清开灵对急性有机磷中毒大鼠脑自由基代谢及血清NSE mRNA表达的影响

目的：观察清开灵对急性有机磷中毒（AOPP）大鼠脑损伤的影响。方法成年雄性SD大鼠32只,随机分为正常对照组、中毒组、常规治疗组和清开灵治疗组,每组8只。正常对照组给予同等容量的生理盐水灌胃,其余3组用氧化乐果灌胃80mg/kg。造模成功后常规治疗组立即予长托宁0.1mg/kg、氯解磷定30mg/kg肌肉注射,清开灵治疗组在常规治疗同时给予清开灵1.5ml/kg腹腔注射。各组在造模完成后6h处死大鼠,下腔静脉取血,离心分离血清,采用荧光定量PCR检测神经元特异性烯醇化酶（NSE）mRNA的表达;断头取大脑组织匀浆,测MDA含量和SOD活性。结果与中毒组比较,常规治疗组和清开灵治疗组血清NSE mRNA水平和脑组织MDA含量下降（P〈0.05）,而脑组织SOD活性升高（P〈0.05）。与常规治疗组比较,清开灵治疗组效果更好（P〈0.05）。结论辅以清开灵治疗可以更有效地减轻急性有机磷中毒大鼠脑的氧化应激反应,更好地发挥脑保护作用,从而减少血清中NSE mRNA表达。     

丹参多酚酸盐对缺血再灌注损伤大鼠心肌的保护作用及机制

目的探讨丹参多酚酸盐对缺血再灌注损伤大鼠心肌的影响及可能机制。方法 45只SD大鼠随机分为模型组、丹参组和对照组各15只。模型组和丹参组大鼠采用线栓法制备心肌缺血再灌注损伤模型,对照组仅插入线栓不结扎冠状动脉。造模成功后丹参组和对照组腹腔注射21mg/(kg·d)丹参多酚酸盐溶液连续10d,模型组腹腔注射等量生理盐水。比较腹腔注射丹参多酚酸盐溶液0.5、1、3、8h后3组心电图Ⅱ导联ST段改变;腹腔注射10d处死大鼠后取出心脏,行HE染色观察心肌组织病理形态变化,采用ELISA法测定血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、心肌肌钙蛋白T(cardiac troponin T,cTnT)水平,Western blot法检测心肌组织B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2assaciated X protein,Bax)、Ras同源蛋白A(Ras homologous A,RhoA)蛋白水平。结果腹腔注射0.5、1、3、8h模型组和丹参组心电图Ⅱ导联ST段电压逐渐降低;模型组、丹参组各时间点ST段电压均高于对照组,且模型组高于丹参组(P0.05);腹腔注射10d,对照组心肌细胞形态和结构完整,未见炎症细胞浸润;模型组心肌细胞排列紊乱、细胞肿胀,有大量炎症细胞浸润;丹参组心肌细胞排列紊乱、肿胀,可见局灶性坏死心肌细胞,炎症细胞浸润程度较模型组轻;腹腔注射10d,模型组、丹参组血清IL-6[(372.0±36.2)、(183.0±40.0)ng/L]、cTnT[(273.0±18.6)、(160.0±23.2)ng/L]、TNF-α[(4 600.0±350.0)、(3 800.0±234.0)ng/L]水平均高于对照组[(80.0±18.3)、(82.0±20.1)、(800.0±80.5)]ng/L](P0.05),且模型组高于丹参组(P0.05);腹腔注射10d,模型组、丹参组大鼠心肌组织RhoA(2.85±0.21、1.75±0.27)、Bcl-2(1.98±0.28、5.50±0.48)及Bax蛋白水平(6.03±0.54、13.59±0.38)均高于对照组(0.20±0.01、0.04±0.02、0.04±0.01)(P0.05),且模型组心肌组织RhoA、Bax蛋白水平高于丹参组,Bcl-2蛋白水平低于丹参组(P0.05)。结论丹参多酚酸盐可改善SD大鼠心肌缺血再灌注损伤,其机制可能与抑制炎症反应及RhoA表达,调控凋亡蛋白及抗凋亡蛋白平衡有关。     

