间断性屈膝缺血预适应对小鼠缺氧耐力的影响

目的：观察和比较两种后肢缺血法产生的缺血预适应对小鼠耐受缺氧能力的影响。方法：昆明小鼠96只,分成对照组、间断屈膝固定组（KF）或束缚大腿组（TT）进行缺血预适应。每天预适应1次,7 d后各组小鼠再分为3组分别进行常压耐缺氧实验、亚硝酸钠中毒实验和断头后心、脑耐缺血实验。结果：两种后肢缺血法小鼠常压耐缺氧时间均显著延长（P<0.01）,断头后张口呼吸时间显著高于对照组（P<0.05）。但对亚硝酸钠中毒生存时间和心脏跳动时间没有明显影响。结论：肢体缺血预适应能显著增强小鼠缺氧耐力。     

红托竹荪多糖抗疲劳和耐缺氧作用研究

考察红托竹荪多糖(Dictyophora rubrovalvata polysaccharide,DRP)抗疲劳和耐缺氧活性。采用水提醇沉法提取DRP,建立小鼠负重游泳模型和耐缺氧模型,同时灌胃不同剂量的DRP溶液,15 d后测定小鼠力竭游泳时间、耐缺氧时间以及小鼠力竭游泳后血乳酸(BLA)、血尿素氮(BUN)、超氧化物歧化酶(SOD)、丙二醛(MDA)和肝糖原、肌糖原含量。实验结果表明DRP能延长负重小鼠的游泳时间,降低疲劳小鼠BLA、BUN、MDA含量,升高SOD、肝糖原和肌糖原含量,延长小鼠常压耐缺氧存活时间。     

酸柏栀油软胶囊对小鼠耐缺氧和抗疲劳的实验研究

目的:研究酸柏栀油软胶囊耐缺氧和抗疲劳作用。方法:采用常压耐缺氧实验、亚硝酸钠中毒存活实验和急性脑缺血性缺氧实验,观察软胶囊对小鼠的耐缺氧作用;采用负重游泳法记录负重游泳时存活时间,观察药物对小鼠抗疲劳作用。结果:在耐缺氧方面,酸柏栀油软胶囊可以延长小鼠在常压条件下和亚硝酸钠中毒后的存活时间(P<0.05);在抗疲劳方面,酸柏栀油软胶囊能延长小鼠在负重情况下的存活时间,增加肝糖元含量,减少乳酸水平(P<0.05)。结论:酸柏栀油软胶囊能增强小鼠耐缺氧和抗疲劳能力。     

阿里红多糖对小鼠抗疲劳和耐缺氧的作用*

目的:研究阿里红多糖对小鼠的抗疲劳和耐缺氧作用。方法:将48只小鼠随机分为4组(n=12),即对照组,低、中、高剂量阿里红多糖组(100、200、400 mg/kg)。各组小鼠按0.20 ml/10 g每日连续灌胃21 d后,观察不同剂量的阿里红多糖对小鼠负重游泳时间,运动后血清尿素氮、血乳酸、肝糖原、肌糖原含量和常压耐缺氧存活时间、断头后呼吸维持时间的影响。结果:与对照组相比,阿里红多糖能延长小鼠负重游泳时间、耐缺氧存活时间及断头后呼吸维持时间,其中中、高剂量组差异均极显著(P＜0.01),低剂量组差异显著(P＜0.05);阿里红多糖能降低运动小鼠血清尿素氮、血乳酸含量,增加运动小鼠肝糖原、肌糖原含量,且大都差异显著(P＜0.05)或极显著(P＜ 0.01)。结论:阿里红多糖具有抗疲劳作用和提高耐缺氧能力作用。     

鸭胚多肽对小鼠抗疲劳、耐缺氧能力的影响

实验研究鸭胚多肽对小鼠机体抗疲劳、耐缺氧能力的影响。实验设对照组和实验组(鸭胚多肽低剂量、中剂量和高剂量组),连续灌胃小鼠30 d后,测定小鼠负重游泳力竭至死时间,并测定小鼠游泳后血清中乳酸(LD)含量、尿素氮(BUN)含量、葡萄糖(LG)含量、乳酸脱氢酶(LDH)活性,小鼠常压耐缺氧存活时间、亚硝酸钠中毒存活时间、急性脑缺血性存活时间。结果表明:鸭胚多肽能显著增加小鼠负重游泳时间、血清中LDH活性、小鼠亚硝酸钠中毒存活时间及急性脑缺血性存活时间,并能显著降低LD、BUN含量。说明鸭胚多肽能有效提高小鼠的抗疲劳、耐缺氧能力。     

