慢性阻塞性肺疾病大鼠模型制备及参七虫草胶囊对肺组织超微结构的影响

目的：观察参七虫草胶囊对慢性阻塞性肺疾病（COPD）模型大鼠肺组织超微结构的影响。方法：清洁级Wistar大鼠50只被随机分为正常对照组、COPD模型组、参七虫草胶囊高剂量组、参七虫草胶囊低剂量组和金水宝胶囊组，每组10只。采用香烟雾熏加脂多糖（LPS）气管滴入方法复制大鼠COPD模型。利用光镜和透射电镜方法并结合图像分析技术观察各组大鼠肺组织病理形态学变化，气管壁及腺体层厚度，计算线粒体病变率。结果：COPD模型组大鼠肺组织形态出现明显异常改变。线粒体肿胀肥大、空泡变、嵴突病变的发生率明显增高。与COPD模型组相比，参七虫草胶囊高、低剂量组肺组织病理损伤明显减轻；气管壁及腺体层厚度均明显变薄（P〈0．01和P〈0．05）；线粒体肿胀肥大、空泡变、嵴突病变发生率均显著降低（P均〈0．05）。金水宝胶囊组肺组织病理损伤较模型组亦有所减轻，但作用不如参七虫草胶囊组显著；线粒体病变发生率与COPD模型组相当。结论：参七虫草胶囊可以延缓和改善COPD模型形成。     

血管壁和血管内皮细胞超微结构在急性机械性脑血管痉挛早期的变化

背景:某些颅脑手术中难免会对脑血管进行牵拉、夹闭等机械性刺激,导致急性机械性脑血管痉挛的发生,目前这种急性机械性脑血管痉挛的病理生理及病理预后尚不清楚。目的:观察猫大脑中动脉血管直径、脑血流量、血管壁和血管内皮细胞超微结构在机械性刺激痉挛后早期(2h)的变化。设计:开放性实验。单位:首都医科大学附属北京天坛医院神经内科和北京市神经外科研究所。材料:选用健康成年的杂种猫6只,雌雄不拘,体质量2.5～3.5kg,由中国医学科学实验动物研究所提供。Periflux5010型激光多普勒血流仪(瑞典Perimed公司)。方法:实验于2005-08/2006-03在北京市神经外科研究所完成。200g/L水合氯醛腹腔注射(2mL/kg)麻醉后,取俯卧位。正中切开头皮,于前囟后1.5cm,旁开1.5cm开方形骨窗,8×10mm,挑破硬脑膜,选择无血管或少血管的脑表面固定激光多普勒血流计的微细探头。再使动物侧卧位,利用手术显微镜,通过眶下入路,暴露右侧大脑中动脉。选择大脑中动脉跨越嗅束前部位,利用钝性器械重复刺激大脑中动脉,频率为100次/min,持续30min。分别于刺激前,刺激结束后0,0.5,1.0,1.5,2.0h测量刺激前后大脑中动脉直径的变化,监测皮层脑组织灌流指数的变化,观察刺激后2h大脑中动脉血管壁和内皮细胞超微结构的变化。主要观察指标:刺激前,刺激结束后0,0.5,1.0,1.5,2.0h大脑中动脉直径和皮层脑组织灌流指数的变化以及刺激2h后大脑中动脉血管壁和内皮细胞超微结构的变化。结果:纳入6只实验动物全部进入结果分析。①大脑中动脉直径的变化:刺激结束后0,0.5,1.0h大脑中动脉直径分别为(0.617±0.129),(0.723±0.082),(0.840±0.084)mm,与刺激前比较,明显变窄[(0.897±0.066)mm,t=4.74,4.017,1.299,P<0.01]。②脑组织灌流指数的变化:刺激结束后0,0.5,1.0,1.5,2.0h灌流指数分别为67.8±18.5,82.5±17.5,89.8±24.0,94.0±22.2,98.5±21.0,明显低于刺激前(159.2±23.5,t=4.716～7.469,P<0.01)。③大脑中动脉超微结构的变化:大脑中动脉经急性机械性刺激后早期(2h)内皮细胞染色质边集,凝聚成新月形小体,线粒体嵴模糊不清。结论:机械性刺激猫大脑中动脉可导致脑血管痉挛。刺激后早期(2h)即出现内皮细胞超微结构的变化,显示内皮细胞的凋亡现象。提示颅脑手术中对脑血管的机械性刺激应尽可能的轻微,尽量减少对脑血管的机械性刺激,避免急性脑血管痉挛的发生。     

