盐酸纳洛酮治疗大鼠急性颅脑损伤的药效学观察

目的观察盐酸纳洛酮(金尔伦)在大鼠急性颅脑损伤实验模型中促进神经功能恢复的治疗作用,并做量效分析。方法SD大鼠250只,采用Feenly自由落体撞击法建立颅脑损伤模型,随机分成六组,于损伤后30min开始给药。前四组每天分别给予金尔伦0.3mg/kg、1mg/kg、3mg/kg和9mg/kg腹腔注射;阳性对照组:给予胞磷胆碱钠2mg/只腹腔注射;阴性对照组:给予0.5ml/只生理盐水腹腔注射。每天进行MNSS神经功能评分,最长疗程为14d。伤后2d和4d每组随机取8只大鼠,通过干—湿重法计算脑组织的含水量。结果金尔伦治疗组大鼠的神经功能恢复情况明显优于其他两组(P<0.01)。金尔伦1、3、9mg/kg三组的情况优于0.3mg/kg组(P<0.05),而这三组之间没有显著性差异(P>0.05)。金尔伦治疗组大鼠的脑含水量明显低于对照组(P<0.05);金尔伦内部各实验组之间,0.3mg/kg组的脑含水量高于其他三组(P<0.05),其他三组之间无显著性差异(P>0.05)。结论金尔伦能够降低大鼠急性颅脑损伤后的脑水肿,对大鼠的神经功能恢复有明显的促进作用,并在一定范围内随着剂量的增加效果更显著。     

金尔伦(盐酸纳洛酮)对重型头伤后脑组织内Ca~(2 )、Mg~(2 )、EAA及血浆ET变化影响与意义

目的　探讨金尔伦 (盐酸纳洛酮 )对重型头伤后脑组织内Ca2 、Mg2 、EAA及血浆ET变化的影响及临床意义。方法　SD大鼠 72只 ,随机分为治疗组、对照组及空白组。参照Feeny自由落体撞击法建立头伤模型 ,伤后半小时 ,治疗组大鼠于腹腔注射金尔伦 10mg/kg;对照组大鼠则于腹腔注射生理盐水 10mg/kg ;空白组不作任何处理。按伤后处理时间各组再分为 4小组 ,每组 6只 ,分别于伤后 1小时 ,2小时 ,4小时 ,8小时处死 1小组 ,检测损伤区脑组织内Ca2 、Mg2 、EAA及ET含量。结果　治疗组伤后Ca2 、EAA和ET含量轻度升高 ,Mg2 含量下降不明显 ,与对照组相比有统计学差异。结论　金尔伦通过竞争性拮抗内源性阿片肽受体 ,能明显逆转实验动物重型头伤后损伤区脑组织内Ca2 、EAA和ET含量的增高及Mg2 的下降 ,具有脑保护作用。其详细机理有待进一步研究。     

纳洛酮治疗急性重型颅脑损伤的量效关系

目的观察盐酸纳洛酮治疗急性重型颅脑损伤病人的剂量疗效关系。方法将120例急性重型颅脑损伤病人随机分为6组(空白对照组以及0.1、0.2、0.4、0.6、0.8 mg.kg-1.d-1纳洛酮组),分别给予生理盐水及相应分组剂量纳洛酮,观察GCS、血压、脉搏、呼吸等生命体征,测定血浆β-内啡肽(-βEP)和C-反应蛋白(CRP)含量。随访3个月,观察GOS、肢体和语言功能评分。结果GCS、β-EP、CRP在小剂量纳洛酮组(0.1 mg.kg-1.d-1)与对照组间差异无统计学意义;大剂量纳洛酮组各组间(≥0.4 mg.kg-1.d-1)差异无统计学意义,但与空白对照组、小剂量组、中剂量组(0.2 mg.kg-1.d-1)间差异有统计学意义。血压、脉搏、呼吸在纳洛酮各组间差异无统计学意义,但与对照组间差异有统计学意义。随访3个月,GOS、肢体功能及语言功能评分在大剂量组与对照组、小剂量组、中剂量组之间的差异有统计学意义,且小剂量组恢复最差(P<0.05);但大剂量各组之间的差异无统计学意义结论①盐酸纳洛酮(≥0.2 mg.kg-1.d-1)对急性重型颅脑损伤有显著的治疗作用,能促进神经功能的恢复;②小剂量盐酸纳络酮(≤0.1 mg.kg-1.d-1)对颅脑损伤后的神经功能保护无意义,临床不提倡使用;③盐酸纳络酮剂量0.4～0.6 mg.kg-1.d-1为最佳临床推荐剂量。     

