盐酸戊乙奎醚对大鼠曲马多依赖及相关脑区c-fos、△FosB及M5受体表达的影响

目的 探讨盐酸戊乙奎醚对大鼠曲马多依赖及相关脑区c-fos、△FosB及M5受体表达的影响.方法 雄性成年SD大鼠30只,体重180～220 g,采用随机数字表法,将其随机分为3组(n=10):对照组(C组)、曲马多依赖组(T组)和盐酸戊乙奎醚组(P组).T组和P组连续7d交替皮下注射曲马多10mg/kg(9:00)或生理盐水(16:00),诱导大鼠曲马多条件性位置偏爱效应.实验第8天停用曲马多,P组腹腔注射盐酸戊乙奎醚1.5 mg/kg,C组及T组腹腔注射等量生理盐水,30 min后行条件性位置偏爱实验,记录大鼠伴药区停留时间.条件性位置偏爱实验结束后处死大鼠,取出大脑,分离相关脑区(中脑腹侧被盖区、前额叶皮层、伏隔核),采用Western blot法检测c-fos、△FosB蛋白的表达,RT-PCR法检测M5受体mRNA的表达水平.结果 与C组比较,T组伴药区停留时间延长,c-fos、△FosB蛋白和M5受体mRNA表达上调,P组M5受体mRNA和△FosB蛋白表达下调(P＜0.05或0.01),伴药区停留时间和c-fos蛋白表达水平差异无统计学意义(P＞0.05);与T组比较,P组伴药区停留时间缩短,c-fos和△FosB蛋白和地M5受体mRNA表达下调(P＜0.01).结论 盐酸戊乙奎醚可减轻大鼠曲马多依赖,其机制可能与下调相关脑区c-fos、△FosB蛋白和M5受体基因表达有关.     

盐酸戊乙奎醚对吗啡依赖大鼠相关脑区p-CREB及M5受体的影响

目的 观察盐酸戊乙奎醚(PHC)对吗啡依赖大鼠相关脑区p-CREB及M5受体的影响.方法 将雄性SD大鼠30只随机分为对照组(NS组)、吗啡依赖组(MOR组)和PHC治疗组(PHC组),每组10只.连续7d交替皮下注射吗啡(10 mg/kg,每天1次)或生理盐水,诱导大鼠的吗啡依赖位置偏爱效应.实验第8天停用吗啡,NS组与MOR组腹腔注射等体积的生理盐水;PHC治疗组则腹腔注射PHC 1.5 mg/kg.30 min后各组大鼠行CPP测试.Western blot法检测大鼠中脑腹侧被盖区、伏隔核、前额叶皮层p-CREB的蛋白表达;实时定量聚合酶链反应(PCR)检测大鼠中脑腹侧被盖区、伏隔核、前额叶皮层M5受体的mRNA水平.结果 (1)PHC治疗组的灰区停留时间与MOR组比较显著缩短[(422±103)s 比(622 ±97)s,P＜0.01].(2)MOR组中脑腹侧被盖区、伏隔核、前额叶皮层组织中p-CREB水平显著高于NS组[(0.93±0.06)、(0.67±0.10)、(0.89±0.14)比(0.31±0.02)、(0.20±0.01)、(0.40±0.07),P＜0.01];与MOR组比较,PHC组中脑腹侧被盖区、伏隔核、前额叶皮层组织中p-CREB水平显著降低[(0.65±0.05)、(0.58±0.04)、(0.67±0.09),P＜0.05或P＜0.01].(3)MOR组中脑腹侧被盖区、伏隔核、前额叶皮层组织中M5受体的mRNA含量较NS组显著增高(1.80、0.22、0.50比1.00、0.13、0.32,P＜0.01);与MOR组比较,PHC 组能明显降低中脑腹侧被盖区、伏隔核、前额叶皮层组织中M5的mRNA含量(0.65、0.09、0.07,P＜0.01).结论 PHC能抑制吗啡依赖大鼠条件性位置偏爱的表达,该效应可能与PHC下调中脑腹侧被盖区、伏隔核、前额叶皮层组织中M5受体,抑制p-CREB表达有关.     