自体肺组织修补胸内食管缺损

背景:食管切除术需要行食管替代修补,在常规腹腔脏器不能使用的情况下,临床上缺乏有效的食管替代修补物。目的:探寻自体带血运的肺组织瓣修补胸内食管不规则缺损的新方法,为临床应用提供动物实验依据。设计:观察性动物实验。单位:中国医科大学附属第二医院胸外科。材料:实验于2003-01/2004-06在中国医科大学附属第二医院动物实验室完成。选用健康成年杂种犬14只,体质量12￣18kg,雌雄不限,由中国医科大学附属第二医院动物实验室提供(许可证号:SYXK辽2003-0019)。方法:14只实验犬麻醉后行右肺中叶游离,结扎切断右肺中叶支气管,不损伤肺动静脉,制成肺组织瓣作为修补物。将实验犬的胸内食管行全层侧壁切除,缺损长4cm,环1/2￣2/3管腔。将肺组织瓣覆盖于食管缺损处,与食管断面相吻合。术后3d静脉输液维持营养,术后第7天经口进全流食,2周过渡为半流食。观察实验犬能否正常经口进食及其存活情况。术后2,4,6,8,10周各处死2只实验犬,观察食管修补处愈合情况,并行光镜、透射电镜、食管钡餐及内镜检查。主要观察指标:①术后实验犬的存活和进食情况。②实验犬食管修补处的愈合情况。结果:14只实验犬存活11只,其余3只犬于术后1周内死亡。①术后实验犬的存活和进食情况:实验犬11例存活,最长存活时间超过170周;存活犬均能正常经口进食。②实验犬食管修补处的愈合情况:术后2周,光镜下见替代物管腔表面有胶原及炎性渗出物,两端近吻合口处见少许上皮形成,为一两层鳞状上皮细胞,排列欠规则。术后4￣6周,光镜下见替代物管腔表面为复层鳞状上皮细胞,分3￣5层。术后8￣10周,肉眼观察食管缺损处完全被具有正常外观的食管黏膜所覆盖。光镜示食管替代物的管腔表面可见6￣8层复层鳞状上皮细胞覆盖。肺组织瓣的病理改变主要为肺泡萎陷,肺组织纤维化,可见散在的炎性细胞。透射电镜见食管缺损处肺组织瓣的表面有新生的分层的鳞状上皮细胞。术后8周食管钡餐检查发现钡剂顺利通过食管缺损处。术后10周食管内镜见食管缺损处管腔内完全覆盖着正常外观的食管黏膜。结论:应用自体肺组织瓣修补胸内食管不规则缺损可作为一种简便易行的新方法。     

螺旋藻多糖对衰老小鼠肺细胞凋亡与超微结构的影响

目的:研究螺旋藻多糖(polysaccharidefromspirulinaplatensis,PSP)对衰老模型肺细胞凋亡、超微结构的作用及作用机制。方法:实验选用2月龄健康ICR品系小鼠50只,雌雄各半。随机数字表法随机分为模型组和PSP高、中、低3个剂量组及对照组,每组10只。取2月龄小鼠在常规条件下饲养11个月,制成自然衰老模型,应用PSP20,40,80mg/kg剂量分别灌服衰老小鼠6周,借助荧光显微镜研究肺组织细胞凋亡、电子显微镜下的形态学变化。结果:衰老可诱导肺组织细胞凋亡及肺泡Ⅱ型上皮细胞超微结构的改变,PSP可明显抑制肺组织细胞凋亡,使凋亡细胞数减少,改善肺泡上皮细胞的结构与功能。PSP明显减轻衰老引起的肺细胞凋亡,PSP高剂量组对凋亡改变相应减轻,细胞凋亡率呈下降趋势且明显犤(14.2±2.24)%犦,与模型组犤(23.7±5.53)%犦比较,差异有非常显著性意义(t=4.6721,P<0.01);PSP中、低剂量组犤(16.3±3.79)%,(19.6±4.61)%犦与模型组比较,差异有显著性意义t=3.2054,P<0.01;(t=1.6219,P<0.05);PSP高中剂量与对照组犤(12.8±3.54)%犦比较,差异无显著性意义(P>0.05),PSP低剂量与对照组比较,差异有显著性意义(t=3.5193,P<0.01)。结论:螺旋藻多糖对衰老小鼠肺组织细胞的退行性变化具有改善或延缓作用。     