静脉注射结合脑室内部灌注金尔伦（盐酸纳洛酮）治疗重型颅脑损伤

本文报告在静脉滴注盐酸纳洛酮 (金尔伦 ) 4mg/d的基础上 ,于手术时在脑损伤创面上灌注金尔伦 4mg ,此后每隔 8小时向脑室内灌注金尔伦 7～ 10mg ,取得了较好疗效。纳洛酮为脂溶性 ,易透过血脑屏障 ,脑外伤后血脑屏障通透性增加 ,药物更易通过血脑屏障 ,因此有无必要在脑损伤局部及脑室内灌注金尔伦需行进一步研究 ,应有充分证据说明局部或脑室内用药优于静脉内给药。文献报告 (BehavNeurosci,2 0 0 0 ,114 :1183 1190 .DevPsychobiol,2 0 0 0 .3 7:12 9 14 3 .) 向动物脑室内、枕大池或鞘内灌注纳洛酮未引起不良反应。但在临床应用中还需慎重考虑用药途径 ,以免误导 ,造成不良反应事件。     

金尔伦(盐酸纳洛酮)治疗急性中、重型脑外伤的神经电生理研究

目的：通过诱发电位（EP）监测,探讨金尔伦（盐酸纳洛酮）治疗急性中,重型脑外伤的疗效,方法：对40例急性中,重型脑外伤患者者随机,双盲治疗,前3天剂量为每日0．3mg/kg,后7天剂量为4.8mg/日,于用药前,用药后30分钟,24小时,72小时,120小时监测正中神经短潜伏期体感诱发电位（SLSEP）和脑干听觉诱发电位（BAEP）,揭盲后分为金尔伦治疗组和对照组,对金氽伦治疗组与对照组诱发电位进行统计学分析,结果：金尔伦治疗级SLSEP的N13－N20峰间潜伏期（N13－N20IPL）及BAEP的I－V波峰间潜伏期（I－VIPL）在用药手均较对组缩短且有显著性差异,P＜0．05,结论,诱发电位监测结果表明,金尔伦能有效改善急性脑外伤患者异常的神经网络生理指标,对于急性中,重型脑外伤有明显的治疗作用。     

金尔伦（盐酸纳洛酮）对重型头伤后脑组织内Ca^2＋、Mg^2＋、EAA及血浆ET变化影响与意义

目的：探讨金尔伦（盐酸纳洛酮）对重型头伤后脑组织内Ca^2 ,Mg^2 ,EAA及血浆ET变化的影响及临床意义,方法：DS大鼠72只,随机分为治疗组,对照组及空白组,参照Feeny自由落体撞击法建立头伤模型,伤后半小时,治疗组大鼠于腹腔注射金尔伦10mg/kg,对照组大鼠则于腹腔注射生理盐水10mg/kg,空白组不作任何处理,按伤后处理时间各组再分为4小组,每组6只,分别于伤后1小时,2小时,4小时,8不时处死1小组,检测缶伤区脑组织内Ca^2 ,Mg^2 ,EAA及ET含量,结果,治疗组伤后Ca^2 ,EAA和ET含量轻度升高,Mg^2 含量不和不明显,与对照组相比有统计学差异。结论：金尔伦通过竞争性拮抗内源性阿片肽受体,能明显逆转实验动物重型头伤后损伤区脑组织内Ca^2 ,EAA和ET含量的增高及Mg^2 的下降,具有脑保护作用,其详细机理有待进一步研究。     