罗汉果油的药理作用研究北大核心CSCD

采用小鼠灌胃给药研究罗汉果油的药理作用。给正常小鼠灌胃给药7d后,采用小鼠游泳方法及常压耐缺氧实验,观察罗汉果油对小鼠的抗疲劳和缺氧耐力作用。给正常小鼠灌胃给药10d后,测定血清中超氧化物岐化酶（SOD）活性及丙二醛（MDA）含量,观察罗汉果油的抗氧化作用。结果表明罗汉果油能明显延长小鼠游泳时间,并能延长常压耐缺氧时间及提高正常小鼠血清中SOD活性,降低MDA含量。罗汉果油具有明显的抗疲劳和耐缺氧,抗氧化等药理作用。     

白藜芦醇抗衰老作用的实验研究

目的：探讨白藜芦醇的抗衰老作用。方法：采用避暗实验观察白藜芦醇对小鼠学习记忆的影响,通过常压耐缺氧、断头耐缺氧、亚硝酸钠中毒造成的缺氧以及负重游泳实验,观察白藜芦醇对小鼠缺氧及耐力的影响;以AlCl3造成急性衰老小鼠模型,观察白藜芦醇对小鼠血中超氧化物歧化酶（SOD）活性的影响。结果：白藜芦醇各剂量组均能明显改善记忆障碍,与模型组比较差异有显著性（P〈0.01）。在耐力实验中,白藜芦醇可显著延长小鼠缺氧时间,与溶剂组比较有显著性差异（P〈0.05）。结论：白藜芦醇具有一定的抗衰老作用。     

贯叶连翘提取物对小鼠抗应激反应及运动力竭小鼠抗氧化活性的影响

目的：研究贯叶连翘提取物（HPLE）对小鼠抗应激反应及运动力竭小鼠抗氧化活性的影响。方法：ICR小鼠,雌雄各半,随机均分为生理盐水（NS）对照组及高、中、低剂量HPLE组。分别采用负重游泳、常压耐缺氧和耐低温实验,观察小鼠抗急性应激反应能力,HPLE组分别按1.5 g/kg、0.75 g/kg和0.38 g/kg,ig,Bid,连续给药7 d;NS组等体积生理盐水ig。另取ICR小鼠40只,雌雄各半。随机均分为NS对照组及HPLE高、中、低剂量组。分别按ig HPLE 1.5 g/kg、0.75 g/kg和0.38 g/kg,q.d;对照组：ig等量NS,qd。连续用药2周后,开始每天进行游泳训练0.5 h,到第21天后,游泳力竭后休息20 min,断头取血,制备血清,检测小鼠血清中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性和丙二醛（MDA）的含量变化。结果：HPLE可延长小鼠负重游泳时间,缺氧存活时间及提高耐低温能力,并能升高运动力竭小鼠血清中SOD和GSH-Px活性,降低MDA的含量。结论：HPLE可提高小鼠应激反应能力,并具有抗氧化活性。     

益寿汤对小鼠免疫和抗应激能力的影响

给小鼠益寿汤１ｇ／ｋｇ,２ｇ／ｋｇ,４ｇ／ｋｇ灌胃连续７ｄ,分别检测其抗应激能力和免疫功能的变化。结果表明：益寿汤４ｇ／ｋｇ组小鼠较对照组负重游泳耗竭时间和常压耐缺氧生存时间明显延长,益寿汤２ｇ／ｋｇ和４ｇ／ｋｇ可提高小鼠耐寒能力,各剂量益寿汤均可显著提高小鼠血清溶血素及碳粒廓清吞噬数,但对迟发型变态反应无明显影响。     