盐酸戊乙奎醚对大鼠双下肢缺血再灌注后心肌氧化应激反应的影响

【目的】观察盐酸戊乙奎醚对大鼠双下肢缺血再灌注后心肌氧化应激反应的影响。【方法】60只Sprague-Dawley大鼠随机分成3组：①对照组（C组）：②缺血再灌注组（I／R组）：③盐酸戊乙奎醚＋I／R组（M组）。观察心组织病理变化,比色测定心肌组织超氧化物歧化酶（SOD）含量、丙二醛（MDA）,心肌和血清髓过氧化物酶（MPO）,夹心法酶联免疫吸附（ELISA法）测定心肌和血清肿瘤坏死因子-α（TNF—α）、白细胞介素-10（IL-10）含量,统计各组24小时生存率。【结果】I／R组：与其他两组比较心肌组织匀浆MDA、心肌和血清MPO、TNF-α含量明显升高,心肌病变最为严重;与C组比较：心肌和血清IL-10含量显著增高;心肌SOD含量、生存率显著下降。M组病变较对I／R组明显改善,生存率明显提高,心肌组织匀浆MDA、心肌和血清MPO、TNF—α含量显著下降;心肌SOD活性、心肌和血清IL-IO含量显著增高。【结论】盐酸戊乙奎醚可明显减轻肢体缺血再灌注所引起心肌氧化应激反应、保护心肌,其机制可能是通过减轻全身炎症反应,从而减少心肌中性粒细胞聚集,从而缓解心肌细胞氧化应激反应。     

血必净对急性百草枯中毒大鼠MDASOD和GSH—Px的影响

目的通过血必净（XBJ）对急性百草枯（PQ）中毒大鼠丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH—Px）影响的实验研究,观察血必净对急性百草枯中毒大鼠是否具有抗氧化治疗的作用。方法54只SD大鼠随机分为对照组、中毒组和XBJ组,中毒组和XBJ组按120mg／kg百草枯灌胃,2h后XBJ组腹腔注射血必净10ml／kg,对照组和中毒组腹腔注射等体积生理盐水,1次／d。于给药后6h、24h、72h取大鼠眼眶血,比色法检测血清中MDA的含量及SOD、GSH—Px的活力。结果给药后6h、24h、72h中毒组血清MDA含量高于其他组,以24h升高最明显,同时SOD、GSH—Px水平明显下降;XBJ组较中毒组MDA明显降低,而SOD、GSH—Px明显升高（P〈0．05）。结论血必净（XBJ）可以明显降低急性百草枯中毒大鼠MDA的生成,并增加SOD、GSH—Px的活力,可使急性百草枯中毒大鼠引起的脂质过氧化损害得到改善,对急性百草枯中毒大鼠具有抗氧化治疗的作用。     

丹参多酚酸盐对胸腔镜术中单肺通气 相关肺损伤的保护作用*

目的观察丹参多酚酸盐对胸腔镜术中单肺通气相关肺损伤的保护并探讨其相关机制。方法将44例接受胸腔镜手术治疗的单肺通气(OLV)患者平均随机分为对照组与治疗组,治疗组在OLV前进行丹参多酚酸盐静脉滴注预处理。分别在OLV开始时、OLV开始后1 h及OLV开始后2 h观察并比较两组患者血清中白介素-6(IL-6)、超氧化物歧化酶(SOD)、丙二醛(MDA)、全血中性粒细胞比例(PMN%)以及OLV前后肺组织中表面活性蛋白A(SPA)的水平。结果与OLV开始时相比,所有患者在OLV后血清中IL-6及MDA水平显著升高,血清中SOD水平及肺组织中SPA水平显著降低,差异均有显著性(P<0.05);在OLV后,与对照组相比,治疗组血清IL-6及MDA显著降低,血清SOD及肺组织SPA水平则显著升高(P<0.05)。结论丹参多酚酸盐预处理可对胸腔镜手术中OLV相关肺损伤起保护作用。     