替米沙坦对局灶性脑缺血再灌注大鼠c-fos表达和神经保护

目的 研究不同剂量血管紧张素I受体拮抗剂替米沙坦对大鼠脑缺血再灌注的神经保护作用.方法 60只大鼠随机分为4组,假手术组、生理盐水对照组、小剂量替米沙坦治疗组2 mg/(kg·d)、大剂量替米沙坦治疗组10 mg/(kg·d).通过线栓法制作大鼠大脑中动脉缺血再灌注模型(MCAO),记录神经功能缺损评分、监测血压、梗死面积、c-fos的表达.结果 小剂量替米沙坦组平均动脉压较对照组适度下降,大剂量组则较为剧烈.小剂量替米沙坦组脑梗死体积小于对照组(P<0.05),而大剂量组与对照组相比变化不大(P>0.05).各组大鼠神经功能随时间推移逐渐恢复,但各组恢复程度不同,治疗组较对照组神经功能恢复明显较好(P<0.05).c-fos的表达随损伤好转逐渐降低,应用替米沙坦干预后c-fos表达较对照组减少,且小剂量替米沙坦组减少更明显.结论 小剂量替米沙坦可以提供降低血压之外的神经保护作用,其机制可能为减少c-fos表达,抑制缺血损伤后神经凋亡.大剂量替米沙坦无明显神经保护作用.     

大剂量纳洛酮治疗急性脑梗死临床研究

目的 观察早期应用大剂量纳洛酮对脑梗死治疗的有效性及安全性.方法 106例脑梗死患者随机分成大剂量纳洛酮治疗组(n=54)和常规剂量纳洛酮对照组(n=52),治疗组给予纳洛酮4mg/d,而对照组1.2mg/d,2周一疗程,进行神经功能缺损评分,观察症状改善时间.结果 治疗组神经功能改善,总有效率88.89%,明显高于对照组的73.07%(P<0.05),而且治疗组24h内症状改善24.07%,明显好于对照组的13.46%(P<0.05).结论 早期大剂量纳洛酮治疗急性脑梗死,能显著减轻神经功能损伤而且无明显不良反应.     

金尔伦(盐酸纳洛酮)治疗急性颅脑损伤病人随机双盲多中心前瞻性临床研究

背景：本试验是由中华医学会神经外科学会和中华神经外科杂志部组织，国内18家医院实施，完成金尔伦（盐酸纳洛酮）对受试患者的疗效和用药安全性观察，目的，证明金尔伦在治疗急性中，重型颅脑损伤患者的治疗和安全性，方法：设计并实施了随机双盲前瞻性临床对照试验计划，比较大剂量金尔伦和生理盐水安慰剂的疗效差异，每位受试得接受为期10天随机分组治疗和3个月随访，分析对比治疗前后和治疗过程中患者的病情和重要辅助检查指标的变化,趋势并同时对比随访结束时患者神经功能恢复情况和生活质量状况，全部试验结束后进行揭盲并对结果进行统计学分析,结果，实际完成530例，有效病例511例，其中金尔伦组256例，安慰剂组255例，金尔伦组和安慰剂组死亡率分别为治疗组12．5％，有效病例12．5％，安慰剂组17．3％（P＜0．05），金尔伦组患者GCS评分在用药后第5天开始明显优于安慰剂组（P＜0．05），治疗结束后金尔伦组患者GOS评分明显优于安慰剂组（P＜0．05），金尔伦组患者语言功能评分和生活质量状况评分也明显优于安慰剂组（P＜0．05），另外，过程中未发现因用药造成的毒副反应，结论：早期应用大剂量金尔伦能明显降低急性颅脑损伤患者死亡率，促进脑神经功能恢复，改善远期生活质量状况，并且具有相当可靠的安全性。     

