目的 观察丙泊酚对大鼠急性心肌缺血再灌注(ischemia/reperfusion, I/R)损伤中微管相关蛋白1轻链3（microtubule-associated protein 1 light 3, LC3）的影响，探讨丙泊酚心肌保护的可能机制。方法 采用大鼠在体心肌I/R损伤模型，84只雄性大鼠采用随机数字表法分为6组（n=14）：假手术组（Sham组）、缺血再灌注组（I/R组）、脂肪乳组（Int组）、丙泊酚低剂量组（P1组）、中剂量组（P2组）、高剂量组（P3组）。除Sham组外，其余各组均缺血30min，再灌注2h。Int、P1、P2、P3组分别依次经股静脉输注脂肪乳2.4 ml•kg-1•h-1、丙泊酚6、12、24 mg•kg-1•h-1。连续记录功能学指标； 2,3,5-氯化三苯基四氮唑（2,3,5-triphenyltetrazolium chloride，TTC）染色法检测心肌梗死面积，酶标仪法测定乳酸脱氢酶（lactate dehydrogenase, LDH）的活性，western blot分析LC3、p-Akt和Akt的表达水平。结果 与I/R组相比，P1、P2、P3组心功能明显改善，心肌梗死面积[(33.78±2.73)%、(27.13±1.89)%和(36.15±3.22)% vs (50.32±4.24)%, P<0.05]和血浆LDH水平都显著降低，心肌损伤减轻，LC3II/LC3I比率[(0.97±0.03)、(0.76±0.08)和(0.93±0.04) vs (1.15±0.07), P<0.05]减低，p-Akt表达[(1.69±0.43)、(2.51±0.15)和(1.95±0.41)vs (1.00±0.13), P<0.05]增加，而Int组则差异没有统计学意义（P>0.05）；与P1组相比，P2组心功能明显改善，心肌梗死面积[(27.13±1.89)% vs (33.78±2.73)%, P<0.05]和血浆LDH水平均显著降低，心肌损伤更轻，LC3II/LC3I比率[ (0.76±0.08) vs (0.97±0.03), P<0.05]减低，p-Akt表达[(2.51±0.15) vs (1.69±0.43), P<0.05]增加，而P3组差异没有统计学意义（P>0.05）。结论 丙泊酚通过抑制LC3的表达，对心肌发挥保护作用，且可能与PI3K/Akt信号通路有关。
Objective To study the effect of propofol on the production of LC3 following acute myocardial ischemia-reperfusion injury of rats, and the possible mechanism of that. Methods The in vivo rat myocardial I/R injury model was developed. 84 male rats were randomly divided into Sham group(Sham), ischemia-reperfusion group(I/R), intralipid group(Int), low dose propofol group(P1), middle dose propofol group(P2), and high dose propofol group(P3). Each group underwent 30 min ischemia and 2 h reperfusion except Sham group. Intralipid 2.4ml•kg-1•h-1 and propofol 6, 12, 24 mg•kg-1•h-1 were infused iv in the last four groups separately. Hemodynamic parameters were monitored continuously．Myocardial infarct size and lactate dehydrogenase (LDH) levels were examined by 2，3，5-triphenyltetrazolium chloride(TTC) staining and enzyme standard method，respectively. Expressions of LC3, p-Akt, and Akt were determined by Western blot. Results Compared with I/R group, cardiac function was improved(P<0.05) in P1, P2 and P3 group. Myocardial infarct size[(33.78±2.73)%、(27.13±1.89)%和(36.15±3.22)% vs (50.32±4.24)%, P<0.05], LDH levels of plasma and ratio of LC3II/LC3I [(0.97±0.03)、(0.76±0.08)和(0.93±0.04) vs (1.15±0.07), P<0.05]were decreased respectively in the three groups, while the expression of p-Akt[(1.69±0.43)、(2.51±0.15)和(1.95±0.41)vs (1.00±0.13), P<0.05] was increased, compared with I/R group. There was no difference between I/R and Int group(P>0.05). Compared with P1 group，cardiac function was significantly improved(P<0.05)，the expression of p-Akt [(2.51±0.15) vs (1.69±0.43), P<0.05]was increased, with the myocardial infarct size[(27.13±1.89)% vs (33.78±2.73)%, P<0.05], LDH levels of plasma and ratio of LC3II/LC3I [ (0.76±0.08) vs (0.97±0.03), P<0.05]significantly lower than that of P1 group, while no difference in P3 group(P>0.05). Conclusion Propofol could inhibit I/R- induced activation of LC3 to reduce I/R injury , and may be related to PI3K/Akt pathway.
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