粒细胞集落刺激因子对大剂量盐酸戊乙奎醚所致大鼠认知功能障碍的影响

目的观察粒细胞集落刺激因子(G-CSF)对大剂量盐酸戊乙奎醚所致大鼠认知功能障碍的影响。方法 24只14个月龄Wistar成年雄性大鼠随机分为三组:空白组(N组)、盐酸戊乙奎醚组(P组)和G-CSF治疗组(G组),每组8只。N组腹腔注射生理盐水1ml,P组腹腔注射盐酸戊乙奎醚2.56mg/kg,G组腹腔注射盐酸戊乙奎醚2.56mg/kg后皮下注射G-CSF 50μg/kg,连续5d。第1、3、5天给药后用Morris水迷宫测试其空间学习记忆能力的改变,末次水迷宫实验后用免疫组化法观察海马胆碱乙酰转移酶(ChAT)阳性细胞表达个数。结果与第1天比较,第3天和第5天三组潜伏期和游泳距离均明显缩短(P<0.05),且第5天N组和G组明显短于P组(P<0.05)。与P组比较,N组和G组海马区ChAT阳性细胞个数均明显增多(P<0.05)。结论 G-CSF可以改善大剂量盐酸戊乙奎醚引起的大鼠认知功能障碍。     

盐酸戊乙奎醚对野百合碱致大鼠肺动脉高压的抑制作用

目的探讨盐酸戊乙奎醚是否能够减缓野百合碱导致的大鼠肺动脉高压及是否能够预防或缓解肺血管重构。方法 3~4周龄健康雄性SD大鼠30只,体重90~100g,随机均分为正常对照组(C组)、野百合碱肺高压组(M组)、盐酸戊乙奎醚组(P组),每组10只。M组和P组腹腔注射野百合碱60mg/kg建造大鼠肺动脉高压模型,C组腹腔注射等容量生理盐水。P组大鼠于建模前15min时腹腔注射盐酸戊乙奎醚2mg/kg,建模第2天腹腔注射盐酸戊乙奎醚1mg/kg,C组和M组在相应时点腹腔注射等容量生理盐水,连续使用3周。在建模后第21天,三组大鼠检测血流动力学(肺动脉压、右心室压);处死大鼠前采集静脉血以备血液生化检测:ELISA法检测一氧化氮(NO)含量、内皮素-1(ET-1)含量。处死大鼠后留取左肺组织行病理切片以观察肺组织病理形态学变化,取右肺组织于-80℃冻存以备后续检测。结果 M组和P组右心室SBP、平均肺动脉压、肺动脉SBP和肺动脉DBP明显高于C组(P0.05);P组右心室SBP、平均肺动脉压、肺动脉SBP和肺动脉DBP明显低于M组(P0.05)。M组肺小动脉明显增厚,肺小动脉管腔狭窄甚至闭塞,肺组织炎性细胞浸润非常明显。P组肺小动脉壁增厚减轻,肺组织炎性细胞浸润减轻。M组大鼠血清中NO含量明显低于,ET-1的含量明显高于C组(P0.05);P组大鼠血清中NO含量明显高于M组和C组(P0.05),ET-1含量明显高于C组,但明显低于M组(P0.05)。结论使用野百合碱成功建造了大鼠肺动脉高压模型,NO含量降低、ET-1含量增加可能与野百合碱致大鼠肺动脉高压的形成有关;盐酸戊乙奎醚减缓野百合碱致大鼠肺动脉高压模型的肺动脉压力的升高、改善肺小动脉壁增厚可能与增加NO含量、降低ET-1含量有关。     

