虎杖苷通过PKC对大鼠离体缺血再灌注心肌的保护作用

目的:研究虎杖苷(polydatin,PD)对大鼠离体缺血/再灌注(I/R)心肌的保护作用。方法:将40只SD大鼠随机分为4组,包括I/R组,PD(I/R+PD)组,虎杖苷+蛋白激酶C(PKC)阻断剂(I/R+PD+chelerythrine)组和PKC阻断剂(I/R+chelerythrine)组。采用Langendorff灌流法建立离体心肌I/R模型,缺血40 min,再灌注共40 min,分别测量再灌20 min以及再灌40 min时心功能和酶学指标包括:心率、左室收缩压(LVDP)、左室舒张末压(LVEDP)、心室内压最大变化速率(±dp/dtmax)及磷酸激酶(PK)、乳酸脱氢酶(LDH)浓度。结果:心肌I/R可引起心脏功能I/R+PD组±dp/dtmax的恢复率明显回升(P0.05),同时,LVEDP、LVDP等指标也有明显改善(P0.05),LDH、PK浓度在复灌20和40 min时明显低于I/R组(P0.05)。说明PD能部分抑制再灌注期PK和LDH的漏出。PD还能够显著提高I/R心肌的超氧化物歧化酶(SOD)水平,并且降低丙二醛(MDA)水平,发挥心肌保护作用。应用PKC抑制剂chelerythrine则可以消除PD的上述作用。结论:PD可能通过PKC蛋白信号转导通路对I/R心肌发挥保护作用。

Myocardial protective effects of polydatin on isolated rat hearts suffering from ischemia/reperfusion via PKC dependent pathway

AIM: To investigate myocardial protective effects of the polydatin (polydatin, PD) on ischemia-reperfused rat hearts in vitro. METHODS: Forty SD rats were randomly divided into four groups: ischemia-reperfusion group (I/R group), PD group (I/R+PD group), polydatin+protein kinase C(PKC) inhibitor group (I/R+PD+CHE group) and PKC inhibitor group (I/R+CHE group). The isolated rat heart was perfused at a Langendorff apparatus and ischemia 40 min and reperfusion 40 min were performed. The heart function parameters, including heart rate, left ventricular systolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal velocity of increase and decrease of ventricular pressure (±dp/dtmax), and the concentration of phosphate kinase (PK) and lactate dehydrogenase (LDH) were analyzed at different time points (20 min and 40 min after reperfusion). RESULTS: Myocardial ischemia and reperfusion resulted in myocardial injuries. LVDP and LV±dp/dtmax decreased while LVEDP increased in I/R group, with increases in PK and LDH leakage and MDA level and decreases in SOD level. The changes in the abovementioned cardiac functions, myocardial enzyme activity and MDA or SOD level were significantly attenuated in I/R+PD group (P<0.05). The effects of PD were abolished by CHE, a selective PKC inhibitor. CONCLUSION: PD plays a protective role in ischemia-reperfusion myocardium and the cardioprotective effect of PD maybe via PKC dependent signaling pathway.