急性CO中毒患者血清SOD、GSH-Px活性及MDA水平的变化及其意义

目的：探讨急性一氧化碳中毒（ACOP）患者血清丙二醛（MDA）水平、谷胱甘肽过氧化物酶（GSH－Px）及超氧化物歧化酶（SOD）活性的变化，了解ACOP时自由基氧化损伤在其病理机制中的作用。方法：选择不同中毒程度的ACOP患者70例，分别于入院即刻、12、24、48、72h抽血测定血清中MDA水平及SOD、GSH－Px的活性。结果：ACOP时，中度CO中毒组与轻度中毒组比较，血清MDA水平升高，但不具有显著性意义（P＞0．05）；重度中毒组与中度中毒组比较，MDA水平显著性升高（P＜0．05），且24,48h仍维持在较高水平。中度中毒组与轻度中毒组比较，血清SOD及GSH－Px在性水平降低，但不具有显著性意义（P＞0．05）；重度中毒组与中度中毒组比较，SOD及GSH－Px活性水平显著降低（P＜0．05）。结论：ACOP时血清MDA水平升高，SOD及GSH－Px活性降低，提示ACOP时存在着严重自由基氧化损伤的病理过程，为ACOP治疗过程中抗氧化治疗提供了依据，SOD及GSH－Px活性降低，提示ACOP时存在着严重自由基氧化损伤的病理过程，为ACOP治疗过程中抗氧化治疗提供了依据。同时，血清MDA水平和SOD及GSH－Px活性也可作为中毒损伤程度评估，预后判定的指标之一。     

乌司他丁对百草枯中毒大鼠肾脏损伤的保护作用及机制研究

目的 观察百草枯(PQ)中毒大鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)含量及肾脏细胞凋亡的变化,探讨乌司他丁(UTI)对PQ中毒相关肾损伤的保护作用及相关机制.方法 将72只SD大鼠随机分为对照组、PQ组和UTI组,每组24只.PQ组以生理盐水稀释PQ 80 mg/kg一次性灌胃;UTI组PQ灌胃后以UTI 100 000 U/kg腹腔注射,每日一次;对照组生理盐水一次性灌胃.于不同处理后24、48、72 h分别观察肾组织病理学变化、测定血清中SOD活性、MDA含量,TUNEL法测定肾脏凋亡细胞率.结果 PQ组各时间点血清MDA含量较对照组各相应时间点显著升高(P<0.01),SOD活性较对照组各相应时间点显著降低(P<0.01).与PQ组比较,UTI组各时间点肾组织MDA含量显著降低(P<0.01),SOD活性显著升高(P<0.01).PQ组各时间点凋亡细胞率较对照组各相应时间点升高(P<0.01);UTI组各时间点凋亡细胞率较PQ组显著降低(P<0.01).肾脏细胞凋亡率与SOD活性呈负相关(r=-0.805,P<0.01),与MDA含量呈正相关(r=0.623,P<0.05).结论 UTI对PQ中毒后肾脏损伤有保护作用,其机制可能是通过抗脂质过氧化,减轻肾脏细胞凋亡来实现的.     

兔肢体缺血-再灌流对心肌细胞凋亡及心功能的影响

目的观察肢体缺血-再灌流时心功能的变化和心肌细胞凋亡状况。方法健康家兔30只,随机均分为假手术对照组(SC)、单纯缺血组(Ⅰ)和缺血再灌流组(JR)。免疫组化法检测心肌组织Bcl-2和Bax蛋白表达；原位缺口末端标记法(TUNEL)检测心肌细胞凋亡；比色法测定心肌组织超氧化物岐化酶(SOD)和髓过氧化物酶(MPO)活性-丙二醛(MDA)含量,测定血清乳酸脱氢酶(LDH)活性；通过生理记录仪观察心功能指标；光镜下观察心肌病变。结果IR组心肌组织细胞凋亡指数明显高于其它两组,Bax蛋白表达明显增多,同时IR组心肌组织SOD活性降低,MDA含量增高,血清LDH活性增高,左心室功能下降,且MDA含量与LDH活性、Bax蛋白表达和凋亡指数之间呈显著正相关,光镜下可见心肌病变。结论肢体缺血-再灌流可造成心肌损伤,心功能下降,与氧化损伤和细胞凋亡有关。     