盐酸戊乙奎醚对体外循环致大鼠脑损伤的影响

目的 评价盐酸戊乙奎醚对体外循环(CPB)致大鼠脑损伤的影响.方法 成年雄性SD大鼠30只,随机分为5组(n=6),假手术组(S组)仅进行动脉和静脉穿刺置管,CPB组、低剂量盐酸戊乙奎醚组(PL组)、中剂量盐酸戊乙奎醚组(PM组)和高剂量盐酸戊乙奎醚组(PH组)建立CPB模型,PL组、PM组和PH组分别在预冲液中加入盐酸戊乙奎醚0.2、0.6、2.0 mg/kg,CPB组加入等容量生理盐水.停CPB后2 h采集上腔静脉血样,测定血浆神经元特异性烯醇化酶(NSE)和S-100β蛋白浓度.然后取脑组织,透射电镜下观察海马区神经元的超微结构.结果 与S组比较,其余4组血浆NSE和S-100β蛋白浓度升高(P＜0.05);与CPB组和PL组比较,PH组和PM组血浆NSE和S-100β蛋白浓度降低(P＜0.05);与PM组比较,PH组血浆S-100β蛋白浓度降低(P＜0.05).PH组和PM组海马区神经元损伤程度轻于CPB组和PL组.结论 预充液中加入盐酸戊乙奎醚0.6或2.0 mg/kg可减轻CPB致大鼠脑损伤,且呈剂量依赖性.     

盐酸戊乙奎醚对围体外循环期大鼠肠粘膜屏障功能的影响

目的 探讨不同剂量盐酸戊乙奎醚对围体外循环(CPB)期大鼠肠粘膜屏障功能的影响.方法 雄性sD大鼠30只,体重300～400 g,随机分为5组(n=6):假手术组(S组)、CPB组、高剂量盐酸戊乙奎醚组(PH组)、中剂量盐酸戊乙奎醚组(PM组)和低剂量盐酸戊乙奎醚组(PL组).建立大鼠CPB模型,S组仅置管不转流,PH组、PM组、PL组和CPB组分别在预冲液中加入盐酸戊乙奎醚2、0.6、0.2 mg/kg和等容量生理盐水.停CPB后2 h取大鼠肠系膜上静脉及腔静脉血,测定血浆D-乳酸、内毒素(LPS)浓度和二胺氧化酶(DAO)活性,透射电镜下观察小肠粘膜病理学结果.结果 与S组比较,CPB组、PH组、PM组和PL组血浆D-乳酸、LPS浓度和DAO活性升高(P＜0.05);与CPB组比较,PH组和PM组血浆D-乳酸、LPS浓度和DAO活性降低(P＜0.05);与PL组比较,PM组和PH组血浆DAO活性、D-乳酸和LPS浓度降低(P＜0.05);与PM组比较,PH组血浆DAO活性和D-乳酸浓度降低(P＜0.05).PH组和PM组小肠上皮病理损伤程度较CPB组和PL组明显减轻.结论 预充液中加入盐酸戊乙奎醚0.6 mg/kg或2 mg/kg可减轻围CPB期大鼠肠粘膜屏障功能的损伤,且呈剂量依赖性.     

盐酸戊乙奎醚对小鼠胃肠运动及组织胃动素的影响

目的 观察盐酸戊乙奎醚对小鼠胃肠运动及组织胃动素的影响.方法 健康昆明小鼠24只,体重18～22 g,雌雄不拘,随机均分三组.盐酸戊乙奎醚组(P组)腹腔注射盐酸戊乙奎醚0.3 mg/kg,阿托品组(A组)腹腔注射阿托品0.3 mg/kg,对照组(C组)给予等容量生理盐水.各组给药15 min后以营养性半固体糊0.8 ml灌胃,20 min后处死小鼠.采用放免法测定胃动素水平；计算胃残留率和小肠推进率.结果 与A组比较,P、C组小鼠组织的胃动素浓度、小肠推进率升高；胃残留率降低(P＜0.05).结论 盐酸戊乙奎醚不抑制胃肠运动和胃动素的分泌.     

盐酸戊乙奎醚对老年患者非心脏手术后早期认知功能的影响

目的 观察术前应用盐酸戊乙奎醚0.02 mg/kg对老年患者全麻下非心脏手术后早期认知功能的影响.方法 选择全麻下行择期非心脏手术且年龄＞65岁的老年患者60例,随机分为盐酸戊乙奎醚组和对照组.盐酸戊乙奎醚组在麻醉诱导前10 min静脉注射盐酸戊乙奎醚0.02mg/kg;对照组则给等容积生理盐水.麻醉诱导后持续微量泵注射丙泊酚及瑞芬太尼、间断注射阿曲库铵维持麻醉.分别在麻醉前和麻醉后3d采用简易智力量表进行神经心理学评估.结果 因各种原因,仅有41例患者完成全部测试,其中盐酸戊乙奎醚组20例,对照组21例.盐酸戊乙奎醚组术后认知功能障碍( POCD)发生率为35.0％,对照组为38.1％,两组间差异无统计学意义.结论 术前静脉注射0.02 mg/kg盐酸戊乙奎醚对老年患者非心脏手术POCD发生率无显著影响.     