早期大剂量纳洛酮联合醒脑静治疗大面积脑梗死32例

目的 研究早期大剂量纳洛酮联合醒脑静治疗24 h内未经溶栓的大面积脑梗死患者的临床疗效.方法 观察组采用盐酸纳洛酮注射液4mg·d-1·次-1联合醒脑静注射液20 mL·d-2,连用1周;纳洛酮组(纳洛酮注射液4 mg·d-1·次-1,连用1周)醒脑静组(醒脑静注射液20 mL·d-2,连用1周)观察治疗前后意识障碍恢复情况.结果 治疗组总有效率达90.63％,明显高于纳洛酮组的59.37％及醒脑静组的62.50％(x2=8.33,P＜0.01;x2=7.05,P＜0.01).结论 早期大剂量纳洛酮联合醒脑静治疗大面积脑梗死疗效确切,能明显提高意识障碍恢复时间.     

Optimal compatible doses and effects of ephedrine and naloxone on neural plasticity in cerebral ischemia/reperfusion rats

BACKGROUND： Ephedrine promotes neural plasticity in rats following cerebral ischemia/reperfusion injury. Ephedrine has been combined with naloxone in some studies, and it has been confirmed that their combination has synergistic effects on increasing neural plasticity following cerebral ischemia/reperfusion injury. OBJECTIVE： To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity and to find an optimal dose of naloxone in rats after cerebral ischemia/reperfusion injury by analyzing growth associated protein-43 （GAP-43）, synaptophysin and β-endorphin expression in the hippocampal CA3 area. DESIGN, TIME AND SETTING： This immunohistochemical, randomized, controlled, animal experiment was performed at the Chongqing Research Institute of Pediatrics, China from September 2007 to June 2008. MATERIALS： Ephedrine hydrochloride injection and naloxone hydrochloride injection were respectively purchased from Shandong Lvliang Pharmaceutical Factory, China and Sichuan Jingwei Pharmaceutical Co., Ltd., China. A total of 192 healthy adult Sprague Dawley rats were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. METHODS： At 2 hours following cerebral ischemia, the rats were intraperitoneally injected with 1.5 mg/kg/d ephedrine （ephedrine group）, with 0.1, 0.2, or 0.3 mg/kg/d naloxone （low, moderate and high doses of naloxone groups）, with 1.5 mg/kg/d ephedrine ＋ 0.1, 0.2, or 0.3 mg/kg/d naloxone （ephedrine ＋ low, moderate and high doses of naloxone groups）, and with 0.5 mL saline （model group）, respectively. MAIN OUTCOME MEASURES： GAP-43, synaptophysin and β -endorphin expression were detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery. Sensorimotor integration in rats was assessed using the beam walking test. RESULTS： GAP-43 and synaptophysin expression was greater in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups co     

纳络酮早期干预对大鼠弥漫性轴索损伤的影响

目的观察纳络酮早期干预对大鼠实验性弥漫性轴索损伤(DAI)的治疗效果。方法采用改良Marmarou的方法制作大鼠颅脑DAI模型。将Wister雄性大鼠99只随机分为对照(假损伤)组、损伤组和干预组,干预组用纳络酮2mg/kg于伤后45min腹腔一次性注射给药,于伤后2、6、24、72h观察动物行为、脑组织含水量及组织病理学变化。结果损伤组大鼠伤后2、6、24、72h,行为学评分(满分为21.00±0.00分)分别为(9.05±1.52)、(12.12±1.41)、(17.23±1.34)和(19.36±0.92)分;干预组各时间点分别为(9.32±1.23)、(14.48±1.54)、(18.68±1.09)和(20.18±0.75)分;其中干预组伤后6和24h与损伤组比较差异显著(P0.05)。对照组24h脑组织含水量测定结果为(78.19±0.35)%;伤后2、6、24、72h脑组织含水量,损伤组分别为(79.91±0.18)%、(80.70±0.49)%、(81.69±0.40)%和(80.32±0.42)%;干预组分别为(79.22±0.33)%、(79.59±0.46)%、(80.44±0.49)%和(79.50±0.44)%。同损伤组比较,干预组致伤6h后脑含水量均明显减轻(P0.01)。干预组光镜下病理损害明显减轻。结论纳络酮伤后早期干预,有助于减轻大鼠DAI后继发性脑损害。     