褪黑素对癫痫大鼠海马氧化应激及神经元凋亡的影响

目的探讨褪黑素对癫痫大鼠海马氧化应激及神经元凋亡的影响及其机制。方法成年雄性Sprague-Dawley大鼠72只等分为对照组、模型组、褪黑素低剂量组和褪黑素高剂量组。模型组侧脑室注射马桑内酯50μg/kg,褪黑素低、高剂量组分别于腹腔注射褪黑素20 mg/kg和60 mg/kg后30 min,侧脑室注射马桑内酯50μg/kg。癫痫持续60 min后,采用紫外分光光度计检测丙二醛(MDA)、超氧化物歧化酶(SOD)的含量;原位末端标记法(TUNEL法)检测大鼠海马CA3区神经元凋亡;电镜观察海马CA3区神经元及其线粒体改变。结果与对照组相比,模型组海马神经元、线粒体出现明显超微结构损伤,凋亡细胞数显著增多(P0.001),海马SOD显著降低(P0.001),MDA显著升高(P0.001)。与模型组相比,褪黑素低剂量组大鼠海马神经元、线粒体超微结构损伤有所改善,凋亡细胞数明显减少(P0.01),SOD升高(P0.05),MDA降低(P0.05);褪黑素高剂量组大鼠海马神经元、线粒体超微结构损伤明显改善,凋亡细胞数显著减少(P0.001),且与对照组相比无显著性差异(P0.05),SOD显著升高(P0.001),MDA显著降低(P0.001)。结论给予外源性褪黑素可明显减少癫痫大鼠海马神经元凋亡,高剂量效果更佳,其作用机制可能涉及褪黑素对抗氧化应激反应,减轻神经元、线粒体损伤。     

盐酸戊乙奎醚对氧化乐果中毒大鼠的治疗作用

目的：研究盐酸戊乙奎醚（PCHE）对氧化乐果中毒大鼠的治疗作用及其诱发的循环抑制的影响。方法：将实验大鼠随机分为盐水对照组（SC组）、中毒对照组（OC组）、阿托品治疗组（OA组）和长托宁治疗组（OP组）,观察麻醉大鼠有机磷农药中毒症状,心率（HR）和血压（MBP）的变化,并检测肌酸激酶（CK）、乳酸脱氢酶（LDH）和胆碱酯酶（CHE）活力。结果：OC组出现分泌物增多、肌颤、呼吸困难,而OA组和OP组分泌物少,其中OP组大鼠的肌颤、呼吸困难程度较OA组轻,血流动力学稳定,CHE活力恢复快。结论：PCHE是一种理想的治疗有机磷农药中毒的解毒剂。     

盐酸戊乙奎醚对氧化乐果中毒大鼠心肌的作用

目的研究盐酸戊乙奎醚(penehyclidine hydrochloride,PCHE)对氧化乐果中毒大鼠的治疗效果及其对心脏病理改变的影响。方法将实验大鼠随机分为盐水对照组(SC组)、中毒对照组(OC组)、阿托品治疗组(OA组)和长托宁治疗组(OP组),观察实验大鼠有机磷农药中毒的治疗效果和心肌的病理改变。结果OC组大鼠迅速出现有机磷农药中毒症状并死亡,而OA组和OP组大鼠症状较轻,但OP组大鼠的肌颤、肌无力程度较OA组轻,且心肌的病理损害小。结论PCHE对有机磷农药中毒所引起的心肌损害有保护作用。     