还元注射液对实验性脑出血大鼠脑组织显微、超微结构的影响

目的探讨还元注射液对实验性脑出血大鼠脑组织显微、超微结构的影响及保护作用. 方法将 30只 SD大鼠随机分为正常组、模型组和还元组,每组 10只.各组于造模后 2 h分别腹腔注射生理盐水和还元注射液 1 mL/(100g.次 ), 2次 /d,共给药 3 d.第 4天断头处死迅速取脑,制成光镜、电镜片,观察组织学变化. 结果①正常组光镜、电镜下脑组织结构正常;②模型组光镜下,血肿范围大,充满变性红细胞,脑组织变性、坏死,毛细血管严重水肿;电镜下,神经细胞和胶质细胞明显肿胀,胞浆内大部分细胞器消失,染色质消失,神经细胞脱髓鞘,轴浆消失;③还元组光镜下,血肿形成囊肿,与周围脑组织界限不十分明显,血肿内有大量的胶质细胞和巨噬细胞,血肿周围无明显变性神经细胞,毛细血管无明显水肿;电镜下,神经细胞和胶质细胞无明显肿胀,胞浆内细胞器结构基本完整,神经纤维结构大致正常. 结论还元注射液对实验性脑出血大鼠脑组织结构具有保护作用.     

针刺对大鼠受损腰神经根超微结构及炎性介质的影响

背景腰神经受压后造成神经功能损害和神经行为的异常,不但与受压迫物的机械性损伤有关,而且与压迫造成的炎症反应有关.目的建立腰神经根压迫症的动物模型,探讨针刺对模鼠受损腰神经根超微结构及炎性介质的影响.设计完全随机对照实验.单位上海交通大学附属第六人民医院针推伤科.材料实验于2001-01/2004-01在上海交通大学附属第六人民医院试验动物中心完成.将SD雄性大鼠90只随机分为造模组45只和造模+电针组45只.方法腹腔注射氯胺酮麻醉,以L5-6棘突间隙为中心,咬除L5-6棘突、右侧椎板和关节突,将特制的硅胶片置于右侧L5神经根出硬膜囊处,局部固定,逐层缝合,无菌纱布覆盖.造模组造模后常规饲养,不作任何处理.造模+电针组于造模后第1天取28号3.33 cm(1.0寸)毫针,针刺右后肢环跳、阳陵泉与受压神经根相应节段右侧的夹脊穴.造模(电针)后15 d和30 d,取压迫区受损腰神经根组织经处理后于电镜、光镜下观察,同时测定其地诺前列酮及5-羟色胺等炎症递质的含量.主要观察指标[1]各组大鼠受损腰神经根组织于电镜、光镜下观察结果.[2]各组大鼠受压神经根组织内地诺前列酮及5-羟色胺含量.结果90只大鼠均进入结果分析.[1]造模+电针15 d组较造模15 d组神经纤维周围充血、水肿及神经根纤维脱髓鞘变较轻,许旺氏细胞结构基本正常,造模30 d组神经纤维周围大量炎细胞聚集,神经根纤维严重脱髓鞘变,神经纤维间隙明显增宽,并见红细胞渗出.造模+电针30 d组脱髓鞘变较轻,并缓解神经内水肿.[2]造模+电针15 d和30 d组大鼠受压神经根局部组织内地诺前列酮明显低于造模15 d和30 d组[(61.17±9.77),(76.65±7.39)ng/L;(56.05±7.98),(71.04±6.99)ng/L,P＜0.01].造模+电针15 d和30 d组大鼠受压神经根局部组织内5-羟色胺含量明显低于造模15 d和30 d组[(1 413.4±194.5),(2 587.7±214.7)ng/L(780.4±133.0),(1 355.0±147.7)ng/L,P＜0.01].结论电针可缓解受损腰神经根周围炎性反应,改善腰神经根超微结构,并且具有降低压迫腰神经根组织内地诺前列酮及5-羟色胺含量,部分抑制炎症反应的作用.     

