己酮可可碱对重度失血性休克大鼠再灌注后肝损伤的影响  

Treatment with pentoxifylline reduces ischemia/reperfusion-induced liver injury in rats with severe hemorrhagic shock

作　　者：陆化梅[1] 耿智隆[2] 赵峰[2] 杨木强[2] 

机构地区：[1]兰州大学第二临床医学院麻醉系,甘肃省兰州市730050 [2]中国人民解放军兰州军区兰州总医院麻醉科,甘肃省兰州市730050

出　　处：《世界华人消化杂志》2011年第3期227-232,共6页World Chinese Journal of Digestology

基　　金：全军"十一五"面上基金资助项目;No.06MA083~~

摘　　要：目的:研究已酮可可碱(PTX)对重度失血性休克大鼠再灌注后肝损伤的影响,并探讨其可能的作用机制.方法:48只SD大鼠随机分为4组:对照组(C组)、单纯休克组(NR组)、乳酸林格氏液组(LR组)、乳酸林格氏液联合PTX组(LRPTX组).复制重度失血性休克模型,连续检测MAP的变化.LR及LRPTX组以3倍失血量LR/LRPTX(PTX25mg/kg)液复苏.各组分别于休克前、休克1h及复苏4h时间点测谷丙转氨酶(ALT)及谷草转氨酶(AST).NR组在休克1h处死大鼠,LR组、LRPTX组及C组在复苏4h处死大鼠,取肝组织检测TNF-α、NF-κB、巨噬细胞炎性蛋白-2(MIP-2)的蛋白表达及髓过氧化物酶(MPO)活性.电镜及光镜下观察肝组织病理变化.结果:与C组比较,各组大鼠休克1hMAP(mmHg)降低(37.3±2.1,37.0±2.0,37.6±2.2vs106.0±2.6,均P<0.05),液体复苏后MAP上升,LR及LRPTX组复苏后3h及4h时间点,MAP(mmHg)下降(88.3±3.0,87.6±4.3vs105.0±2.9;69.0±2.0,66.7±2.1vs102.1±1.1,均P<0.05).与C组比较,其他各组血中AST(U/L)(142.0±8.3,144.1±7.6,147.2±8.1vs45.1±6.3;427.0±12.5,365.3±8.0vs51.1±6.3,均P<0.01)及ALT(U/L)明显升高(86.3±7.8,88.3±6.6,89.1±5.9vs53.6±6.1;342.9±4.7,280.4±9.1vs50.6±7.6,均P<0.05);肝组织TNF-α、NF-κB及MIP-2的蛋白表达明显升高,MPO活性增加(均P<0.05),肝组织病理学损伤明显;与LR组比较,LRPTX组复苏后4h血中AST及ALT明显降低(均P<0.05),TNF-α、NF-κB及MIP-2的蛋白含量明显下降,MPO活性降低(均P<0.05),肝组织病理学损伤减轻.结论:PTX通过减少TNF-α的释放,抑制NF-κB的活化,下调趋化因子的表达,减轻失血性休克再灌注后肝组织损伤.AIM： To investigate the effects of treatment with pentoxifylline （PTX） on ischemia/reperfusion- induced liver injury in rats with severe hemor- rhagic shock. METHOOS： Forty-eight Sprague-Dawley rats were randomly and equally divided into four groups： control group, shock group （NR group）, Lactated Ringer＇s （LR） solution-treated group （LR group）, LR solution plus PTX group （LR- PTX group）. A rat model of severe hemorrhagic shock was generated, and arterial blood pressure（MAP） was determined continuously. Blood specimens were collected before shock and 1 and 4 h after resuscitation for determination of serum AST and ALT levels. The rats of the NR group were killed 1 h after shock to collect liver samples. The rats of the LR and LR-PTX groups were resuscitated with LR and LR-PTX （25 mg/kg, three times the volume of shed blood）, respectively, and then killed 4 h after resuscita- tion to collect liver samples to determine the expression of TNF-α, NF-κB and MIP-2 proteins and MPO activity. Liver injury was examined by light microscopy and electron microscopy. RESULTS： Compared with the control group, MAP （mmHg） decreased significantly 1 h after shock in the other groups （37.3 ± 2.1, 37.0 ± 2.0, 37.6 ± 2.2 vs 106.0 ± 2.6, all P 〈 0.05）. After resuscitation, MAP rose initially but decreased at 3 and 4 h in the LR and LR-PTX groups （88.3 ± 3.0, 87.6 ± 4.3 vs 105.0 ± 2.9; 69.0 ± 2.0, 66.7 ± 2.1 vs 102.1 ± 1.1, P 〈 0.05）. Serum AST and ALT levels at 1 h after shock and 4 h after resuscitation in the NR, LR and LR-PTX groups were significantly higher than those in the control group （142.0 ± 8.3, 144.1 ± 7.6, 147.2 ± 8.1 vs 45.1 ± 6.3; 427.0 ± 12.5, 365.3 ± 8.0 vs 51.1 ± 6.3, all P 〈 0.01; 86.3 ± 7.8, 88.3 ± 6.6, 89.1 ± 5.9 vs 53.6 ± 6.1; 342.9 ± 4.7, 280.4 ± 9.1 vs 50.6 ± 7.6, all P 〈 0.05）. The expression of NF-κB, TNF-α and MIP-2 proteins and MPO activity in the liver were significantly increased and pathologic injury was more signifi

关 键 词：失血性休克 肝损伤 复苏 己酮可可碱 

分 类 号：R605.971[医药卫生—急诊医学]