钙通道阻滞剂对大鼠坐骨神经损伤后c-fos表达及神经功能的影响

目的探讨钙通道阻滞剂(CCB)对周围神经损伤后c-fos表达及神经功能的影响。方法制作坐骨神经嵌压性损伤大鼠模型,给予模型大鼠分别腹腔注射氟桂利嗪1mg/kg(低剂量组)、2mg/kg(高剂量组),或生理盐水10ml/kg(模型组)。在坐骨神经嵌压后第1周、第4周时取大鼠坐骨神经,采用免疫组织化学、行为医学和电生理学的方法测定c-fos阳性细胞数及第4周时足趾间距、神经传导速度(NCV);并与正常大鼠比较。结果(1)损伤后1周时,模型组、氟桂利嗪低剂量组坐骨神经c-fos阳性细胞数显著多于正常对照组(均P<0.01);氟桂利嗪高剂量组c-fos阳性细胞数轻度增加,也显著多于正常对照组(P<0.05),但明显少于模型组和氟桂利嗪低剂量组(均P<0.01);损伤4周时各组c-fos阳性细胞数均无明显增高。(2)损伤后4周时,模型组和氟桂利嗪低剂量组、高剂量组坐骨神经NCV显著慢于正常对照组(均P<0.01),氟桂利嗪低剂量组、高剂量组的NCV快于模型组(P<0.05,P<0.01)。(3)损伤后4周时,模型组大鼠右后肢足趾间距明显小于其他3组(均P<0.01);氟桂利嗪高剂量组、低剂量组与正常对照组比较差异无统计学意义(均P>0.05)。结论CCB使周围神经损伤后早期c-fos表达下调,并使神经功能受损减轻。     

Bacitracin produces analgesia by increasing brain immunoreactive ß-endorphin (ß-E) content

The effects of protease inhibitor bacitracin on brain ß-endorphin content and analgesia, were examined in vivo. Male Sprague-Dawley rats were injected with bacitracin intracerebroventricularly and sacrificed by microwave irradiation 15 and 30 min after injection. Brain ß-endorphin levels were 27% higher in bacitracin treated rats than in controls. A second group of bacitracin injected rats was subjected to continuous intermittent 55 °C hot plate exposure. Bacitracin-injected rats exhibited total analgesia 15 min after bacitracin injection. At 30 min, this analgesic effect subsided. Control rats exhibited no analgesia. Bacitracin induced analgesia was naloxone reversible at a low dose of naloxone (1 mg/kg). At a higher dose of naloxone (10 mg/kg), bacitracin induced analgesia was only partially antagonized. These results suggest that bacitracin induced analgesia might be due to the elevated levels of brain ß-endorphin caused by a decrease in its breakdown by bacitracin.     

Interleukin-1 receptor antagonist attenuates regional neuronal cell death and cognitive dysfunction after experimental brain injury.