电针对实验性糖尿病周围神经病变大鼠坐骨神经传导速度和超微结构的影响

目的:观察电针对实验性糖尿病周围神经病变大鼠坐骨神经传导速度及神经纤维超微结构的影响。方法:实验于2005-01/12在上海中医药大学附属岳阳中西医结合医院中心实验室完成。选用清洁级雄性Wistar大鼠100只,按随机数字表法选取15只作为正常对照组。在链脲佐菌素制备实验性糖尿病大鼠(n=85)基础上制备实验性糖尿病周围神经病变大鼠模型,以空腹血糖≥15mmol/L,坐骨神经感觉神经传导速度,运动神经传导速度明显减慢、摆尾温度阈值升高及坐骨神经有髓纤维形态学改变为造模成功的标准。在确认实验性糖尿病周围神经病变大鼠模型成功的基础上,采用随机数字表法抽取60只大鼠,分为3组,即电针经(组、电针非经(组、模型对照组,每组20只。①电针经(组:取肾俞(双)、足三里(双)(,将大鼠固定,针刺0.5cm,并接电针治疗仪,连续波,频率2Hz,20min/次,隔日1次,共治疗12次。②电针非经(组:将大鼠尾尖作为刺激点,具体方法和治疗次数同上。③模型对照组:不作任何治疗,只作与电针经(组相同的固定。④正常对照组:作与电针经(组相同的固定。造模后4周,以神经电生理法测试各组大鼠的运动神经、感觉神经传导速度;造模后8周,应用透射电镜观察各组大鼠的坐骨神经组织超微结构。结果:实验过程中模型对照组、电针非经(组及电针经(组大鼠分别死亡5,4,1只,因此进入结果分析每组分别抽取15只进行指标检测。①各组大鼠造模4周时的坐骨神经传导速度比较:模型对照组的运动神经传导速度、感觉神经传导速度显著低于正常对照组(31.37±3.70,18.17±9.54;41.30±1.15,44.22±8.80)m/s(P<0.01)。电针经(组经治疗后运动神经传导速度、感觉神经传导速度显著高于模型对照组(38.04±2.01,37.98±5.10)m/s(P<0.01),但未达到正常对照组水平(P<0.05);电针非经(组大鼠的运动神经传导速度、感觉神经传导速度与模型对照组差异无显著性意义(32.74±5.42,21.39±5.61)m/s(P>0.05)。②各组大鼠造模8周时的坐骨神经超微结构比较:模型对照组大鼠坐骨神经有髓神经纤维髓鞘结构模糊、松散、排列紊乱,出现空泡状缺损。电针非经(组大鼠坐骨神经有髓神经纤维髓鞘结构松散、排列紊乱,出现断裂或空泡状缺损。电针经(组大鼠坐骨神经髓纤维髓鞘结构损伤脱失的程度较模型对照组有所减轻,但未达到正常对照组水平。结论:电针对糖尿病周围神经病变具有一定的防治作用,其作用可能是通过改善糖尿病周围神经病变大鼠周围神经有髓纤维的形态及功能而实现的。     

