活血化瘀注射液Ⅰ号预处理与缺血预处理改善肝缺血再灌注损伤  

Effects of Huoxue Huayu injection I pretreatment and ischemic preconditioning on liver ischemia and reperfusion injury in rats

作　　者：毕旭东[1] 郭伟[2] 赵晶[3] 赵连根[4] 付晓光[1] 

机构地区：[1]辽宁医学院附属第一医院肝胆外科,辽宁省锦州市121001 [2]山东省肿瘤医院放射科,山东省济南市250117 [3]辽宁医学院组织胚胎学教研室,辽宁省锦州市121001 [4]天津市中西医结合急腹症研究所,天津市300100

出　　处：《世界华人消化杂志》2007年第8期831-837,共7页World Chinese Journal of Digestology

摘　　要：目的:研究活血化瘀注射液I号(HHI-I)预处理与缺血预处理(ischemic preconditioning,IP)对大鼠肝脏缺血再灌注(ischemia and reperfusion, I/R)损伤的改善作用,并比较两者的作用效果．方法:健康♂SD大鼠80只,随机分为假手术对照组(Shaman)、缺血再灌注组(I／R组)、缺血预处理组(IP组)、HHI-I预处理组(HHI-I组),每组20只．建立大鼠部分肝缺血模型,各组在I／R后1,3,6,24 h分别取材,测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)的水平:取左肝测组织丙二醛(MDA)、超氧化物歧化酶(SOD)的含量．I／R后1 h RT- PCR检测肝组织中肿瘤坏死因子α(TNF-α)和细胞间黏附分子-1(ICAM-1)mRNA的表达, I／R后3 h行组织学观察．结果:I／R组、IP组、HHI-I组的ALT,AST, LDH活性、MDA值和TNF-α．ICAM-1 mRNA表达水平均明显高于Sham组．IP组、HHI-I组低于I／R组．HHI-I组所有时间点ALT,AST, LDH明显低于IP组(ALT:2378．8±303．4 nkat／L VS 2840．6±248．4 nkat／L;AST:2887．2±270．1 nkat／L vs 4567．6±275．1 nkat／L;LDH:10550．4±710．1 nkat／L vs 12164．1±735．1 nkat／L;P均<0．05)．HHI-I组MDA值明显低于IP组(17．35±1．39 nmol／g vs 21．66±1．84 nmol／g,P<0．05)．HHI-I组TNF-α,ICAM-1 mRNA表达水平低于IP组(TNF-α:0．54±0．06 vs 0．78±0．08; ICAM-1:0．43±0．03 vs 0．69±0．11,P均<0．01)．各组SOD值均低于Sham组(P<0．05)．IP组、HHI-I组均高于I／R组(P<0．05),HHI-I组SOD(1．3,6 h)明显高于IP组(136．00±12．50 nmol/gvs 124．70±9．32 nmol／g,P<0．05)．Sham组光镜下肝小叶结构正常;I/R组肝小叶结构紊乱,肝细胞水肿变性;IP组肝细胞水肿明显,部分肝细胞变性;HHI-I组肝小叶结构基本正常,肝细胞无明显水肿．结论:HHI-I预处理与IP均可改善I／R对肝脏造成的损伤,前者的效果优于后者．HHI-I的保护机制可能在于改善肝脏微循环,减轻组织缺氧状态,并通过抑制TNF-α和ICAM-1等细胞因子和细胞黏附�AIM： To investigate the effects of Huoxue Huayu injection Ⅰ （HHI-Ⅰ） pretreatment and ischemic preconditioning （IP） on hepatic ischemia and reperfusion （I/R） injury in rats and compare their efficacity. METHODS： Eighty healthy adult male Sprague-Dawley rats were randomly and averagely divided into 4 groups： sham operation （SO） group, I/R group, ischemia preconditioning （IP） group, and HHI-Ⅰ pretreatment group. After partial hepatic I/R model was made, the rats of each group were sacrificed to determine serum alanine aminotransferase （AST）, alanine aminotransferase （ALT）, lactate dehydrogenase （LDH）, tissue malondialdehyde （MDA） and superoxide dismutase （SOD） level 1, 3, 6 and 24 hours after reperfusion, respectively. Tissue tumor necrosis factor alpha （TNF-α） and intercellular adhesion molecule-1 （ICAM-1） mRNA levels were determined by reverse transcription-polymerase chain reaction after 1 hour of reperfusion. Liver histology was observed after 3 hours of reperfusion. RESULTS： The activities of ALT, AST, LDH, the level of MDA, and the expression of TNF-α, ICAM-1 mRNA in I/R, IP, and HHI-Ⅰ group were significantly higher than those in SO group, but they were markedly lower in IP and HHI-Ⅰ group than those in I/R group. The activities of ALT, AST, LDH in HHI-Ⅰ group were significantly lower than those in IP group （ALT： 2378.8 ± 303.4 nkat/L vs 2840.6 ± 248.4 nkat/L; AST： 2887.2 ± 270.1 nkat/ L vs 4567.6 ± 275.1 nkat/L; LDH： 10550.4 ± 710.1 nkat/L vs 12164.1 ± 735.1 nkat/L; all P 〈 0.05）. As compared with that in the IP group, the level of MDA in HHI-Ⅰ group was decreased at the 3^rd and 6^th hour 07.35 ± 1.39 nmol/g vs 21.66 ± 1.84 nmol/g, P 〈 0.05）, and the mRNA expression of TNF-α and ICAM-1 were decreased （TNF-α： 0.54 ± 0.06 vs 0.78 ± 0.08; ICAM-I： 0.43 ± 0.03 vs 0.69 ± 0.11, both P 〈 0.01）. The level of SOD in I/R, IP and HHI-Ⅰ group was markedly lower than that in SO group （P 〈 0.05）, but it

关 键 词：肝脏缺血再灌注损伤 缺血预处理 肿瘤坏死因子-Α 活血化瘀注射液Ⅰ号 大鼠 

分 类 号：R285.5[医药卫生—中药学]