盐酸戊乙奎醚后处理对大鼠肢体缺血再灌注损伤的影响  

Effects of penehyclidine hydrochloride postconditioning on hind limb ischemia-reperfution injury in rats

作　　者：汪涛[1] 冷玉芳[1] 张悦[1] 薛兴[1] 张艳[1] 康于庆[1] 

机构地区：[1]兰州大学第一医院麻醉科,730000

出　　处：《中华麻醉学杂志》2010年第11期1367-1371,共5页Chinese Journal of Anesthesiology

基　　金：基金项目：兰州市科技发展计划项目（2009-1-52）

摘　　要：目的 探讨盐酸戊乙奎醚后处理对大鼠肢体缺血再灌注损伤的影响.方法 成年雄性Wistar大鼠144只,体重220～250 g,随机分为4组（n=36）：对照组（C组）、缺血再灌注组（IR组）、缺血后处理组（IPO组）和盐酸戊乙奎醚后处理组（IPHC组）.IR组、IPO组和IPHC组采用弹力橡皮筋环扎大鼠双后肢近心端3 h,再灌注24 h的方法建立肢体缺血再灌注模型.再灌注即刻IPO组于双下肢近心端进行后处理,再灌注30 s、缺血30 s,重复3次;IPHC尾静脉注射盐酸戊乙奎醚0.15 mg/kg,用生理盐水稀释为1 m1.分别于再灌注即刻、1、3、6、12和24 h时,采集下腔静脉血样后,各放血处死大鼠6只,取后肢股四头肌组织,测定血清乳酸脱氢酶（LDH）和肌酸激酶（CK）的活性、TNF-α和IL-10含量,测定股四头肌组织MDA含量,SOD、氧化物酶（MPO）、Na＋-K＋-ATP酶和Ca2＋-Mg2＋-ATP酶的活性及HIF-1α表达,光镜下观察病理学结果.结果 与C组比较,IR组、IPO和IPHC组血清LDH、CK的活性和TNF-α、IL-10的浓度升高,股四头肌组织SOD、Na＋-K＋-ATP酶和Ca2＋-Mg2＋-ATP酶的活性降低,MPO活性和MDA含量升高,HIF-1α表达上调（P＜0.05或0.01）;与IR组比较,IPO组和IPHC组血清LDH、CK的活性和TNF-α浓度降低,IL-10浓度升高,股四头肌组织SOD、Na＋-K＋-ATP酶和Ca2＋-Mg2＋-ATP酶的活性升高,MPO活性和MDA含量降低,HIF-1α表达下调（P＜0.01）,病理学损伤减轻;与IPO组比较,IPHC组血清LDH活性和TNF-α浓度降低,CK活性和IL-10浓度升高,股四头肌组织SOD、MPO的活性和MDA含量降低,HIF-1α表达下调（P＜0.05或0.01）,Na＋-K＋-ATP酶和Ca2＋-Mg2＋-ATP酶的活性差异无统计学意义（P＞0.05）.结论 盐酸戊乙奎醚后处理可减轻大鼠肢体缺血再灌注损伤,其机制与其抑制炎性反应和脂质过氧化反应,减轻细胞内钙超载,改善细胞能量代谢等有关.Objective To investigate the effects of penehyclldine hydrochloride postconditioning on hind limb ischemia-reperfusion （I/R） injury in rats. Methods One hundred and forty-four male Wistar rats weighing 220-250 g were randomly divided into 4 groups （n = 36 each）： control group （group C）, I/R group, ischemic postconditioning group （group IPO） and penehyclidine hydrochloride postconditioning group （group PHPO）. Limb ischemia was induced by occlusion of bilateral hind limb for 3 h followed by 24 h reperfusion. In group IPO, the animals were subjected to three cycles of 30 s reperfusion and 30 s ischemia on the proximal part of the hind limb,while in group PHPO, the animals received iv injection of penehyclidine hydrochloride 0.15 mg/kg （in normal saline 1 wl） via the caudal vein immediately after reperfusion. Blood samples from the inferior vena cava were taken for determination of activities of serum LDH and CK and concentrations of TNF-α and IL-10 at O, 1, 3, 6, 12 and 24 h of reperfusion. Then 6 rats were sacrificed at each time point respectively and the quadriceps femoris tissues of the hind limb were removed for determination of MDA content, activities of SOD, MPO, Na＋ -K＋-ATPase and Ca2 ＋ - Mg2＋ -ATPase, and HIF- 1 α expression and microscropic examination. Results Compared with group C, the activities of serum LDH and CK and concentrations of TNF-α and IL-10 were significantly increased, the activities of SOD, Na＋-K＋-ATPase and Ca2＋-Mg2＋-ATPase were decreased, MPO activities and MDA content were increased, HIF-1α expression was up-regulated in group I/R, IPO and PHPO （P 〈0.05 or 0.01）. Compared with group I/R, the serum activities of serum LDH and CK and TNF-α concentration were significantly decreased, IL- 10concentration was increased, activities of SOD, Na＋ -K＋ -ATPase and Ca2＋ -Mg2＋ -ATPase were increased, and MPO activity and MDA content were decreased, HIF-1α expression was down-regulated （P 〈 0.01）, and the pathologic changes was reduc

关 键 词：奎宁环类 再灌注损伤 四肢 

分 类 号：R965[医药卫生—药理学]