颅脑损伤24h内大鼠肺组织结构和功能的改变

目的：观察大鼠颅脑损伤24h内肺组织结构和功能的改变。 方法：实验于2004-09／2005-01在北京市神经外科研究所动物实验室完成。选择雄性SD大鼠52只，随机数字表法分为对照组10只和颅脑损伤组42只。颅脑损伤组采用60g重物从100cm高度自由坠落建立弥漫性闭合性颅脑损伤动物模型。于损伤后6h和24h各选取14只大鼠进行肺组织透射电镜观察、血气分析、肺灌洗液白蛋白浓度测定、肺湿／干比和脑湿／干比测定、肺组织和脑组织光镜病理检查，并与伤后1min内死亡大鼠的各项指标进行比较。 结果：纳入动物52只，均进入结果分析，伤后1min内死亡大鼠14只，死亡率为33.3％。①伤后1min内死亡大鼠肺灌洗液白蛋白浓度、肺湿／干比明显高于对照组、颅脑损伤组损伤后6，24h大鼠[分别为（1.33&;#177;1．02），（0．10&;#177;0．07），（0．24&;#177;0．16），（0．18&;#177;0．12）g/L；5．64&;#177;0．74，4．44&;#177;0．09，4．59&;#177;0．16，4．91&;#177;0．191，肺病理评分明显升高。②颅脑损伤组pH、标准碳酸氢根、脑湿／干比与对照组比较无明显差异。 结论：6000g&;#183;cm的冲击力可以成功地复制出神经源性肺水肿动物模型。在颅脑损伤后24h之内，血气分析、肺湿／干比及肺部病理变化逐渐加重。     

脑卒中后抑郁状态动物模型的建立

目的：建立脑卒中后抑郁状态（PSD）动物模型。方法：采用Wistar大鼠双侧颈总动脉结扎,联合孤养和慢性温和性应激刺激,造成PSD动物模型。结果：模型组大鼠蔗糖水饮用量、旷野试验中水平及垂直得分均小于正常组,差异有统计学意义（P〈0.01）。结论：PSD动物模型能充分模拟PSD患者的核心症状,实验重复性较好,是研究PSD的理想模型。     

犬自体肺组织瓣修补食管壁部分缺损的可行性

目的:分析犬自体肺组织瓣修补食管壁部分缺损的可行性。方法:实验于2003-01/2004-11在中国医科大学附属第二医院动物实验室完成。选用健康成年杂种犬20只,按随机数字表法分为2组,即支架组和无支架组,每组10只。20只实验犬经右胸第5肋间进胸,于胸内中段食管处胸内食管侧壁制成长4cm,环1/2~2/3周径全层缺损。于相应部位选择适当的肺组织,制成带蒂类舌状肺组织瓣。两组均将肺组织瓣覆盖并缝合固定于食管缺损处,支架组于食管缺损内衬自扩性记忆合金支架(管腔直径2.0cm、长6.0cm)并固定。术后抗炎及营养支持治疗。观察实验犬术后情况,并于术后2,4,6,8,10和12周定期处死实验犬行组织学观察。结果:无支架组实验犬存活7只,其中1只犬存活>24个月;支架组存活6只。①实验犬术后一般情况:存活犬于术后均能正常经口进食,早期有进食后呕吐,再吃下呕吐食物的现象,以支架组明显。②组织学观察结果:术后2周,无支架组均可见替代物表面有胶原及炎性渗出物,边缘见1~2层鳞状上皮细胞;支架组除有无支架组基本表现外,可见支架固定良好,光镜下见网架压迫处有较多中性粒细胞浸润。4~6周,两组均可见替代物表面有新生的3~5层复层鳞状上皮细胞;支架组见支架已基本陷入黏膜层内。8~10周,两组均可见管腔表面有6~8层新生复层鳞状上皮细胞;支架组网架边缘瘢痕组织增生,支架完全被包裹,炎症较重的局部有细胞爬行中断现象或新生细胞层数较薄,多为一两层。结论:应用自体肺组织瓣修补食管壁部分缺损是可行的,但支架组支架对食管修补处组织刺激大,炎性反应重,瘢痕重,因此如何选择合适的支撑物是今后替代节段性食管缺损面临的重要问题。     

Effects of adenosine on extravascular lung water content in endotoxemic pigs.