盐酸戊乙奎醚对非停跳冠状动脉搭桥术后患者肺部并发症发生的预防效果

目的 评价术前静脉注射盐酸戊乙奎醚对非停跳冠状动脉搭桥术后患者肺部并发症(PPC)发生的预防效果.方法 非停跳冠状动脉搭桥术患者140例,性别不限,年龄35 ～ 80岁,体重55 ～ 80 kg,ASA分级Ⅱ或Ⅲ级.采用随机数字表法,将其分为2组(n=70):对照组(C组)和盐酸戊乙奎醚组(P组).于气管插管后即刻P组缓慢静脉注射盐酸戊乙奎醚20 μg/kg(5 ml),C组以等容量生理盐水替代.记录术后72 h内患者PPC的发生情况.结果 C组和P组PPC发生率分别为33％和16％.与C组比较,P组PPC发生率降低(P＜0.05).结论 术前静脉注射盐酸戊乙奎醚20 μg/kg可预防非停跳冠状动脉搭桥术患者PPC的发生.     

盐酸戊乙奎醚对新生大鼠内毒素性急性肺损伤时肺氧化应激和细胞凋亡的影响

目的评价盐酸戊乙奎醚对新生大鼠内毒素性急性肺损伤(acute lung injury,ALI)时肺氧化应激和细胞凋亡的影响。方法清洁级健康雄性Wistar大鼠30只,7日龄,体重12~18g。采用随机数字表法分为三组:盐酸戊乙奎醚组(PHC组)、ALI组和生理盐水组(NS组),每组10只。PHC组和ALI组大鼠腹腔注射内毒素5.0mg/kg制备ALI模型。PHC组于内毒素注射前1h腹腔注射盐酸戊乙奎醚2.0mg/kg,NS组和ALI组给予等容量生理盐水。于注射内毒素4h后处死大鼠取肺组织标本,计算肺湿/干重比(W/D),采用硫代巴比妥酸法测定丙二醛(MDA)浓度,黄嘌呤氧化酶法测定大鼠超氧化物歧化酶(SOD)活性,免疫组织化学法测定细胞色素C(Cyt-C)、半胱氨酸天冬蛋白酶-3(Caspase-3)的含量,TUNEL法计数凋亡细胞,计算细胞凋亡指数(AI)。结果与NS组比较,ALI组和PHC组肺W/D和MDA浓度明显升高,SOD活性明显降低(P0.05);与ALI组比较,PHC组肺W/D和MDA浓度明显降低,SOD活性明显升高(P0.05)。与NS组比较,ALI组和PHC组Cyt-C、Caspase-3含量和AI明显升高;与ALI组比较,PHC组Cyt-C、Caspase-3含量和AI明显降低(P0.05)。结论盐酸戊乙奎醚可能通过抑制肺组织氧化应激和细胞凋亡,减轻新生大鼠内毒素性急性肺损伤。     

戊乙奎醚预先给药对大鼠内毒素性脑损伤时NF-κB和iNOS表达的影响

目的 评价戊乙奎醚预先给药对大鼠内毒素性脑损伤时NF-κB和诱导型一氧化氮合酶(iNOS)表达的影响.方法 雄性SD大鼠105只,体重200～220 g,随机分为5组(n=21),D1组、D2组或D3组分别腹腔注射戊乙奎醚0.05、0.15、0.45 mg/kg,NS组和L组给予等容量生理盐水,10min后L组、D1组、D2组和D3组经左颈内动脉注射脂多糖150 μg,NS组给予等容量生理盐水.分别于注射戊乙奎醚后4、6和12 h处死7只大鼠,取脑组织,测定脑组织含水量、NF-κB和iNOS表达水平,光镜和电镜下观察脑组织病理学结果.结果 与NS组相比,L组、D1组、D2组和D3组脑组织含水量、NF-κB和iNOS表达增加(P<0.05);与L组相比,D1组脑组织含水量、NF-κB和iNOS表达差异无统计学意义(P0.05),D2组和D3组脑组织含水量、NF-κB和iNOS表达降低(P<0.05).D2组和D3组脑组织病理学损伤轻于L组.结论 戊乙奎醚0.15、0.45 mg/kg预先给药减轻大鼠内毒素性脑损伤的机制与抑制脑组织NF-κB和iNOS表达上调有关.     

