稳定微管减少心肌缺血再灌注损伤

Experimental research on stabilizing microtubules to decrease myocardial injury

目的探讨稳定微管能否减少心肌缺血再灌注损伤。方法 (1)将离体大鼠心脏分为对照组、缺血组、缺血+0.1μmol/L泰素和缺血+1μmol/L泰素组(n=15)。每组先给予15 min平衡后,对照组继续给予50 min常氧灌注;缺血组给予20 min常氧灌注+30 min缺血处理;缺血+0.1μmol/L(或1μmol/L)泰素组给予20 min常氧灌注,30 min缺血处理,整个过程中均给予0.1μmol/L(或1μmol/L)泰素灌流。比较各组心律失常情况,观察微管形态结构并进行断裂评分。(2)将离体大鼠心脏分为正常对照组、缺血再灌注组和1μmol/L泰素组(n=8)。缺血再灌注组进行Langendorff灌流,结扎左前降支30 min,再灌注120 min;1μmol/L泰素组给予1μmol/L进行灌流,其余处理同缺血再灌注组。灌流结束即刻冠脉内灌入伊文思蓝进行染色,比较各组心肌梗死面积。结果 (1)0.1和1μmol/L泰素均能有效降低缺血性室性心律失常的发生,降低室性心律失常评分,且呈剂量依赖性(P<0.05);并均能降低室性心动过速的发生率(P<0.05)。(2)0.1μmol/L泰素灌流能降低微管断裂评分。(3)1μmol/L泰素灌流能明显缩小缺血再灌注心脏梗死区面积(P<0.05)。结论稳定微管能减少心肌缺血再灌注损伤。

Objective To study whether stabilizing microtubules can decrease myocardial ischaemic-reperfusion injury. Methods （1） The isolated rat hearts were divided into four groups （n=15）： control group, ischemie group, ischemic＋0.1 μmol/L Taxol group, and ischemic＋l ptmol/L Taxol group. All the groups were given a 15-min equilibration and then followed by different treatments： control group, 50 min normoxic superfusion ischemia group, 20 rain normoxie superfusion plus 30 min ischemia; and Taxol groups, 20 min normoxic superfusion plus 30 min ischemia, plus 0. 1 or 1 /mμol/L Taxol throughout 50- min superfusion period. Arrthymias scores were assessed and compared between different groups; the structure of the mierotubules was observed and its breakage score was obtained. （2） The isolated rat hearts were divided into 3 groups （n=8） ： normal control group, ischemic/reperfusion （I/R） group, and l ptmol/L Taxol group. The I/R group was Langendorffperfused; the left anterior descending branch was ligated for 30 min and reperfused for 120 min. The Taxol group received 1μmol/L Taxol and other treatments were similar to the I/R group. Evans blue perfusion was used to observe the infarct size of each group. Results Stabilizing microtubules with Taxol （0.1 /μmol/L or 1 tμmol/L） reduced ischaemic ventrieular arrhythmia in a dose-dependent fashion （P μ 0. 05）; it also significantly reduced arrhythmia scores and the incidence of ventricular tachycardia （Pμ0.05）. Taxol at 0. 1 μmol/L greatly decreased mierotubule breakage score, and at 1 tμmol/L significantly reduced the infarct size compared with the control group （P μ 0. 05）. Conclusion Stabilizing microtubules can reduce myocardial ischaemic-reperfusion injury.