OBJECTIVE: To investigate whether adenosine protects against endotoxin-induced increments in extravascular lung water content. DESIGN: Prospective, randomized, animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one anesthetized juvenile pigs. INTERVENTIONS: The animals were divided into two groups subjected to endotoxin infusion: Endotoxin alone (n = 7), or endotoxin combined with adenosine infusion (n = 7) administered during the whole experimental period. Two other groups were exposed to anesthesia alone (n = 4) or adenosine infusion alone (n = 3), respectively. MEASUREMENTS AND MAIN RESULTS: Central hemodynamic variables and extravascular lung water, as assessed by the thermal dye dilution double indicator technique, were monitored. Plasma endothelin-1 concentrations were measured hourly. Extravascular lung water increased significantly in response to endotoxemia (p <.001) along with an increase in pulmonary microvascular pressure (P(mv) [p <.01]). Although the Pmv increased less in endotoxemic animals exposed to adenosine infusion, no intergroup difference was found. From 4 through 6 hrs, adenosine-treated pigs displayed only half of the extravascular lung water content of nontreated animals (p <.01). The latter did not differ from that of anesthetized controls receiving anesthesia or adenosine alone. Adenosine administered alone had no effect on P(mv). In pigs receiving adenosine alone, extravascular lung water content reached nadir after 3 hrs. In both endotoxin groups, plasma endothelin-1 concentration increased two-fold, peaking 4-6 hrs after the start of endotoxin infusion (p <.001). CONCLUSIONS: The endotoxin-induced increase in lung extravascular water was hampered by intravenously infused adenosine in the presence of a nonsignificantly reduced microvascular pressure. This leaves reduced microvascular permeability the most likely reason for the beneficial effect of adenosine.     

脑出血大鼠局部脑血流量和脑水分含量变化的研究

目的：探讨脑出血大鼠局部脑血流量（ｒＣＢＦ）变化规律及脑出血后继发性脑缺血与脑水肿的关系。方法：采用新鲜未肝素化自体动脉血注入大鼠尾状核建立脑出血模型，以氢清除法测定ｒＣＢＦ，以干湿重法测定脑水分含量，观察脑出血后２４小时内两侧尾状核、丘脑和额叶皮质ｒＣＢＦ和脑各部位水分含量的变化。结果：脑出血后血肿周围脑组织ｒＣＢＦ迅速下降，出血４小时起脑水分含量明显增加，血肿远隔区同样受到影响。脑水肿区域与ｒＣＢＦ下降范围基本一致，但脑出血后２４小时内脑水肿高峰期迟发于ｒＣＢＦ下降高峰期。结论：实验大鼠脑出血后存在广泛脑缺血和严重脑水肿；ｒＣＢＦ下降是脑水肿发生、发展的重要原因     

黄芪注射液对实验性脑出血脑含水量和细胞超微结构的影响

目的:研究黄芪注射液对大鼠实验性脑出血后脑含水量和细胞超微结构的影响。方法:采用肝素化Ⅶ型胶原酶脑内注入法制作大鼠脑出血模型。将60只SD大鼠(雌雄不限,体重300～350g)随机分成2个治疗组(手术同时治疗组、术后6h治疗组A共40只)和出血对照组(共20只)。治疗组每日经腹腔给予黄芪注射液1次。各组分别于第4、7天处死,用于脑组织含水量测定。另取30只SD大鼠分为正常组、出血组、术后6h治疗组B,于术后第4天处死取材,制作电镜标本,用透射式电子显微镜观察细胞超微结构变化。结果:(1)脑出血后1～3d各组大鼠脑水肿明显,在出血后7d脑水肿明显减轻。(2)各治疗组脑含水量较出血对照组明显降低,差异有显著性(P<0.01)。第4天,术后6h治疗组A脑含水量明显少于出血对照组(P<0.01)。(3)术后6h治疗组B血肿周围区细胞超微结构破坏较出血组轻。结论:(1)黄芪注射液能降低大鼠脑出血后脑组织含水量。(2)黄芪注射液对血肿周围区细胞超微结构有保护作用。     

Assessment of lung water content by roentgen videodensitometry

In 17 anesthetized and mechanically ventilated pigs, different degrees of lung injury were induced by iv infusion of oleic acid (mean dose 0.1 ml/kg). The change in radiologic density of the chest was measured by a videodensitometer before and 4 h after oleic acid infusion. The lungs were then removed for determination of the wet/dry weight ratio (WW/DW). The change in radiologic density was significantly correlated to WW/DW (r = .87) and to the changes in end-inspiratory pressure (r = .80), mean pulmonary arterial pressure (r = .77) and venous admixture (r = .79), but not to changes in the oncotic-hydrostatic pressure gradient of the lungs (r = .46). Roentgen videodensitometry appears to be a useful method for assessing changes in extravascular lung water content.     