吗啡依赖大鼠脑组织细胞色素P450侧链裂解酶表达水平的变化

目的 评价吗啡依赖大鼠脑组织细胞色素P450侧链裂解酶(P450scc)表达水平的变化.方法 雄性SD大鼠24只,月龄4～8月,体重180～200 g,随机分为3组(n=8):生理盐水对照组(NS组)、吗啡依赖组(MD组)和吗啡戒断组(MW组).MD组和MW组采用剂量递增法腹腔注射吗啡制备大鼠吗啡依赖模型,连续注射7 d,2次/d,剂量分别为5、10、15、20、30、40、50 mg/kg,NS组腹腔注射等容量生理盐水.NS组和MD组于末次给药1 h后断头处死大鼠,MW组于末次给药1 h时注射纳洛酮2 mg/kg,30 min后断头处死取脑,采用Western blot法检测大鼠额叶皮质、海马、纹状体、丘脑P450scc的表达水平.结果 P450scc在额叶皮质、海马、纹状体、丘脑均有表达;与NS组比较,MD组和MW组额叶皮质、纹状体和海马的P450scc表达水平降低(P<0.05).结论 脑组织P450scc表达下调可能与大鼠吗啡依赖的形成有关,而与吗啡戒断无关.     

盐酸戊乙奎醚预先给药对内毒素性急性肺损伤大鼠肺组织NF-κB mRNA表达及SOD活性的影响

目的 探讨盐酸戊乙奎醚预先给药对内毒素性急性肺损伤大鼠肺组织NF-κB mRNA表达及SOD活性的影响.方法 健康雄性SD大鼠32只,月龄2月,体重230～280 g,随机分为4组(n=8),对照组(C组)腹腔和尾静脉均注射生理盐水1 ml/kg;急性肺损伤组(ALI组):腹腔注射生理盐水1 ml/kg,30 min后经尾静脉注射LPS 5 mg/kg;盐酸戊乙奎醚低剂量组(LP组)、高剂量组(HP组)分别腹腔注射盐酸戊乙奎醚0.3和1 mg/kg,30 min后经尾静脉注射LPS 5 mg/kg.静脉注射生理盐水或LPS后6 h时,取肺组织,检测NF-κB mRNA的表达、TNF-α和MDA的含量和SOD活性,计算肺组织湿/干重比(W/D)及含水量,观察肺组织病理学结果.结果 与C组比较,ALI组、LP组和HP组肺组织NF-κB mRNA表达上调,TNF-α及MDA含量升高,SOD活性降低,W/D和肺组织含水量升高(P＜0.05);与ALI组比较,LP组和HP组肺组织NF-κB mRNA表达下调,TNF-α及MDA含量降低,SOD活性升高,W/D和肺组织含水量降低(P＜0.05);与LP组比较,HP组肺组织NF-κB mRNA表达下调,TNF-α及MDA含量降低,SOD活性升高,W/D和肺组织含水量降低(P＜0.05).LP组和HP组肺组织病理学损伤较ALI组减轻.结论 盐酸戊乙奎醚预先给药减轻大鼠内毒素性急性肺损伤的机制可能与下调肺组织NF-κB mRNA表达,降低肺局部炎性反应,增强机体抗氧化能力有关.     

Is the priming principle both effective and safe?

