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二硫代氨基吡咯烷预先给药对内毒素诱发大鼠心肌损伤的影响

Protective effect of pyrrolidine dithiocarbamate pretreatment on myocardium against LPS-induced injury in rats
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摘要 目的评价二硫代氨基吡咯烷预先给药对LPS诱发大鼠心肌损伤的影响。方法成年Wistar大鼠72只,体重200~250g,雌雄各半,随机分为3组(n=24):对照组(C组)、LPS组和二硫代氨基吡咯烷组(PDTC组)。LPS组腹腔注射LPS 8mg/kg;PDTC组尾静脉注射二硫代氨基吡咯烷120mg/kg,30min后腹腔注射LPS 8mg/kg;C组注射等量生理盐水。分别于注射LPS后1、3.6、12h时,腹腔注射2%戊巴比妥钠40mg/kg麻醉大鼠,下腔静脉取血样后处死,开胸取心脏,采用ELISA法测定血清肌钙蛋白T(cTnT)浓度,免疫组化法检测心肌组织Toll样受体4(TLR4)的表达和NF-κB p65的活性;光镜下观察心肌组织病理学结果。结果与C组比较,LPS组和PDTC组各时点血清cTnT浓度升高,心肌组织TLR4表达上调,NF-κB p65活性升高(P〈0.01);与LPS组比较,PDTC组各时点血清cTnT浓度下降,心肌组织NF—κB p65活性降低,注射LPS后6、12h时心肌组织TLR4表达下调(P〈0.01),病理学损伤减轻。结论二硫代氨基吡咯烷可减轻LPS诱发大鼠心肌损伤,其机制可能与抑制心肌组织NF-κB的活性和TLR4的表达有关。 Objective To investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) pretreatment on myocardium against endotoxin-induced injury in rats. Methods Seventy-two Wistar rats of both sexes weighing 200-250 g were randomly divided into 3 groups ( n=24 each) : group Ⅰ normal control (group C) ; group Ⅱ LPS and group Ⅲ PDTC. Eudotoxemia was induced by intraperitoneal LPS 8 mg/kg in group Ⅱ and Ⅲ . In group Ⅲ PDTC 120 mg/kg was injected iv at 30 min before IP LPS. Venous blood samples were collected at 1, 3, 6, 12 h after LPS administration for determination of serum cTnT concentration by ELISA. Six animals were killed at each time point after blood sample collection. Myocardial specimens were obtained for microscopic examination and determaintion of TLR4 expression and NF-κB p65 activity by immuno-histochemistry. Results Intrapefitoneal LPS significantly increased serum cTnT concentration and myocardial TLR4 expression and NF-κB p65 activity in group Ⅱ. PDTC pretreatment significantly attenuated LPS-induced increase in serum cTnT concentration and myocardial TLR4 expression and NF-κB p65 activity. Myocardial damage induced by LPS was also ameliorated by pretreatment with PDTC. Conclusion Pyrrolidine dithiocarbamate pretreatment can protect myocardium against LPS-induced injury through inhibition of activation of myocardial NF-κB p65 and expression of TLR4.
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2010年第2期213-215,共3页 Chinese Journal of Anesthesiology
基金 甘肃省自然科学研究基金(0710RJZA038)
关键词 吡咯烷类 硫代氨基甲酸酯类 内毒素类 心肌再灌注损伤 Pyrrolidines Thiocarbamates Endotoxins Myocardial reperfusion injury
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