总苷能明显降低心肌耗氧量。     

普萘洛尔致犬急性心衰模型的方法学研究

目的探讨普萘洛尔对比格犬诱导急性心力衰竭模型的可行性。方法静脉推注普萘洛尔诱导急性心力衰竭,静脉滴注普萘洛尔维持心衰,股动脉插管监测血流动力学指标变化,电磁流量计测量心输出量。结果与造模前基础值相比,普萘洛尔造模后心率、动脉收缩压、动脉舒张压、平均动脉压、左室内压下降速度和左室收缩压均下降(P<0.05~0.01),左室舒张末期压上升(P<0.01),左室内压上升速度和心输出量分别下降51.7%、41.1%(P<0.01),达到心衰标准,且上述指标在2 h内保持稳定。结论普萘洛尔建立急性心力衰竭模型稳定可行。     

The cardiodynamic and metabolic effects of carbochromen and propranolol on the isolated dog heart

Summary In the isolated canine heart-lung preparation modified to measure coronary outflow and myocardial oxygen consumption, an infusion of carbochromen of 1 mg/min produced an increase in coronary outflow of 120.0% and a decrease in myocardial oxygen consumption of 11.0% at a cumulative dose of 28.0±3.8 mg, resulting in an increase in efficiency of 22.4%. At a total dose of 40 mg, the corresponding figures were +181.0%, –15.0% and +38.0% respectively. No change in heart rate was observed. An infusion of propranolol of 1 mg/min, on the other hand, was characterized by decreases in myocardial contractility and heart rate starting with cumulative doses of 20 mg and 40 mg respectively. At a cumulative dose of 62.9±3.0 mg a marked degree of myocardial failure occurred (peak failure) characterized by a decrease in cardiac output (–53.3%), dp/dt (–50.8%), heart rate (–18.5%) and myocardial oxygen consumption (–25.5%). In a separate series exposed to the same infusion of propranolol but in which the decrease in heart rate was prevented by pacing, identical changes were observed except that myocardial oxygen consumption decreased only by 7.7%. It may be concluded from this study that carbochromen, in confirmation of reports by other investigators, increases coronary out-flow markedly. Carbochromen decreases myocardial oxygen consumption by a direct effect on myocardial metabolism as is evident from the fact that this decrease is not accompanied by changes in any of the parameters which are known to influence myocardial oxygen consumption such as heart rate. Propranolol has no effect on myocardial oxygen consumption unless it is given in a dose which produces myocardial failure and a decrease in heart rate. The decrease in heart rate following propranolol bears a close relationship to the decrease in myocardial oxygen consumption.     

蟾毒灵对裸鼠人胰腺癌的作用和诱导细胞调亡的研究

目的观察蟾毒灵对裸鼠人胰腺癌的疗效和诱导细胞凋亡作用。方法建立裸鼠人胰腺癌移植瘤模型,随机分为蟾毒灵低剂量组(1.0mg/kg)、蟾毒灵高剂量组(1.5mg/kg)、5-Fu组(24mg/kg)、5-Fu+低剂量蟾毒灵组(24mg/kg+1.0mg/kg),生理盐水(NS)组。腹腔注射给药,1次/d,连续给药6d。各组保留6只荷瘤鼠观察带瘤生存期,其余6只于用药第7天处死,测量鼠重变化、肿瘤生长抑制率;TUNEL法检测瘤体凋亡指数。结果治疗后,与NS相比,蟾毒灵高、低剂量组裸鼠体重无显著差异(P>0.05),5-Fu组、5-Fu+低剂量蟾毒灵组裸鼠体重明显降低差异(P<0.01);各用药组瘤体体积与NS组相比均显著缩小(P<0.05),蟾毒灵高剂量组较低剂量组瘤体体积显著缩小(P<0.05),蟾毒灵+5-Fu组较单纯蟾毒灵组瘤体体积显著缩小(P<0.05);蟾毒灵高、低剂量组平均生存期较NS组显著延长(P<0.05);蟾毒灵高剂量组凋亡指数明显高于其他各组(P<0.01)。结论蟾毒灵对裸鼠人胰腺癌移植瘤有显著的抑制作用,诱导肿瘤细胞凋亡可能是蟾毒灵的抗肿瘤机理之一。     