高压氧对大鼠海马神经元Bcl-2蛋白表达的影响

背景高压氧是治疗急性一氧化碳中毒的首选方法.但是,高压氧治疗急性一氧化碳中毒的机制,尤其是治疗一氧化碳中毒迟发性脑病的机制,目前还不清楚.目的观察急性一氧化碳中毒大鼠海马区神经元病理改变,研究高压氧治疗对一氧化碳中毒大鼠海马区神经元Bcl-2蛋白表达的影响.设计以实验动物为研究对象,完全随机设计,对照实验研究.单位一所军医大学医院的急诊科、一所市级医院的检验科和一所军医大学的高压氧治疗中心.材料实验在解放军第四军医大学航空航天医学系高压氧治疗中心实验室进行,选择60只雄性SD大鼠.干预60只大鼠随机分成3个组(正常对照组、一氧化碳中毒组、一氧化碳中毒高压氧治疗组),每组20只,各组大鼠分别暴露在空气或一氧化碳气体(体积分数为3.2×10-3)中60 min,对一氧化碳中毒高压氧治疗组大鼠行高压氧治疗.制备大鼠海马区脑组织病理切片行常规苏木精-伊红染色和Bcl-2染色,观察一氧化碳中毒后第1,,5和7天大鼠海马区神经元损伤和Bcl-2蛋白表达变化的特点.主要观察指标病理形态学改变和Bcl-2蛋白表达变化.结果一氧化碳中毒组大鼠海马可见大量变性坏死神经元,高压氧治疗组海马区神经元变性坏死减少,cl-2蛋白表达增多,尤以染毒后3和5 d明显(P＜0.05).结论高压氧治疗可以促进急性一氧化碳中毒大鼠海马区神经元Bcl-2蛋白表达,具有保护神经元的作用.     

聚维酮碘腹腔灌洗对腹腔海水浸泡伤大鼠术后败血症的防治作用

目的　观察聚维酮碘腹腔灌洗对防治腹腔海水浸泡伤后败血症的作用。方法　建立大鼠腹腔开放伤动物模型。选取 SD大鼠 84只 ,随机均分为腹腔海水浸泡组 (A组 ,4 2只 )及聚维酮碘灌洗组 (B组 ,4 2只 ) ,观察每个时间点 6只动物处理前后血浆内毒素 (ET)和肿瘤坏死因子 (TNF)的变化及每组 18只大鼠腹腔灌洗后 2 4 h血细菌培养阳性率。结果　 1腹腔海水浸泡后 A、B组 ET及 TNF水平均显著升高 (与浸泡前比较 ,P均 <0 .0 5 ) ;自术后 12 h开始 ,B组血浆 ET及 TNF水平均显著低于 A组 (P<0 .0 5或 P<0 .0 1)。2术后 2 4 h,B组细菌培养总阳性率为 16 .7% (3/ 18) ,显著低于 A组 77.8% (14 / 18,P<0 .0 1)。结论　聚维酮碘灌洗腹腔可显著降低血浆 ET及 TNF水平 ,降低血细菌培养阳性率 ,减少机体败血症发生的可能性。     