打击伤对大鼠延髓超微结构及钙积聚的影响

目的：进一步探讨重型颅脑外伤后继发性呼吸衰竭的发生机制,为临床救治提供实验依据。方法：利用打击伤大鼠模型,用电镜组织化学方法观察额顶叶打击伤后大鼠延髓超微结构及细胞内Ｃａ＾２＋积聚的改变,及尼莫通（Ｎｉｍ）、地寒米松的干预作用。结果：打击伤使延髓细胞内Ｃａ＾２＋积聚增加,Ｃａ＾２＋积聚以胞浆、线粒体及髓鞘为主,细胞超微结构破坏;重伤组较轻伤组变化明显;Ｎｉｍ可明显减少伤后细胞内Ｃａ＾２＋积聚,并能改善细胞器的损伤。结论：重型颅脑外伤导致延髓细胞Ｃａ＾２＋超载可能是继发性呼吸衰竭的发生原因之一,Ｎｉｍ通过减少细胞内Ｃａ＾２＋积聚有一定的治疗作用。     

提高平均动脉压对猪心肺复苏后脑功能及超微结构的影响

目的 探讨使用去甲肾上腺素提高平均动脉压(MAP)对心肺复苏(CPR)猪脑功能及超微结构的影响.方法 10头猪致心室纤颤(室颤)4min后行CPR及电除颤.将自主循环恢复(ROSC)的猪按随机数字表法分为两组:高灌注组5头以去甲肾上腺素升压,使MAP升至麻醉前基础状态的130%;正常灌注组5头以去甲肾上腺素维持MAP至麻醉前状态.另取2头猪作为假手术组,既不给予室颤、也不给予CPR.持续监测血流动力学指标;ROSC后24 h进行大体神经功能分类(OPC),然后处死动物取缺血敏感部位脑组织(大脑皮质、海马CA1区、小脑皮质、纹状体)进行组织缺失评分(HDS)及细胞凋亡计数[原位末端缺刻标记法(TUNEL)];同时在电镜下观察上述部位脑细胞的超微结构.结果 高灌注组5头猪均有较好的神经功能评分(OPC 1～2分);正常灌注组5头中只有3头获得较好神经功能评分(OPC 1～3分).假手术组各部位脑组织基本正常;高灌注组大脑皮质及海马CA1区HDS(分)明显好于正常灌注组(大脑:1.6±0.5比2.2±0.8,海马:1.8±0.8比2.8±0.5,均P＜0.05);小脑皮质及海马CA1区凋亡细胞(个)较正常灌注组明显减少(小脑:21.2±3.2比38.6±3.8,海马:22.7±7.6比35.0±6.8,均P＜0.05).电镜下观察,坏死神经元主要位于大脑皮质、纹状体及海马CA1区,而凋亡主要发生于小脑颗粒细胞及海马CA1区神经胶质细胞.高灌注组神经元损伤明显减轻.结论 使用去甲肾上腺素提高灌注压可以有效减轻脑损伤,并抑制脑组织细胞凋亡.     

Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs.

The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. Daily for 3 weeks, the pigs received 200 mg of itraconazole orally at the beginning of each meal, and for the following 2 weeks they received itraconazole orally combined with intravenous administration of rifampin at 10 mg/kg/day. Coadministration of rifampin resulted in an 18-fold decrease in the maximum concentration of itraconazole in serum, from 113.0 (standard deviation [SD] 17.2) to 6.2 (SD, 3.9) ng/ml and a 22-fold decrease in the area under the concentration-time curve, from 1,652.7 (SD, 297.7) to 75.6 (SD, 30.0) ng.h/ml. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin affects itraconazole kinetics considerably at steady state in this miniature-pig model, probably by inducing hepatic metabolism of itraconazole.     

