牛磺酸对大鼠缺血心肌Bcl-2和Bax蛋白表达的影响

目的：探讨大鼠心肌缺血损伤与凋亡相关基因bcl-2和bax表达的关系及牛磺酸的影响。方法：结扎大鼠冠状动脉左前降支建立心肌缺血模型。检测心肌线粒体中超氧化物歧化酶（SOD）、Ca^2 -ATPase活性及MDA（丙二醛）含量，用免疫组化法检测Bcl-2和Bax蛋白在心肌中的表达量。结果：结扎冠脉左前降支可致心肌线粒体MDA含量升高，SOD和Ca^2 －ATPase活性下降；缺血心肌Bax蛋白表达呈显著升高；牛磺酸能明显减少缺血心肌线粒体MDA的生成，降低心肌Bax蛋白的表达，增加Bcl-2蛋白的表达。结论：结扎大鼠冠状动脉左前降支导致的心肌缺血损伤与Bcl-2和Bax蛋白的表达有关。     

Holter监测冠心病无痛性心肌缺血发作规律的研究

目的 探讨冠心病无痛性心肌缺血的发作规律。方法 对确诊的486例冠心病患者，进行24小时Holter监到，观察无痛性心肌缺血发作的次数、时间及其与活动状态的关系。结果 486例冠心病患者中发生无症状性心肌缺血者335例，共698次，累计时间为3526分钟。其中619次与活动有关。6：00—12：00为无痛性心肌缺血发作高峰期，在此期间共发作389次，累计时间为2100分钟。具有无痛性心肌缺血的冠心病患者的死亡率为13．02％，高于有症状的冠心病患者的4．72％。两组死亡率间差别有显著性意义(P＜0．05)。结论 无痛性心肌缺血的发作有一定的规律，掌握该规律对于指导临床治疗、降低心脏猝死及预防心肌缺血的发作有一定的作用。     

抑肽酶预处理防护大鼠肝脏缺血再灌注损伤的实验研究

目的 探讨抑肽酶预处理对肝脏缺血再灌注损伤的防护作用。方法 SD大鼠80只，随机分为抑肽酶预处理和生理盐水预处理两组，观察肝脏缺血再灌注损伤引起及抑肽酶预处理的影响。结果 拟肽酶预处理组大鼠缺血再灌注损伤引起的血清谷丙转氨酶（ALT），谷草转氨酶（AST）活性及肝组织丙二醛（MDA）含量变化均显著低于生理盐水预处理组（P＜0．01）；肝细胞形态学异常改变也明显较生理盐水预处理组轻。结论 抑肽酶预处理对大鼠肝脏缺血再灌注损伤有明显的防治作用。     

高温、亚低温对大鼠脑缺血再灌注损伤的作用及其机制研究

目的：研究轻度高温、亚低温对大鼠脑缺血再灌注损伤组织兴奋性氨基酸（EAA）与氧自由基的相互关系及病理损伤程度的影响。方法：60只Wistar大鼠按不同脑温条件随机分为生化组（n=28）和病理组（n=32)，采用改良Nagasawa局灶脑缺血再灌注模型，观察脑缺血再灌注损伤组织谷氨酸（Glu），超氧化物歧化酶（SOD）、丙二醛（MDA）的变化及光镜，电镜下的病理变化。结果：轻度高温明显加重常温脑缺血再灌注损伤组织Glu、MDA的升高（P＜0．01）及SOD的下降（P＜0．05），加重常温脑缺血再灌注组织病理损伤程度，亚低温的作用则相反，结论：轻度高温可能通过同时促进EAA合成，释放和氧自由基生成系统活化，造成大鼠脑缺血再灌注损组织损伤加重；亚低温可能通过同时抑制EAA合成，释放和氧自由基生成系统活化，减轻大鼠脑缺血再灌注组织损伤程度，对大鼠脑缺血再灌注损伤组织起保护作用。     