富硒治疗对大鼠急性一氧化碳中毒性脑病的作用

目的:研究富硒治疗对急性一氧化碳(CO)中毒性脑病模型大鼠的作用及其作用机制。方法:60只SD大鼠随机分为正常对照组(BC组)、急性CO中毒组(CO组)、低硒治疗组(L-Se组)、中硒治疗组(M-Se组)、高硒治疗组(H-Se组)各12只。腹腔注射CO制备急性CO中毒模型。造模前30 d及造模后每天分别给予各组纯水或不同剂量富硒药物灌胃治疗。造模后第7天、第14天分别取脑及外周脏器,HE染色观察组织变化;对脑皮质行小白蛋白(PV)免疫组化染色,Western Blotting检测皮质PV和Caspase-3的蛋白表达水平。结果:硒对急性CO中毒大鼠模型的肝脏、肾脏无明显的毒性损伤。H-Se组在造模后第7天、第14天的皮质PV阳性细胞数均高于CO组(P<0.05);L-Se组、M-Se组在造模后第7天、第14天的皮质PV阳性细胞数与CO组无明显差异(P>0.05);H-Se组的PV阳性细胞数与BC组无明显差异(P>0.05)。H-Se组在造模后第7天、第14天的PV表达量高于CO组(P<0.05),Caspase-3蛋白表达低于CO组(P<0.05),与BC组无明显差异(P>0.05);L-Se组、M-Se组在造模后第7天、第14天的PV和Caspase-3蛋白表达量与CO组无明显差异(P>0.05)。结论:高剂量的硒治疗可明显上调PV,减少Caspase-3的活化。     

By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alterations induced by hypertonic peritoneal dialysis solution.

OBJECTIVE: Chronic peritoneal dialysis (PD) may eventually result in vascular alterations of varying degree, which lead to progressive reduction in dialytic efficacy. Although the pathogenesis has not been elucidated yet, vascular endothelial growth factor (VEGF) has been proposed to play a central role in the process leading to vascular alterations. DESIGN: Rats were allocated to three groups: no treatment, intraperitoneal introduction of hypertonic PD solution alone, and intraperitoneal introduction of hypertonic PD solution plus octreotide. After 4 weeks, a 1-hour peritoneal equilibration test (PET) was performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration volume (UF), and levels of dialysate protein and VEGF were determined. Peritoneal membrane histology was evaluated by light microscopy. RESULTS: Compared with the control group, rats treated with hypertonic PD solution showed dramatically deranged peritoneal function tests (UF: 5.8 +/- 0.9 mL vs 1.3 +/- 0.6 mL; D/P urea: 0.49 +/- 0.1 vs 0.74 +/- 0.04; D1/D0 glucose: 0.55 +/- 0.05 vs 0.34 +/- 0.06) and morphology (thickness: 4.6 +/- 0.4 mu vs 62 +/- 12 mu; neovascularisation: 0.1 +/- 0.3 vessels per field vs 2.2 +/- 0.3 vessels per field). Similarly, a higher level of VEGF was found in the rats treated with hypertonic PD solution. In rats treated with hypertonic solution plus octreotide, peritoneal thickness was not completely reduced (25 +/- 5 mu), but peritoneal functions were protected (UF: 4.0 +/- 0.5 mL; D/P urea: 0.58 +/- 0.02; D1/D0 glucose: 0.51 +/- 0.02). Moreover, VEGF level and neoangiogenesis were significantly less in the octreotide group than in the group treated with hypertonic dextrose alone. CONCLUSION: Our data document that, by increasing the production of VEGF, a high glucose concentration can cause vascular alterations within the peritoneal membrane. Octreotide can protect against the vascular alterations and preserve peritoneal function by inhibiting overexpression of VEGF and regulating the inflammatory response in the peritoneum.     

Effects of acute organophosphate poisoning on thyroid hormones in rats

The aim of this study was to investigate the effects of organophosphate poisoning on thyroid hormones. In this study, male Wistar albino rats weighing 200-225 g were used. The rats were divided into 4 groups. Group 1 (n = 10) was administered 30 mg/kg lethal dose of methamidophos, whereas group 2 (n = 7) was treated with physiologic NaCl (SP). Group 3 (n = 10) was treated with 30 mg/kg of methamidophos. When cholinergic symptoms developed among the rats in group 3, they were treated with 40 mg/kg pralidoxime intraperitoneally (IP) and administered atropine IP until the cholinergic symptoms disappeared. Group 4 (n = 7) was treated with SP. After the cholinergic symptoms appeared among the rats in group 1, intracardiac blood samples were taken. In group 3, blood samples were taken after the cholinergic symptoms had disappeared. Then triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), and plasma choline esterase (PCE) levels were studied by RIA. The Kruskal-Wallis test and Mann-Whitney U test were used for comparison between groups. Bonferroni correction was applied when multiple comparisons were made. T3, T4, and TSH levels decreased in group 1 compared with group 2 (P < 0.01). When the results between groups 3 and 4 were compared, it was found that the T3 and T4 levels in group 3 decreased while the decreases in T3 levels were statistically significant (P < 0.01). When comparing the results of groups 1 and 3, the T4 level was lower in group 1 and the T3 level was higher in group 3 (P < 0.01). The TSH level increased in group 3 after treatment (P < 0.01). Thyroid hormones were affected after acute organophosphate poisoning. Hypothyroidism and sick euthyroid syndrome was observed during poisoning and after treatment. In serious poisoning, there may be a poor prognosis, but more extensive studies will illuminate the issue in depth.     