银杏内酯B和低氧预适应对小鼠急性缺氧损伤的保护作用

目的：通过观察缺氧预适应和银杏内酯B预处理对小鼠急性缺氧的影响,了解银杏内酯B的脑保护作用。方法：采用小鼠常压缺氧模型,观察小鼠的行为学并记录各组小鼠的最后死亡时间,脑组织含水量,用RT-PCR、Western blot分别检测各组小鼠皮层组织中RTP801mRNA表达和EPO蛋白表达。结果：银杏内酯B和低氧预适应均能明显延长常压缺氧小鼠的存活时间,降低脑水肿程度,并且银杏内酯组和低氧预适应组RTP801mRNA表达和EPO的表达均明显增加。结论：银杏内酯B与低氧预适应具有相类似的对抗小鼠急性低氧的作用,其脑保护作用与上调RTPS01mRNA和EPO蛋白的表达有关。     

Hypoxic preconditioning improves spatial cognitive ability in mice

Although it has been reported in a lot of studies that hypoxic preconditioning could protect the brain from hypoxic/ischemic injury, it is not clear whether hypoxic preconditioning could affect brain functions such as cognitive ability. This work aims at investigating the effect of hypoxic preconditioning on spatial cognitive ability in mice after acute and repeated hypoxic exposures. The mice were randomly divided into 3 groups: a control group in which mice were not exposed to hypoxia (H0) and experimental groups in which mice encountered hypoxia either once (H1) or 4 times (H4). Neural cell adhesion molecule (NCAM) expression, long-term potentiation (LTP) recording and Morris water maze test were used to measure the animals' cognitive ability. The tolerance time was progressively prolonged as exposure went on. The expression of both NCAM mRNA and NCAM protein as well as the LTP induction rate decreased in group H1, but recovered to control level in group H4. The performance of mice in the maze test was improved in H4 in comparison with that in both H1 and H0. These findings may indicate that spatial cognitive ability is improved in adult mice by their hypoxic preconditioning.     

通心络对低氧预适应小鼠神经元超微结构及内皮细胞自修复能力的影响

目的：观察低氧预适应对小鼠脑皮层神经元和内皮细胞超微结构的改变及通心络的作用。方法：40只小鼠随机分为正常对照组、低氧组、低氧预适应组和通心络组（低氧预适应＋通心络）,利用重复低氧5次复制低氧预适应小鼠模型后,记录小鼠每次低氧耐受的时间,观察脑皮层神经元和血管内皮细胞超微结构的改变。结果：随着低氧次数的增加,预适应组和通心络组小鼠耐受时间增加（P〈0．05或P〈0．01）。与预适应组比较,通心络组小鼠耐受时间增加（P〈0．05或P〈0．01）;低氧组小鼠脑皮层内皮细胞和神经元超微结构发生明显改变,预适应组小鼠脑组织神经元及血管内皮细胞超微结构改善,通心络组脑组织神经元及血管内皮细胞超微结构明显改善。结论：低氧预适应显示出机体具有强大的自修复能力,通心络能明显增强机体的自修复能力,提高自适应。     

低氧预适应对小鼠海马组织HIF-1与EPO低氧应答元件结合活性的影响

目的：观察低氧预适应对小鼠海马组织HIF-1与EPO的低氧应答元件（HRE）结合活性的变化,探讨这种变化与低氧预适应形成的关系。方法：小鼠低氧0次（H0）,1次（H1）,4次（H4）后取海马组织,应用凝胶迁移改变试验（EMSA）,染色体免疫共沉淀（ChIP）试验和荧光定量PCR（real—time PCR）技术,检测小鼠海马组织内HIF-1与EPO的低氧应答元件结合能力的变化。结果：EMSA体外结合实验及ChIP体内结合实验发现。H0、H1和H4组结合活力依次增强。结论：HIF-1与EPO的低氧应答元件结合增强可能参与预适应的形成。     

