羟乙基淀粉对兔缺血-再灌注心肌的保护作用

Protective effects of hydroxyethyl starch on myocardial ischemia/reperfusion injury in rabbits

目的观察羟乙基淀粉（HES130／0．4）对兔心肌缺血．再灌注损伤的白细胞介素-8（IL-8）、内皮素-1（ET-1）和髓过氧化物酶（MPO）活性的影响，探讨其可能的保护机制。方法36只大白兔随机分为乳酸林格氏液组（A组，n=12）；白蛋白组（B组，n=12）；羟乙基淀粉组（C组，n=12）。A，B，C三组再灌注前15min分别静脉注入6m;/kg乳酸林格氏液、5％人体白蛋白或6％羟乙基淀粉，于缺血前（I0）、缺血30min（11）、再灌注60min（R1）、180min（R2）四个时点采血，检测血清乳酸脱氢酶（LDH）、肌酸磷酸激酶（CPK）、白细胞介素-8（IL-8）和内皮素-1（ET-1）的浓度。再灌注180min处死大白兔测定心肌水含量、心肌梗死面积及髓过氧化物酶（MPO）活性。组间比较采用单因素方差分析（SNK—q检验），采用SPSS12．0统计软件处理，以P〈0．05为差异有统计学意义。结果三组血清LDH，CPK，IL-8和ET-1随再灌注时间延长而逐渐升高，在R时点，C组增高的程度明显低于A组[（181±17）U／LVS．（334±39）U／L；（1927±205）U／LVS．（2987±326）U／L；（5．03±1．16）ng／LVS．（6．96±1．21）ng／L；（380．9±78．4）ng／Lvs．（667．2±82．1）ng/L，P〈0．05]和B组[（181±17）U／Lvs．（320±38）U／L；（1927±205）U／Lvs．（2218±290）U／L；（5．03±1．16）ng／Lvs．（5．90±1．03）ng／L；（380．9±78．4）ng／Lvs．（615．6±80．2）ng／L，P〈0．05]；C组缺血区MPO活性（0．20±0．09）ng／L明显低于A组（0．48±0．15）ng/L和B组（0．37±0．12）．g／L（P〈0．05）；C组的心肌含水量（76±8．23）％和心肌梗死面积（11．53±1．02）％分别显著低于A组[（86±5．66）％，（26．48±2．33）％]和B组[（82±6．42）％，（19．76±4．32）％]（P〈0．05）。结论羟乙基淀粉对通过抑制IL-8及ET-1的生成和释放，降低缺血区MPO活性和毛细血管通透性，对缺血-再灌注损伤的心肌具有保护作用。

Objective To observe the effects of hydroethyl starch （HES130/0.4） on serum interleukin-8, endothelin-1 （ET-1） and myocardial myeloperoxidase activity （MPO） in rabbits subjected to isehemia-repeffusion, and to explore its possible mechanism. Method Thirty-six rabbits were randomly divided into three groups： lactated Ringer＇s solution group （group A, n = 12）, 5% human albumin group （group B, n = 12） and 6% hydroethyl starch group （group C, n = 12） The myodardial ischemia/reperfusion （MI/R） model was established by damping left anterior descending coronary artery for 30 minutes followed by repeffusion for 180 minutes. Fifteen minutes prior to rcpeffusion, animals of these 3 given groups were ifused vis right internal jugular vein with 6 mL/kg lactated Ringer＇ solution, 5% human albumin and hydroethyl starch, respectively. Blood samples were obtained before occlusion （I0）, 30 minutes after occlusion （I1）, 60 minutes （R1） and 180 （R2） minutes after reperfusion to determine the activities of serum lactate dehydrogenase （LDH）, serum creatine phosphokinase （CPK）, serum interleukin-8 （IL-8） and endothelin-1 （ ET-1 ）. The size of myocardial infarction （MI）, myocardial water content and myoloperoxidase activity （MPO） were examined as well. Statistical analyses were performed by using SPSS 12.0 software. Multiple comparisons were analyzed by using one-way analysis of variance （ SNK-q test）. P 〈0.05 was considered statistically significant. Results The serum LDH, CPK, IL-8 and ET-1 were gradually increased after reperfusion, however, 180 min after reperfusion all serum biomarkers in 6% hydroethyl starch group （group C） were significantly lower than those in lactated Ringer＇s solution group （group A） [（181± 17） U/1 vs. （334± 39） U/L; （1927 ±205） U/L vs. （2987 ± 326） U/L; （5.03 ± 1.16） ng/L vs. （6.96 ± 1.21 ） ng/L; （380 ± 78.4）mg/L vs. （667.2 ± 82.1 ） ng/L. all P 〈 0.05 ], and than those in 5 % human albumin group （group B） [（181 ±17） U/L vs. （320±38） U/L; （1727±205） U/L vs. （2218±290） U/L; （5.03 ± 1.16） ng/L vs. （5.90± 1.03） ng/L; （380.9±78.4） ng/L vs. （615.6±80.2） ng/L, allP 〈0.05]. The activity of MPO of ischemic area in group C （0.20 ± 0. 09 ng/L） was significantly lower than that in group A （0.48 ± 0. 15 ng/L） and in group B （0.37 ± 0.12 ng/L） （ P 〈 0. 05）. Myocardial water content and infarct size of heart found in group C were significantly smaller than those in both group A and group B （P 〈 0. 05）. Conclusions The 6% hydi＇oethyl starch exhibits its protective effects on myocardial ischemia-reperfusion injury by preventing the production and release of serum IL-8 and ET-1, decreasing neutrophil infihration capillary permeability and improving microvascular circulation.