The effect of systemic administration of human recombinant interleukin-1 receptor antagonist (rhIL-1ra) on behavioral outcome and histopathologic damage after lateral fluid-percussion brain injury of moderate severity was evaluated. In study 1, brain-injured Sprague Dawley rats received timed subcutaneous injections beginning 15 minutes after injury of either 100 mg/kg rhIL-1ra (high dose, total dose = 1900 mg/kg), 10 mg/kg rhIL-1ra (low dose, total dose = 190 mg/kg), or vehicle over 7 days. No effect of low-dose rhIL-1ra was observed in study 1. High-dose rhIL-1ra significantly attenuated posttraumatic neuronal loss in the injured hippocampal CA3 region (P < 0.05), dentate hilus (P < 0.05), and cortex (P < 0.05) but impaired recovery of motor function at 7 days after trauma (P < 0.05). In study 2, rats were pretrained to learn a visuospatial task in a Morris water maze, subjected to fluid-percussion brain injury or sham treatment, and randomly assigned to receive multiple subcutaneous injections at timed intervals of 100 mg/kg rhIL-1ra (total dose = 900 mg/kg) or vehicle over 42 hours, followed by continuous infusion of a lower concentration of rhIL-1ra (20 mg/kg/day, total dose = 100 mg/kg), or vehicle for 5 days using subcutaneously implanted osmotic minipumps. Postinjury administration of rhIL-1ra significantly attenuated cognitive deficits compared with vehicle-treated animals at 42 hours (P < 0.05) but did not affect motor function at 48 hours, 1 week, and 2 weeks. These results suggest that inhibitors of cytokine pathways may be therapeutically useful for the treatment of brain trauma.     

TRH analog YM-14673 improves outcome following traumatic brain and spinal cord injury in rats: dose-response studies

YM-14673 is a thyrotropin-releasing hormone (TRH) analog that has a modification of the N-terminal (pyroglutamyl) moiety of the tripeptide. It is longer acting than TRH and has substantially greater potency with regard to central facilitatory activity. In the present studies, the effect of YM-14673 was examined in rats following standardized traumatic brain or spinal cord injury. Pentobarbital-anesthetized animals were subjected to fluid-percussion-induced brain trauma to the parietal cortex or impact trauma to the thoracic spinal cord. After injury animals were randomly assigned to treatment with i.v. YM-14673 at varying doses--0.1 mg/kg (low), 1.0 mg/kg (moderate), or 10 mg/kg (high)--or equal volume physiological saline. Treatment with YM-14673 improved chronic neurological recovery after trauma in both injury models; optimal beneficial effects were found at a dose of 1.0 mg/kg. These findings confirm previous observations that TRH or TRH analogs may improve outcome after traumatic brain and spinal cord injury and are consistent with the hypothesis that TRH analogs preserving the C-terminus are effective in CNS trauma.     

Amino acid incorporation during morphine intoxication. I: Dose and time effects of morphine on protein synthesis in specific regions of the rat brain and in astroglia-enriched primary cultures

Uptake and incorporation of 3H-valine into soluble protein were studied in normal and in physically dependent rat brain, or in astroglial primary cultures at various times after the administration of morphine at different doses. There was an increased protein synthesis in striatum and brain stem of previously untreated rats 2-3 hr after low-dose morphine administration (10 mg/kg bw IP). The changes were completely reversed by naloxone (5 mg/kg bw, IP) administered 10 min prior to the morphine. During the first hour after IP administration of 25 mg morphine/kg bw there was a decrease in striatum and brain stem protein synthesis, followed by an increase in brain stem protein synthesis between 2 and 3 hr later. These changes were blocked by naloxone. In all brain regions studied 40 mg morphine/1 kg bw, IP inhibited protein synthesis, an effect partially reversed by naloxone (5 mg/kg bw, IP). Similar dose- and time-dependent effects were obtained from primary astroglia-enriched cultures from cerebral hemispheres, suggesting that low or moderate doses of morphine affect brain cell protein synthesis. At least one phase of increased synthesis was seen, but within a few hours of a high morphine dose the protein synthesis was decreased. After long-term morphine intoxication (13 days; final dose 340 mg/kg bw/day po) incorporation of 3H-valine in vivo into TCA-precipitable soluble proteins during 60 min decreased in the hypothalamus and in the occipital and entorhinal cortex, and was unchanged in other brain regions examined. An IP injection of morphine (10 or 25 mg/kg bw/day) to such animals resulted in a pronounced and rapidly occurring increase in protein synthesis in many brain regions. This was further demonstrated with gel electrophoresis in brain stem and hypothalamus, where higher 3H-labeling was seen in many protein bands. The labeling of one band from brain stem having approx 80,000 MW was especially pronounced. Incorporation of 3H-valine into membrane-bound proteins of brain stem changed in a similar way to the soluble proteins, but was not as pronounced.     