不同中药复方及不同提取方法提取液对小鼠耐缺氧作用的影响*

目的: 探讨不同中药处方组成及其不同提取方法的复方提取物对小鼠耐缺氧能力的影响,以优选其处方组成和制备提取方法。方法: 将雄性BALB/c小鼠随机分成6组:空白对照组、复方丹参组、复方红景天醇-水提取组(红景天、黄芪、黄精、枸杞子)、复方红景天水提取组、复方黄芪醇-水提取组(黄芪、黄精、枸杞子)、复方黄芪水提取组,每组30只,每组小鼠连续灌胃给药10 d,空白组灌胃灭菌注射用水,复方丹参组0.15 g/kg,复方红景天醇-水提取组和水提取组3 g/kg,复方黄芪醇-水提取组和水提取组1.7 g/kg。各组于末次灌胃1 h后进行常压耐缺氧实验、亚硝酸钠中毒存活实验和急性脑缺血缺氧实验,并测定小鼠脑组织氧化应激相关抗氧化物酶活性和代谢物含量。结果: 与空白对照组相比,复方丹参组、复方黄芪醇-水提取组和水提取组常压耐缺氧存活时间均显著延长(P＜0.01),脑缺血缺氧后张口喘气次数均显著增加(P＜0.05)。各组注射亚硝酸钠后存活时间没有统计学差异。与空白对照组相比,复方黄芪水提取组T-AOC、SOD、GSH和CAT活性均显著升高(P＜0.05,P＜0.01),MDA含量均显著降低(P＜0.01),与复方丹参组相比,复方黄芪水提取组SOD、CAT、GSH活性均显著升高(P＜0.01,P＜0.05),MDA含量显著降低(P＜0.05)。结论: 复方黄芪水提取组的耐缺氧效果最好,原复方红景天全方可以剔除红景天由黄芪、黄精、枸杞子组成,其提取方法为水提。     

The relationship between ischemic preconditioning-induced infarction size limitation and duration of test myocardial ischemia

Traditionally infarction size reduction by ischemic preconditioning is estimated in duration of test ischemia. This approach limits the understanding of real antiischemic efficacy of ischemic preconditioning. Present study was performed in the in vivo rat model of regional myocardial ischemia-reperfusion and showed that protective effect afforded by ischemic preconditioning progressively decreased with prolongation of test ischemia. There were no statistically significant differences in infarction size between control and preconditioned animals when the duration of test ischemia was increased up to 1 hour. Preconditioning ensured maximal infarction-limiting effect in duration of test ischemia varying from 20 to 40 minutes.     

间歇性低压低氧预处理对脑缺血大鼠海马p-p38 MAPK表达的影响

目的:本文旨在观察间歇性低压低氧(IH)预处理诱导脑缺血耐受过程中,大鼠海马CA1区磷酸化p38MAPK(p-p38 MAPK)的表达以及表达p-p38 MAPK的星形胶质细胞数量。方法:将30只健康雄性Wistar大鼠随机分为6组(n=5):假手术(sham)0 min组、IH+sham 0 min组、sham 7 d组、IH+sham 7 d组、损伤性缺血(Is)7 d组、IH+Is 7 d组。通过硫堇染色对各组大鼠海马CA1区锥体神经元进行神经病理学评价;免疫组织化学染色观察pp38 MAPK的表达;免疫荧光双标法观察表达p-p38 MAPK的星形胶质细胞数量。结果:IH预处理可以诱导脑缺血耐受,同时引起大鼠海马CA1区p-p38 MAPK的表达明显增加,且上调星形胶质细胞中p-p38 MAPK的表达。结论:低压低氧预处理促大鼠海马CA1区锥体神经元和星形胶质细胞中p-p38MAPK上调可能是IH预处理保护脑的一个途经。     

Protective Effect of Grape Seed Proanthocyanidins against Liver Ischemic Reperfusion Injury: Particularly in Diet-Induced Obese Mice