This study determined the priming dose of vecuronium (V), pancuronium (P) and atracurium (A) that resulted in the most rapid onset of neuromuscular blockade (NMB) in 150 patients given either V 0.08 mg/kg, P 0.1 mg/kg or A 0.6 mg/kg. Patients were further divided (n = 10 per group) to receive no prime or 5%, 10%, 15% or 20% of the total dose as a prime followed 5-7 minutes later by the remaining (intubating) dose. A further 10 patients received 0.04 mg/kg d-tubocurarine followed by 1.5 mg/kg succinylcholine (S). Priming significantly shortened the onset of NMB. The priming doses producing the most rapid onset were 0.012 mg/kg for V, 0.015 mg/kg for P and 0.09 mg/kg for A. The S resulted in significantly greater NMB at 60 sec than any priming dose of A, V or P. There was no difference between the three nondepolarizing neuromuscular blockers in shortening the onset of NMB produced by priming. To evaluate both the effect of the "optimal" priming dose in awake patients and the effect of increasing intubating doses on NMB an additional 40 patients were given V 0.012 mg/kg followed by V 0.08, 0.1, 0.12 or 0.15 mg/kg. Increasing the intubating dose did not improve onset of NMB. The "optimal" priming dose, however, resulted in a high incidence of symptoms of muscle weakness. We conclude that priming shortens the onset of NMB similarly between V, P and A but the priming dose producing the most rapid onset of NMB also results in a high incidence of side effects and therefore the priming principle should be used with caution.     

盐酸戊乙奎醚对内毒素性急性肺损伤大鼠肺组织Toll样受体4mRNA和Toll样受体2mRNA表达的影响

目的 探讨盐酸戊乙奎醚对内毒索性急性肺损伤大鼠肺组织Toll样受体4(TLR4)mRNA和Toll样受体2(TLR2)mRNA表达的影响.方法 健康SD大鼠60只,雌雄不拘,体重200～220g,采用随机数字表法,将大鼠随机分为5组(n=12),对照组(C组)、LPS组和低、中、高剂量盐酸戊乙奎醚组(P1组～P3组).C组腹腔注射生理盐水2ml;LPS组腹腔注射LPS 8mg/kg;P1组～P3组分别腹腔注射LPS 8 mg/kg和盐酸戊乙奎醚0.3、1.0和3.0 mg/kg.给药结束后6 h时开胸,心室取血,并取肺组织,采用ELISA法测定血清TNF-α和Ib-6的浓度,RT-PCR法测定肺组织TLR4 mRNA和TLR2 mRNA 的表达水平,并观察肺组织病理学结果.结果 与C组比较,LPS组、P1组～P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均升高(P<0.05);与LPS组比较,P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05),P1组上述指标差异无统计学意义(P>0.05);与P1组比较,P2组和P1组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达均降低(P<0.05);P2组和P3组血清TNF-α、IL-6浓度和肺组织TLR4 mRNA、TLR2 mRNA表达比较差异无统计学意义(P>0.05).P2组和P3组肺组织病理学损伤程度明显轻于LPS组.结论 盐酸戊乙奎醚可通过下调肺组织TLR4 mRNA和耵JR2 mRNA的表达,降低炎性反应,从而减轻大鼠内毒素性急性肺损伤.

Abstract：

Objective To investigate the effect of penehyclidine (PHCD) on Toll-like receptor 4 (TLR4)mRNA and Toll-like receptor 2 (TLR2) mRNA expression in the lung tissue in rats with acute lung injury induced by lipopolysaccharide (LPS) .Methods Sixty healthy SD rats of both sexes weighing 200-220 g were randomly divided into 5 groups ( n = 12 each) :control group (group C) , LPS group and P1-3 groups. Acute lung injury was induced by intraperitoneal (IP) LPS 8 mg/kg in LPS and P1-3 groups. PHCD 0.3, 1.0 and 3.0 mg/kg were given IP after LPS administration in P1-3 groups. The animals were anesthetized at 6 h after IP LPS. Blood samples were collected for determination of serum TNF-α and IL-6 concentrations ( by ELISA) and then sacrificed, the lungs were immediately removed for determination of TLR4 mRNA and TLR2 mRNA expression (by RT-PCR), and microscopic examination. Results LPS significantly increased TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and IL-6 concentrations. PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS-induced increase in TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and ILr6 concentrations.The lung histopathologic damage was significantly ameliorated in P2 and P3 groups as compared with group LPS.Conclusion PHCD can protect the lungs against LPS-induced acute lung injury through inhibiting TLR4 mRNA and TLR2 mRNA expression in the lung tissue and reducing the inflammatory response.     