干姜水煎液对心肌细胞线粒体功能损伤的改善作用研究

目的:探讨干姜水煎液对阿霉素致H9c2心肌细胞线粒体功能损伤的改善作用。方法:以大鼠H9c2心肌细胞为研究对象,采用CCK-8法检测不同浓度干姜水煎液(0.125、0.25、0.5、1、2、4、8 mg/mL,以生药量计,下同)对其存活率的影响;采用高内涵活细胞成像系统检测低、中、高浓度干姜水煎液(0.125、0.25、0.5 mg/mL)对阿霉素(5μmol/L)致H9c2心肌细胞线粒体功能损伤后细胞形态学的影响,并对其相对细胞总数、相对活细胞荧光强度、相对死细胞荧光强度进行定量分析;采用生物能量分析仪检测干姜水煎液(0.5 mg/mL)对H9c2心肌细胞线粒体功能损伤后线粒体呼吸功能相关指标(耗氧率、细胞外酸化率、基线耗氧率、基线细胞外酸化率、应激耗氧率和应激细胞外酸化率)和能量代谢相关指标(基础呼吸水平、最大呼吸水平、ATP产生水平、H+质子渗漏水平、备用呼吸能力和非线粒体呼吸水平)的影响。结果:经0.125、0.25、0.5 mg/mL的干姜水煎液作用后,H9c2心肌细胞存活率显著升高(P<0.01)或差异无统计学意义(P>0.05)。阿霉素致H9c2心肌细胞线粒体功能损伤后,经0.125、0.25、0.5 mg/mL(或0.5 mg/mL)的干姜水煎液干预,细胞形态恢复正常,呈规则纤维状贴壁分布;相对细胞总数、活细胞荧光强度、耗氧率、细胞外酸化率、基线耗氧率、基线细胞外酸化率、应激耗氧率、应激细胞外酸化率、基础呼吸水平、最大呼吸水平、ATP产生水平、备用呼吸能力和非线粒体呼吸水平均显著升高(P<0.05或P<0.01),相对死细胞荧光强度、H+质子渗漏水平均显著降低(P<0.01)。结论:干姜水煎液可通过提高H9c2心肌细胞线线粒体呼吸功能和能量代谢,进而改善其粒体功能损伤。     

益气健身方抗疲劳和耐缺氧作用实验研究

目的研究益气健身方对小鼠的耐缺氧和抗疲劳作用。方法采用灌胃法给予小鼠不同剂量的益气健身方,分别测定小鼠的转棒时间、负重游泳时间及常压耐缺氧时间。结果益气健身方高、中、低剂量组(0.5、1.0、2.0g/kg)小鼠转棒时间较对照组显著延长(P<0.01),高、中剂量组负重游泳时间较对照组显著延长(P<0.05,P<0.01),高剂量组常压耐缺氧生存时间较对照组显著延长(P<0.05)。结论益气健身方具有一定的耐缺氧和抗疲劳作用。     

Pharmacokinetics and metabolism of oral doses of a 4′-methylthio derivative of propranolol in man

1. The objective of this study was to determine the oral dose pharmacokinetics and metabolism of 4′-methylthiopropranolol (MTP) in man and compare the results with observations for propranolol in previous studies.

2. Three women and five men received single oral doses of MTP, dose range 5-320 mg. Plasma concentration of MTP over time were measured by gas chromatography-mass spectrometry. MTP metabolites in urine were identified by comparative high-performance liquid chromatographic (HPLC) retention times and mass spectrometry with previously characterized reference compounds and quantified by HPLC.

3. The oral clearance of MTP of 1.2–1.41/min for the 80, 160 and 320 mg doses was about one third of the value previously reported for propranolol. The half-life for MTP (3.3–4.1 h) was, however, similar to that of propranolol. In contrast to propranolol, the peak (2.5 h) plasma concentrations of MTP increased linearly with dose (5-320 mg).

4. The oral clearance for MTP was about 2-fold higher in the men than in the women (P<0.01). In addition, the clearance of the (S)-enantiomer was about 30% higher than that of the (R)-enantiomer (P<0.05), which was a reversal of that seen with propranolol.

5. The metabolism of MTP resulted mainly in sulphur oxidation to sulphoxide and sulphone metabolites. These two metabolites accounted for 75% of the MTP dose. This switching from aromatic carbon oxidation for propranolol to sulphur oxidation for MTP is proposed as the basis of the lower oral clearance of MTP.

6. This study also demonstrated higher plasma binding of MTP (unbound fraction 3.7%) than of propranolol (10.5%; P<0.01), a factor probably contributing to decreased tissue distribution of MTP.