Background: Hepatic ischemia and reperfusion injury (IRI) is a major complication in liver surgery, and hepatic steatosis is a primary factor aggravating cellular injury during IRI. Both pro-inflammatory cytokines and reactive oxygen species (ROS) are key mediators of hepatic IRI. Ischemic preconditioning (IpreC), remote ischemia preconditioning (RIPC) and ischemic postconditioning (IpostC) have offered protections on hepatic IRI, but all these methods have their own shortcomings. Grape seed proanthocyanidins (GSP) has a broad spectrum of pharmacological properties against oxidative stress. Thus, GSP has potential protective effects against hepatic IRI.Methods: C57BL/6 mice suffering 30mins hepatic ischemia process were sacrificed after 1h reperfusion to build murine warm hepatic IRI model. The mice were injected GSP intraperitoneally 10, 20, 40mg/kg/day for 3 weeks as pharmacological preconditioning. Obese mice fed with high-fat diet for 24 weeks before used. Three pathways related to IRI, including ROS elimination, pro-inflammatory cytokines release and hypoxia responses were examined.Results: Our data show that GSP could significantly reduce hepatic IRI by protecting hepatocyte function and increasing the activity of ROS scavengers, as well as decreasing cytokines levels. At the same time, GSP also enhance the hypoxia tolerance response. Combined GSP and postconditioning can provided synergistic protection. In the obese mice suffering hepatic IRI group, GSP was more effective than postconditioning on protecting liver against IRI, and the combined strategy was obviously superior to the solo treatment.Conclusion: GSP could protect liver against IRI: particularly in high-fat diet induced obese mice. GSP used as pharmacological preconditioning and combined with other protocols have huge potential to be used in clinical.     

Changes of superoxide dismutase, glutathione perioxidase and lipid peroxides in the brain of mice preconditioned by hypoxia.

We have developed an animal model of hypoxic preconditioning and assumed that oxygen radicals and their endogenous scavenging enzymes may play an important role in the preconditioning. To test this hypothesis, activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of lipid peroxides (LPO) were measured during the preconditioning. Compared with unpreconditioned control animals, in animals exposed to hypoxia only once, the activities of SOD and GSH-Px in whole brain were found to be significantly decreased while the LPO content in the hippocampus significantly increased. However, those in animals exposed to 4 runs of hypoxia tended to return to control levels and were lower than those in animals exposed to 1 and 2 runs of hypoxia. Our results indicate that the oxygen radicals and their specific scavenging enzymes seem to be involved in the development of tolerance to hypoxia.     

Preconditioning with Associated Blocking of Ca2+ Inflow Alleviates Hypoxia-Induced Damage to Pancreatic β-Cells

Objective

Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed to characterize such effects and to test for and pharmacological means to alleviate a negative impact of hypoxia.

Methods and Design

Rat and human pancreatic islets were subjected to 5.5 h of hypoxia after which functional and viability parameters were measured subsequent to the hypoxic period and/or following a 22 h re-oxygenation period. Preconditioning with diazoxide or other agents was usually done during a 22 h period prior to hypoxia.

Results

Insulin contents decreased by 23% after 5.5 h of hypoxia and by 61% after a re-oxygenation period. Preconditioning with diazoxide time-dependently alleviated these hypoxia effects in rat and human islets. Hypoxia reduced proinsulin biosynthesis (³H-leucine incorporation into proinsulin) by 35%. Preconditioning counteracted this decrease by 91%. Preconditioning reduced hypoxia-induced necrosis by 40%, attenuated lowering of proteins of mitochondrial complexes I–IV and enhanced stimulation of HIF-1-alpha and phosphorylated AMPK proteins. Preconditioning by diazoxide was abolished by co-exposure to tolbutamide or elevated potassium (i.e. conditions which increase Ca²⁺ inflow). Preconditioning with nifedipine, a calcium channel blocker, partly reproduced effects of diazoxide. Both diazoxide and nifedipine moderately reduced basal glucose oxidation whereas glucose-induced oxygen consumption (tested with diazoxide) was unaffected. Preconditioning with diaxoxide enhanced insulin contents in transplants of rat islets to non-diabetic rats and lowered hyperglycemia vs. non-preconditioned islets in streptozotocin-diabetic rats. Preconditioning of human islet transplants lowered hyperglycemia in streptozotocin-diabetic nude mice.

Conclusions

1) Prior blocking of Ca²⁺ inflow associates with lesser hypoxia-induced damage, 2) preconditioning affects basal mitochondrial metabolism and accelerates activation of hypoxia-reactive and potentially protective factors, 3) results indicate that preconditioning by K⁺-ATP-channel openers has therapeutic potential for islet transplantations.