盐酸戊乙奎醚预先给药对新生大鼠内毒素性急性肺损伤时NF-κB活性的影响

目的 探讨盐酸戊乙奎醚预先给药对新生大鼠内毒索性急性肺损伤时NF-kB活性的影响.方法 健康新生Wistar大鼠30只,雌雄不拘,日龄7 d,体重18～21 g,随机分为3组(n=10):对照组(C组)、急性肺损伤组(ALI组)和盐酸戊乙奎醚预先给药组(P组).采用腹腔注射内毒素3 mg/kg的方法制备急性肺损伤模型,P组腹腔注射盐酸戊乙奎醚0.5 mg/kg,30 min后制备模型,C组腹腔注射等容量生理盐水.于腹腔注射内毒素4 h时处死大鼠取肺,称重后计算肺湿,干重比,电镜下观察肺组织病理学结果,采用免疫组织化学法检测NF-kB p65的表达水平,采用酶联免疫吸附法测定TNF-α、IL-1 β及IL-10的含量.结果 与C组比较,ALI 组和P组肺湿/干重比、TNF-α、IL-1β、IL-10含量及NF-KB p65表达水平升高(P＜0.05);与ALI 组比较,P组肺湿/干重比、TNF-α、IL-1β、IL-10含量及NF-kBp65表达水平降低(P＜0.05).病理学结果显示:P组肺组织损伤程度较ALI组明显减轻.结论 盐酸戊乙奎醚预先给药可通过抑制肺组织NF-kB活化,降低炎性反应,减轻新生大鼠内毒素性急性肺损伤.     

盐酸戊乙奎醚对大鼠胸部撞击致急性肺损伤及肺组织Toll样受体4表达的影响

目的 探讨盐酸戊乙奎醚对大鼠胸部撞击致急性肺损伤及肺组织Toll样受体4(TLR4)表达的影响.方法 健康雄性SD大鼠96只,体重250～300 g,采用随机数字表法,将大鼠随机分为3组(n=32):对照组(C组)只麻醉,不制备模型;肺损伤组(ALI组);盐酸戊乙奎醚组(PHcD组)模型制备后即刻,腹腔注射盐酸戊乙奎醚2 mg/kg.砝码(300g)于95 cm高处自由落体撞击大鼠心前区以制备急性肺损伤模型.于模型制备后2、8、12和24h时取8只大鼠,取动脉血样,测定血清TNF-α浓度.于模型制备后8 h取8只大鼠,取动脉血样,行动脉血气分析,随后处死大鼠,取肺组织观察病理学结果,测定干/湿重比(W/D比)、髓过氧化物酶(MPO)活性和TLR4表达水平.结果 与c组比较,ALI组和PHCD组pH值和PaO2下降,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度升高(P＜0.01);与ALI组比较,PHcD组pH值和PaO2升高,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度降低(P＜0.05).PHcD组肺组织病理性损伤较ALI组减轻.结论 盐酸戊乙奎醚可减轻大鼠胸部撞击诱发的急性肺损伤,其机制与下调肺组织TLR4表达,降低炎性反应有关.

Abstract：

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) on acute lung injury (ALI) induced by blunt chest trauma and Toll-like receptor 4 (TLR4) expression in the lung tissues in rats.Methods Ninety-six male SD rats weighing 250-300 g were randomly divided into 3 groups ( n = 32 each):control group (group C), ALI group and PHCD group. ALI was induced by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs in anesthetized rats according to the method described by Raghavendran et al. PHCD 2 mg/kg was injected intraperitoneally immediately after ALI was induced in group PHCD. Eight rats were selected at 2, 8, 12 and 24 h after ALI was induced, and arterial blood samples were collected for determination of the serum TNF-α concentration. Eight rats were selected at 8 h after ALI was induced, arterial blood samples collected for blood gas analysis and then the rats sacrificed. The lungs were immediately removed for determination of W/D lung weight ratio, myeloperoxidase (MPO) activity and TLR4 expression, and microscopic examination. Results The pH value and PaO2 were significantly lower, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration higher in groups ALI and PHCD than in group C (P ＜ 0.01 ). The pH value and PaO2 were significantly higher, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration lower in group PHCD than in group ALI ( P ＜ 0.05). The lung histopathologic damage was significantly ameliorated in PHCD group as compared with ALI group. Conclusion PHCD can protect the lungs against blunt chest trauma-induced ALI, and the down-regulation of TLR4 expression in lung tissues and reduction of inflammatory response are involved in the mechanism.     

