三七三醇皂苷通过PI3K/Akt通路减轻大鼠离体心脏缺血/再灌注损伤的研究  

The study of panax notoginseng saponins through PI3K/Akt pathway to reduce ischemia/reperfusion injury in isolated rat hearts

作　　者：文超 王子杨 鲁卫星 Wen Chao;Wang Ziyang;Lu Weixing(Department of Vasculocardiology,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学第三附属医院心内科

出　　处：《疑难病杂志》2020年第10期1042-1047,共6页Chinese Journal of Difficult and Complicated Cases

基　　金：北京市自然科学基金项目(7172124)。

摘　　要：目的探讨三七三醇皂苷(PTS)对心肌缺血/再灌注(I/R)大鼠心肌功能及磷酸肌醇—蛋白激酶B(PI3K/Akt)信号通路的影响。方法将40只雄性Wistar大鼠随机数字表法分为5组,每组8只。对照组、I/R组、PTS组、LY294002组、LY294002+PTS组,通过Langendorff离体心脏灌流装置建立心脏缺血/再灌注模型,收集不同时刻的灌流液测量心肌酶学指标(CK-MB、LDH),并记录不同时刻左心室血流动力学参数(HR、LVESD、LVEDD、LVDP、±dp/dtmax);Western-blot检测心肌组织中Akt、p-Akt、GSK-3β、p-GSK-3β的表达,免疫组化检测Bax、Bcl-2、Caspase-3的表达。结果(1)血流动力学参数:对照组HR不同时点无明显变化(P>0.05),其余各组均不同程度上升,且除对照组外其余4组在再灌注75 min时无明显差异(P>0.05)。对照组不同时点LVESP、LVEDP、LVDP、±dp/dt max无明显变化,其余各组随时间延长出现不同程度下降。再灌注75 min时,PTS组明显低于模型组(P<0.05),而LY294002+PTS组与模型组无明显差异,与PTS组差异显著(P<0.05)。(2)CK-MB、LDH:对照组不同时点无显著变化,其余各组再灌注后心肌酶水平均较缺血30 min有显著提升(P<0.05)。各组平衡20 min时无明显差异(P>0.05);局部缺血30 min时,各组CK-MB无统计学差异(P>0.05),而各组LDH较对照组有所升高(P<0.05);再灌注15min、75 min时,各组均较对照组明显升高,PTS组明显低于模型组,LY294002+PTS组高于PTS组(P均<0.05)。(3)Akt、pAkt、GSK-3β、pGSK-3β的表达:缺血再灌注损伤后,各组心肌组织Akt、GSK-3β表达无统计学差异(P>0.05),pAkt、pGSK在PTS组中表达较模型组有显著提高(P<0.05),在应用LY294002的2组中表达较模型组显著下降(P<0.05),且LY294002+PTS与PTS组差异存在统计学意义(P<0.05)。(4)Bax、Bcl-2、Caspase-3的表达:模型组Bax、Caspase-3显著高于对照组(P<0.05),PTS与LY+PTS 2组Bax、Caspase-3表达低于模型组(P<0.05)。对照组Bcl-2强阳性,模型组显著低于对照组(P<0.05Objective To explore the effect of notoginseng triol saponins(PTS)on myocardial function and PI3K/Akt signaling pathway in myocardial ischemia/reperfusion(I/R)rats.Methods Forty male Wistar rats were randomly divided into 5 groups with 8 rats in each group.In the control group,I/R group,PTS group,LY294002 group,LY294002+PTS group,the Langendorff isolated cardiac perfusion device was used to establish a cardiac ischemia/reperfusion model,and the perfusion fluid at different times was collected to measure myocardial enzyme indexes(CK-MB,LDH),and record left ventricular hemodynamic parameters(HR,LVESD,LVEDD,LVDP,±dp/dtmax)at different moments;Western blot detection of Akt,pAkt,GSK-3β,pGSK-3βexpression in myocardial tissue,immune Histochemical detection of Bax,Bcl-2,Caspase-3 expression.Results(1)Hemodynamic parameters:the HR of the control group did not change significantly at different time points(P>0.05),the other groups increased to varying degrees,and the remaining four groups except the control group had no significant difference at 75 minutes of reperfusion(P>0.05).There was no significant change in LVESP,LVEDP,LVDP,±dp/dt max in the control group at different time points,and the other groups decreased to varying degrees over time.At 75 minutes of reperfusion,the PTS group was significantly lower than the model group(P<0.05),while the LY294002+PTS group was not significantly different from the model group,but was significantly different from the PTS group(P<0.05).(2)CK-MB,LDH:The control group did not change significantly at different time points,and the myocardial enzyme levels in the other groups were significantly increased after reperfusion compared with 30 min ischemia(P<0.05).There was no significant difference between the groups at 20 min of equilibrium(P>0.05);at 30 min of ischemia,there was no statistical difference between the CK-MB groups(P>0.05),while the LDH groups were higher than the control group(P<0.05);at 15min and 75min of reperfusion,all groups were significantly higher than the control

关 键 词：三七三醇皂苷 缺血/再灌注 Langendorff离体心脏 磷酸肌醇—蛋白激酶B信号通路 

分 类 号：R285.5[医药卫生—中药学]