Preventive effects of dexamethasone on hypoxic-ischemic brain damage in the neonatal rat

To clarify the preventive effects of glucocorticoid on perinatal hypoxic-ischemic (HI) brain damage, an experiment was carried out on 4-day-old rats pretreated for 4 consecutive days with 3 different regimens; namely, a low dose dexamethasone (Dex) (0.1 mg/kg/day), a high dose Dex (0.5 mg/kg/day), and a saline administration. On the 7th postnatal day, after ligation of the left common carotid artery, the rats were exposed to 8% oxygen and decapitated on the 10th, 14th, 21st and 28th postnatal days. Ligated side brain damage was observed in 75, 7 and 3% of the rats in the saline, low and high dose Dex groups, respectively. However, a high mortality rate (42%) was noted in the high dose Dex group. The cumulative number of animals with poor outcome (death or brain damage) was 49 (80%), 13 (33%) and 24 (44%) in the saline, low and high dose Dex groups, respectively. On the 10th and 14th postnatal days, the rats in both the Dex groups showed delayed neuronal maturation and myelination in the non-ligated side motor cortex, however, these maturational differences disappeared on the 21st postnatal days. Otherwise, the number of cortical cells in both the Dex groups were significantly lower than that in the saline group on the 28th postnatal days (P < 0.05 in each). These findings suggest that the pretreatment with Dex protects the developing brain from HI injury through the suppression of the neuronal maturation. However, a decreased number of cortical cells may give rise to psychomotor retardation later.     

α-硫辛酸对糖调节受损大鼠认知功能和氧化应激影响的初步研究

目的研究硫辛酸对糖调节受损大鼠认知功能和氧化应激的影响。方法雄性Wistar大鼠随机分为5组,对照组、模型组、硫辛酸低[15 mg/(kg·d)]、中[30 mg/(kg·d)]、高[60 mg/(kg·d)]剂量组。用高脂高糖饲料饲养法建立糖调节受损大鼠模型,给予成功的大鼠模型连续每日灌胃硫辛酸溶液15 mg/kg、30 mg/kg、60 mg/kg,每日一次,共14 d。用Morris水迷宫法检测大鼠学习记忆能力;用流式细胞仪检测各组大鼠海马组织的ROS含量值。结果与对照组相比,模型组大鼠学习记忆能力下降(P0.05),海马组织内ROS水平升高(P0.05);与模型组相比,硫辛酸组脑内ROS水平下降,大鼠的学习和记忆能力提高,尤以中剂量组改变明显(P0.05)。结论α-硫辛酸对糖调节受损大鼠的认知功能有保护作用,该保护作用与其抗氧化作用有关。     

Effects of scopolamine treatment on long-term behavioral deficits following concussive brain injury to the rat

Scopolamine (0.1, 1.0, or 10.0 mg/kg) or saline was systemically (i.p.) administered to rats 15 min prior to concussive fluid percussion brain injury. Animals pretreated with the 1.0 mg/kg dose exhibited significantly (P less than 0.05) less motor deficits and less body weight loss and recovered to baseline performance sooner than saline-treated rats. Mortality and associated convulsions were significantly lower in rats pretreated with the 1.0 mg/kg dose of scopolamine. A 1.0 mg/kg dose of scopolamine administered (i.p.) 30 s after injury also significantly reduced behavioral deficits. No differences were observed between saline- and scopolamine-treated animals in either the incidence or duration of transient apnea following injury. A 1.0 mg/kg dose of scopolamine administered (i.p.) 15 min prior to epidural clip compression of the spinal cord had no effect on the severity of motor function deficits assessed by an inclined plane test. The data from these experiments suggest muscarinic cholinergic involvement in at least some of the long-term behavioral deficits following mild and moderate levels of brain injury. These results suggest that muscarinic cholinergic antagonists may prove beneficial in the treatment of human head injury.