小剂量氯胺酮对抑郁大鼠异丙酚麻醉下电休克疗效的影响

目的 评价小剂量氯胺酮对抑郁大鼠异丙酚麻醉下电休克疗效的影响.方法 成年雄性SD大鼠60只,体重200～250 g,采用慢性不可预见轻度应激建立抑郁模型.采用随机数字表法,将大鼠随机分为6组(n=10):对照组(C组)、抑郁组(D组)、异丙酚组(P组)、异丙酚+电休克治疗组(PE组)、氯胺酮+异丙酚组(KP组)和氯胺酮+异丙酚+电休克治疗组(KPE组).C组不作任何处理;P组和PE组腹腔注射异丙酚100mg/kg,KP组和KPE组腹腔注射氯胺酮10 mg/kg和异丙酚80mg/kg,待翻正反射消失后,将电极夹在双侧鼠耳,P组和KP组不通电,PE组和KPE组通电治疗,1次/d,连续7 d.分别于建模前、建模后和治疗结束后,行糖水消耗(SFC)实验,计算SFC百分比;行Morris水迷宫实验,测试学习记忆功能.结果 与C组比较,建模后D组、P组、FE组、KP组及KPE组SFC百分比降低,逃避潜伏期延长,目标象限停留时间缩短(P＜0.05),治疗后KPE组SFC百分比、逃避潜伏期及目标象限停留时间差异无统计学意义(P＞0.05).与D组比较,治疗后KPE组SFC百分比升高(P＜0.05),逃避潜伏期及目标象限停留时间差异无统计学意义(P＞0.05),FE组SFC百分比升高,逃避潜伏期延长,目标象限停留时间缩短(P＜0.05).与PE组比较,治疗后KPE组SFC百分比升高,逃避潜伏期缩短,目标象限停留时间延长(P＜0.05).结论 小剂量氯胺酮不仅可增强异丙酚麻醉下电休克治疗抑郁大鼠的效果,还可进一步减轻电休克所致认知功能损害.

Abstract：

Objective To evaluate the effect of low-dose ketamine on the efficacy of electroconvulsive therapy (ECT) under propofol anesthesia in depressed rats. Methods Sixty adult male SD rats weighing 200-250 g were used in this study. The depression model was established by chronic unpredictable mild stress (CUMS). The animals were then randomly divided into 6 groups (n = 10 each): control group (group C), depression group (group D), propofol group ( group P), propofol + ECT group ( group PE), ketamine + propofol group ( group KP), and ketamine + propofol + ECT group (group KPE). Groups P and KP received intraperitoneal propofol 100 mg/kg and ketamine 10 mg/kg + propofol 80 mg/kg respectively, and groups PE and KPE received ECT after intraperitoneal injection of propofol 100 mg/kg and ketamine 10 mg/kg + propofol 80 mg/kg respectively once a day for 7 consecutive days. All rats underwent sucrose fluid consumption and Morris water maze tests before CUMS, after CUMS, and after treatment. Results Compared with group C, the sucrose consumption percentage was significantly decreased, the escape latency was prolonged, and the time spent in the target quadrant (the original platform quadrant) was shortened after CUMS in D, P, PE, KP and KE groups ( P ＜ 0.05). Compared with group D,the sucrose consumption percentage was significantly increased (P ＜ 0.05), while no significant change in the escape latency and time spent in the target quadrant was found after treatment in group KPE ( P ＞ 0.05 ), and the sucrose consumption percentage was significantly increased, the escape latency was prolonged, and the time spent in the target quadrant was shortened after treatment in group PE ( P ＜ 0.05). Compared with group PE, the sucrose consumption percentage was significantly increased, the escape latency was shortened, and the time spent in the target quadrant was prolonged after treatment in group KPE ( P ＜ 0.05). Conclusion Low-dose ketamine can not only enhance the efficacy of ECT under propofol anesthesia in depressed rats, but also reduce cognitive impairment induced by ECT.