四君子汤对缺血再灌注损伤大鼠自由基代谢影响的实验研究

从抗氧化角度探讨了四君子汤抗氧化的作用机制。结果表明，显著提高缺彬再灌损伤大鼠脑、血清中SOD活力，降低MDA含量；在体外实验中，明显抑制脑过氧化脂质的生成，具有清除羟自由基、超氧阴离子的作用。结论是四君子汤具有一定的抗氧化作用，健脾化痰抗氧化理论有一定的实验依据。     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

L-arginine对局灶脑缺血脑细胞凋亡和微血管密度的影响

目的探讨NO合成底物左旋-精氨酸(L-Arg)对兔局灶脑缺血后血管再生和脑细胞凋亡的影响。方法兔局灶脑缺血后应用L-Arg,流式细胞仪定量分析细胞凋亡率的变化,CD34免疫组织化学测脑组织微血管密度(MVD),脑组织含水率评价脑水肿。结果与对照组比较,L-Arg组脑细胞凋亡率明显减少(8.72±2.62 vs 16.62±2.82,P<0.01),同时脑组织MVD却明显增加(1.21±0.43 vs 0.69±0.22,P<0.01)。结论外源性L-Arg可减少缺血后脑细胞凋亡并促进缺血后血管再生,对局灶脑缺血具有重要的神经保护作用。     

^1H-magnetic resonance spectroscopy screening for animals with acute cerebral infraction suitable forthrombolytic therapy

BACKGROUND: As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy (1H-MRS) may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke. OBJECTIVE: To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability. DESIGN: Randomly controlled animal study. SETTINGS: Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS: Eleven healthy adult Sprague-Dawley (SD) rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology [SCXK (e) 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS: The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group (n =6) and 60-minute self-thrombo-embolism group (n =5). Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid (NAA)/phosphocreatine (PCr) + creatine (Cr), choline phosphate (Cho)/PCr+Cr and lactic acid (Lac)/PCr+Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope. MAIN OUTCOME MEASURES: ① Metabolic changes of NAA/PCr+Cr, Cho/PCr+Cr and Lac/PCr+Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue. RESULTS: Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests : In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy (0.252±0.01, 0.603±0.01, P < 0.01). Lac/(PCr+Cr) ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis (P < 0.01). The NAA/ (PCr+Cr) ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis (0.922±0.16, 1.196±0.01, P < 0.05). In 60-minute self-thrombo-embolism group, the Lac/(PCr+Cr) ratio was higher at 3 hours after thrombolysis than that before thrombolysis (0.846±0.12, 0.601±0.11, P < 0.05) and the NAA/(PCr+Cr) decreased at 3 hours after the embolism. Fluctuation of NAA/ (PCr+Cr) ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image: T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA > 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations: Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateral part of corpus striatum. CONCLUSION: ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.     

缺氧诱导因子-lα与脑缺氧缺血性损伤

缺氧诱导因子-lα（hypoxia-inducible factor-1alpha，HIF-lα）是近来发现的广泛存在于哺乳动物和人体内的一种缺氧应答调控因子，在调节缺氧诱导的基因表达中起关键性作用。它可调节表达多种靶基因如血管内皮生长因子、促红细胞生成素等，对改善脑缺氧缺血后能量代谢障碍、促进脑血流动力学恢复、抑制兴奋性氨基酸毒性、减少细胞凋亡等起重要作用。通过进一步对HIF-lα及其靶基因的研究，可能为临床治疗脑缺氧缺血性损伤提供了一种新的治疗策略。     

用99Tcm-HL91评价鼠心肌缺血模型

目的 探讨乏氧心肌显像剂99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)用于诊断实验性缺血心肌的价值.方法 建立大鼠心肌在体缺血再灌注模型,采用体外放射自显影法检测正常对照组(6只)、缺血再灌注组(8只)及无再灌注组(8只)鼠心肌对99Tcm-HL91的摄取.结果 对照组和无再灌注组心肌未见局灶性放射性浓聚,再灌注组心肌非坏死区有较高放射性浓聚,与正常心肌组织的摄取比值为1.634±0.354.结论 99Tcm-HL91表现出较强的亲乏氧组织特性,能较好区分存活和梗死心肌.