摘要
目的观察丙泊酚(propofol,P)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(micmtubule-associated protein 1 light3,LC3)的影响,探讨P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sD大鼠采用随机数字表法分为6组:假手术组(Sham组)、I/R组、脂肪乳组(Int组)、P低剂量组(P1组)、P中剂量组(P2组)、P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2.4ml·kg^-1·h^-1、P6、12、24mg·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-trigIhenyhetrazoliumchloride,TYC)染色法检测心肌梗死面积,酶标仪法测定乳酸脱氢酶(1actatedehydrogenase,LDH)的活性,Westemblot分析LC3、磷酸化蛋白激酶B(p-Akt)和蛋白激酶B(Akt)的表达水平。结果与YR组比较,P1、P2、P3组心功能明显改善,心肌梗死面积[(33.8±2.7)%、(27.1±1.9)%和(36.2±312)%VS(50.3±4.2)%,P〈O.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组则差异无统计学意义(P〉0.05);与P1组比较,P2组心功能明显改善,心肌梗死面积[(27.1±1.9)%VS(33.8±2.7)%,P〈0.05]和血浆LDH水平均显著降低,心肌损伤更轻,LC311/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P通过抑制LC3的表达,对心肌发挥保护作用,且可能与磷脂酰肌醇-3激酶�
Objective To study the effect of propofol(P) on the expression of microtubule-associated protein 1 light 3(LC3) following acute myocardial ischemia/reperfusion (I/R)injury of rats, and the possible mechanism of P for myocardial protection. Methods The in vivo rat myocardial I/R injury model was developed. Eighty-four male rats were randomly divided into Sham group (Sham), I/R group, intralipid group (Int), low-dose P group (P1), middle-dose P group (P2), and high-dose P group (P3). Each group underwent 30 min ischemia and 2 h reperfusion except Sham group. Intralipid 2.4 ml·kg^-1·h^-1 and P 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 (TIC) 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 groups. Myocardial infarct size[(33.8+2.7)%, (27.1±1.9)% and (36.2± 3.2)% vs (50.3±4.2)%, P〈0.05], the LDH levels in plasma and ratio of LC3 II/LC3 I [(0.97±0.03), (0,76±0.08) and (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 ) and (1.95±0.41) vs (1.00±0.13), P〈0.05] was increased. 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 [ (27.1±1.9)% vs (33.8±2.7)%, P〈0.05], LDH levels in plasma and ratio of LC3 11/LC3 II(0.76±0.08) vs (0.97±0.03), P〈0.053 significantly lower than that of P1 group, while there was no difference in
出处
《国际麻醉学与复苏杂志》
CAS
2014年第3期198-202,共5页
International Journal of Anesthesiology and Resuscitation
关键词
丙泊酚
心肌
再灌注损伤
自噬
微管相关蛋白1轻链3
磷脂酰肌醇-3-激酶
Propofol
Myocardium
Reperfusion injury
Autophagy
Microtubule-associated protein 1 light chain 3
Phosphatidylinositol 3-kinase