提高平均动脉压对猪心肺复苏后脑功能及超微结构的影响

Objective To investigate the effects on brain function and ultrastructure changes by elevating mean arterial pressure (MAP) with norepinephrine after cardiopulmonary resuscitation (CPR) in pigs.Methods After 4 minutes of untreated ventricular fibrillation, CPR was begun in 10 piglets, followed by defibrillation.Following the restoration of spontaneous circulation (ROSC), the animals were randomly assigned to two treatment groups: the hypertension group (HT,n = 5), in which animals were given an infusion of norepinephrine to maintain the MAP to 130% above that before ventricular fibrillation, and the normal perfusion group (NP, n=5) who received an infusion of norepinephrine to maintain the MAP to that obtained right after ROSC.Sham-operation group of 2 animals were treated identically, with the exception that neither cardiac arrest was induced nor CPR was performed, to serve as control group.Variables of hemodynamics were measured at baseline and also 4 hours after ROSC.The overall performance categories (OPC) was evaluated 24 hours after ROSC.Then, animals were sacrificed and the brains were removed for histopathological examination of cerebral cortex, CA1 region of hippocampus, cerebellar cortex, and corpus striatum for the assay of histological damage score (HDS), and apoptosis of cerebral neurons were evaluated [terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)]24 hours after ROSC.The ultrastructure of neurons was characterized, using transmission electron microscopy.Results Five animals in the HT group showed good OPC (OPC 1 - 2), while 3 animals in the NP group showed good OPC (OPC 1- 3).Brain tissue from different regions was normal in sham-operation group.The HDS in the cerebral cortex and CA1 region of hippocampus in the HT group was lower than that in the NP group (cerebral cortex: 1.6±0.5 vs.2.2±0.8, hippocampus: 1.8±0.8 vs.2.8±0.5, both P＜0.05).The TUNEL-positive cells in the cerebella and the CA1 region of hippocampus were significantly reduced in the HT group compared with the NP group (cerebella: 21.2±3.2 vs.38.6±3.8, hippocampus: 22.7±7.6 vs.35.0 ± 6.8, both P＜0.05).With transmission electron microscopy, necrotic neurons were found in the cerebral cortex, striatum and the CA1 region of hippocampus, while in cerebella only granular cells and glial cells in the CA1 region of hippocampus showed apoptosis.The damages to neurons were significantly reduced in HT group.Conclusion Hypertension induced by norepinephrine is a safe and effective method to reduce brain damages and prevent apoptosis of neurons.     

Pharmacokinetic interaction between itraconazole and ceftriaxone in Yucatan miniature pigs.

Since ceftriaxone and itraconazole are highly protein bound, are excreted via a biliary pathway, and are in vitro modulators of the efflux pump P glycoprotein, a pharmacokinetic interaction between these antimicrobial agents can be hypothesized. Therefore, we evaluated the pharmacokinetics of itraconazole and ceftriaxone alone and in combination in a chronic model of catheterized miniature pigs. Itraconazole does not influence ceftriaxone kinetic behavior. The mean areas under the concentration-time curve (AUC) were 152.2 microg x h/ml (standard deviation [SD], 22.5) and 129.2 microg x h/ml (SD, 41.2) and the terminal half-lives were 1.1 h (SD, 0.3) and 0.9 h (SD, 0.2) when ceftriaxone was given alone and combined with itraconazole, respectively. Regarding itraconazole kinetics, ceftriaxone was shown to alter the disposition of the triazole. Contrary to what was expected, the AUC (from 0 to 8 h) decreased from 139.3 ng h/ml with itraconazole alone to 122.7 ng h/ml with itraconazole and ceftriaxone combined in pig 1, from 398.5 to 315.7 ng x h/ml in pig 2, and from 979.6 to 716.6 ng x h/ml in pig 3 (P of <0.01 by analysis of variance).