腹膜透析对氧化乐果中毒兔肝脏及血清胆碱酯酶的影响

目的 探讨腹膜透析(PD)对急性有机磷农药中毒(AOPP)致肝损伤的保护作用及对血清胆碱酯酶的影响.方法 建立兔的氧化乐果中毒模型,动态观察对照组、PD组肝脏功能、白蛋白、血清胆碱酯酶水平及光镜下肝脏病理改变.结果 染毒后两组动物血清胆碱酯酶明显降低,肝脏功能改变明显,但PD组血清且日碱酯酶恢复较快,肝功能指标改变明显轻于对照组,PD组白蛋白水平低于对照组;光镜下两组均有肝细胞受损并出现中毒性肝炎征象,PD组肝细胞损害明显轻于对照组.结论 PD对AOPP致肝脏损害具有积极的保护作用,并有利于血清胆碱酯酶的恢复.     

百草枯致肺纤维化病变区域分布的影像学研究

目的 利用MicroCT系统对百草枯(paraquat,PQ)所致肺纤维化大鼠的影像学表现和CT值变化,分析病变区域在肺脏中的主要分布部位.方法 15只Sprague Dawley大鼠随机(随机数字法)分为对照组和百草枯染毒组.染毒组以4 mg/mL质量浓度的百草枯稀释溶液按14 mg/kg一次性腹腔注射,对照组代以等剂量生理盐水注射.分别于染毒后第3,7,14,28天利用MicroCT行大鼠活体肺组织扫描,根据扫描图像所获得资料,采用单因素方差分析(t检验)和组间比较等统计学方法,分析比较各纤维化征象的显示率差异,以及在所给测定区域(称感兴趣区ROI)的平均CT值变化情况.结果 大鼠百草枯染毒后出现不同程度的肺纤维化征像,且大部分征像出现时间优势地分布于染毒1周后,病变区域优势地分布于肺脏的中下部偏外区域;ROI的CT值变化结果表明,随着染毒时间的延长肺的密度逐渐增加,且统计分析可见肺纤维化的发生发展在左右肺上差异无统计学意义(P>0.05),但在肺脏不同的部位间纤维化程度存在的差异具有统计学意义(P<0.05或P<0.01).结论 肺纤维化时各征像出现的时间不同,优势地分布于1周后;肺组织的密度随肺纤维化发展时间的延长逐渐增加,且其病变区域主要集中于肺脏的中下叶偏外围部分.

Abstract：

Objective To analyze the distribution of main lesion areas in pulmonary fibrosis induced by paraquat in rats by means of radiographic imaages and varied CT value by using MicroCT. Methods A total of 15 male Sprague Dawley rats were randomly (random number) divided into control group and paraquat poisoned group. group. The rats in exposure group were treated with dilute solution of paraquat (4mg/ mL) in dose of 14mg/kg injected intraperitoneally, and the rats in control group were treated with the same volume of saline instead. The lung tissues of all rats were scanned in vivo by using MicroCT on the 3rd, 7th , 14th and 28th days after paraquat or saline administration, respectively. The data from scanned images, rates of observable signs of pulmonary fibrosis and average CT value variation in given regions (region of interest, ROI) were compared between groups and different durations after poisoning by using statistical methods as one factor analysis of variance (t-test). Results Compared with the control group, the rats with acute paraquat poisoning appeared varying degrees of the signs of pulmonary fibrosis. Most of the lesion areas predominantly spread over the lateral regions of the lower lobe of lung, and appeared mainly one week after paraquat poisoning. The opacity of lung shadow seen on the radiograph was significantly increased with time extended after exposure to PQ as a consequence of CT value variation in ROI, and there was no difference in the development of pulmonary fibrosis between right lung and left lung ( P > 0. 05), but there were differences in the extent of fibrosis at different areas in lung (P <0.05 or P < 0.01). Conclusions The signs of pulmonary fibrosis predominantly appeared one week after poisoning. The opacity of lung shadow was increasing gradually during the course of pulmonary fibrosis developed in rats in paraquat poisoning group, and lesion areas predominantly spread over the lateral regions of the lower lube of lung.     

The effect of advanced glycation end-products and aminoguanidine on TNFalpha production by rat peritoneal macrophages.

OBJECTIVE: To evaluate the effect of advanced glycation end-products (AGEs) and the inhibitor of their formation, aminoguanidine, on tumor necrosis factor-alpha (TNFalpha) production (as a functional marker) by rat peritoneal macrophages (PMphi). DESIGN: Charles River rats underwent a daily intraperitoneal injection of peritoneal dialysis solution [(PDS), 4.25 g/dL dextrose; Dialine, Travenol, Ashdod, Israel] for a 2-month period (group E). Another group of rats was subjected to the same protocol with the addition of 25 mg/kg aminoguanidine (group A). Three control groups were utilized: (1) rats that were injected daily with aminoguanidine only (group AO), (2) rats that were injected with Dulbecco's phosphate-buffered saline (group D), and (3) rats in which no intervention was carried out (group C). After 2 months, PMphi were isolated from rat peritoneal effluent and their TNFalpha production measured by ELISA in cell-free culture supernatants, in both the basal state and after 24-hour stimulation with lipopolysaccharide (LPS). The concentrations of AGEs in peritoneal effluent were assayed and correlated to TNFalpha levels. PMphi obtained from normal rats were then incubated for 24 hours with (1) the peritoneal effluent of each of the above respective groups, with or without LPS; (2) increasing concentrations of AGEs (0-250 microg/mL); and (3) increasing concentrations of aminoguanidine (0-7.5 mg/mL), and TNFalpha secretion again determined. RESULTS: After 2 months of daily intraperitoneal injection of PDS, in the basal state, TNFalpha production was significantly higher in PMphi isolated from the peritoneal effluent groups (groups E, A, and AO) compared to controls (group C). Following LPS stimulation, a further increase in TNFalpha secretion was seen, with a significantly greater response in group AO versus groups E, A, and D. Effluent AGEs were markedly elevated only in group E. No correlation was found between TNFalpha secretion by these PMphi and the concentration of AGEs. On incubation with the respective peritoneal effluents (groups E, A, and AO), in both the basal and stimulated state, TNFalpha production by PMphi from normal rats was significantly enhanced compared to group C. Incubation with increasing concentrations of AGEs or aminoguanidine resulted in an increase of TNFalpha secretion by these PMphi. CONCLUSIONS: Following intermittent intraperitoneal administration of glucose-based PDS, rat PMphi are chronically activated, as evidenced by increased basal TNFalpha secretion. The peritoneal effluent of such treated animals is capable of stimulating TNFalpha production by normal rat PMphi. These data suggest that glucose-based PDS acts as a primer of PMphi, which retain their ability to further stimulation by LPS. Although, in vitro, AGEs promote TNFalpha secretion by normal rat PMphi, in vivo, their influence is probably modulated by other factors. Aminoguanidine has a specific inducing effect on rat PMphi, independent of glucose-based PDS.