2021 年第 2 期 第 16 卷

三七三醇皂苷对大鼠离体心脏缺血再灌注损伤的作用研究

Effects of panaxatriol saponins on ischemia-reperfusion injury in isolated-rat heart

作者：文超1王子杨2鲁娜3鲁卫星1

英文作者：Wen Chao1 Wang Ziyang2 Lu Na3 Lu Weixing1

单位：1北京中医药大学第三附属医院心内科100029；2北京中医药大学第二临床医学院100029；3济南市章丘区人民医院医保科250200

英文单位：1Department of Cardiology Beijing University of Chinese Medicine Third Affiliated Hospital Beijing 100029 China; 2the Second Clinical Medical College， Beijing University of Chinese Medicine Beijing 100029 China; 3Department of Medical Insurance Zhangqiu District People′s Hospital Jinan 250200 China

关键词：缺血再灌注；三七三醇皂苷；Langendorff离体心脏

英文关键词：schemia-reperfusion;Panaxatriolsaponins;Langendorffisolated-heart

• 摘要：

• 目的 建立Langendorff离体心脏局部缺血再灌注(IR)模型，探讨三七三醇皂苷对大鼠离体心脏IR损伤的作用。方法 将40只健康雄性Wistar大鼠随机分为对照组、IR模型组和低、中、高剂量三七三醇皂苷组（PTSL组、PTSM组、PTSH组）,各8只。对照组只穿线不结扎冠状动脉左前降支近分支，以K-H液持续灌流105 min；IR模型组穿线结扎冠状动脉左前降支近分支处30 min后开放结扎线，K-H液复灌75 min；PTSL组、PTSM组、PTSH组穿线结扎冠状动脉左前降支近分支处30 min后，分别给予含5、10、20 mg/L三七三醇皂苷的K-H液复灌75 min。收集5组大鼠平衡灌注20 min、局部缺血30 min和再灌注15、75 min的灌流液，检测肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH）水平。比较5组平衡灌注20 min、局部缺血30 min和再灌注15、75 min通过多导生理仪记录的心脏血流动力学参数水平，包括心率、左心室收缩末压（LVESP）、左心室舒张末压（LVEDP）、左心室发展压（LVDP）、左心室内压上升/下降最大速率（±dp/dt max），以及LVESP、LVDP、+dp/dt max与平衡末差值占比。结果 IR模型组再灌注15、75 min灌流液中CK-MB和LDH水平均高于对照组［CK-MB：(234±51)U/L比（12±6）U/L，(203±63)U/L比（14±3）U/L；LDH：(63.9±9.4)U/L比（6.2±4.6）U/L，(52.1±9.5)U/L比（6.3±4.8）U/L］；PTSL、PTSM、PTSH组再灌注75 min灌流液CK-MB水平和再灌注15 min LDH水平均低于IR模型组，PTSL、PTSH组再灌注75 min LDH水平均低于IR模型组（均P＜0.05）。对照组不同时点灌流液心肌酶指标水平比较差异均无统计学意义（均P＞0.05）。与对照组比较，IR模型组再灌注15、75 min LVDP、+dp/dt max均降低，LVEDP、-dp/dt max以及LVESP、LVDP、+dp/dt max与平衡末差值占比均升高（均P＜0.05）。与IR模型组比较，PTSL组、PTSM组、PTSH组再灌注15 min LVEDP，PTSL组再灌注75 min LVEDP均降低,PTSM组再灌注75 min LVDP、+dp/dt max均升高，局部缺血30 min、再灌注75 min -dp/dt max均降低，PTSL组、PTSM组、PTSH组LVESP、LVDP、+dp/dt max与平衡末差值占比均显著降低（均P＜0.05）。PTSL组、PTSH组心率在平衡灌注20 min，PTSM组在平衡灌注20 min、局部缺血30 min和再灌注15、75 min均高于IR模型组（均P＜0.05）。结论 在大鼠离体心脏局部IR损伤模型中，三七三醇皂苷具有减少心肌酶的释放、减轻左心室收缩和舒张功能障碍的作用。

• Objective To establish a  model of local ischemia-reperfusion(IR) in Langendorff isolated-heart and to investigate the effect of panaxatriol saponins（PTS） on ischemia-reperfusion injury in isolated-rat heart.Methods Totally 40 healthy male Wistar rats were divided into the control group, the IR model group and low, medium and high dose PTS groups (PTSL group, PTSM group, PTSH group), with 8 rats in each group. In the control group, proximal branch of the left anterior descending coronary artery was threaded without ligaturing. K-H buffer was continuously reperfused for 105 min. In the IR model group, proximal branch of the left anterior descending coronary artery was threaded and ligatured for 30 min, and then the ligation was loosened. K-H buffer was reperfused for 75 min. In PTSL group, PTSM group and PTSH group, the proximal branch of the left anterior descending coronary artery was threaded and ligatured for 30 min, and K-H buffer respectively containing 5, 10 and 20 mg/L PTS were reperfused for 75 min.  The levels of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) were measured by collecting the perfusate of balanced perfusion for 20 min, local ischemia 30 min and reperfusion for 15 and 75 min in 5 groups. The cardiac hemodynamic parameters recorded by polysomnography including heart rate, left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), left ventricular development pressure (LVDP), maximum rate of left ventricular pressure rise/fall (±dp/dt max) and the ratios of LVESP, LVDP, +dp/dt max to final equilibrium difference value were compared among 5 groups at balanced perfusion for 20 min, focal ischemia for 30 min and reperfusion for 15 and 75 min. Results  At reperfusion for 15, 75 min，the levels of CK-MB and LDH in perfusate of the IR model group  were higher than those in the control group ［CK-MB:(234±51)U/L vs (12±6)U/L,(203±63)U/L vs (14±3)U/L; LDH:(63.9±9.4)U/L vs (6.2±4.6)U/L, (52.1±9.5)U/L vs (6.3±4.8)U/L］(all P<0.05). The levels of CK-MB at the reperfusion for 75 min and LDH at the reperfusion for 15 min in perfusate of PTSL, PTSM and PTSH groups were lower than those in the IR model group, and the levels of LDH at reperfusion for 75 min in PTSL and PTSH groups were lower than those in the IR model group(all P＜0.05). There were no significant differences in myocardial enzyme levels at different time points in the control group(all P＞0.05). Compared with the control group, the LVDP and +dp/dt max at reperfusion for 15, 75  min in the IR model group were decreased, and LVEDP, -dp/dt max and  the ratios of  LVESP, LVDP, +dp/dt max to final equilibrium difference value in the IR model group were increased(all P＜0.05). LVEDP at reperfusion for 15 min in PTSL group, and LVEDP at reperfusion for 75 min in PTSM group were lower than those in IR model group; LVDP, +dp/dt max at reperfusion for 75 min in PTSM group were lower than those in IR model group; -dp/dt max at local ischemia for 30 min and reperfusion for 75 min in PTSM group were higher than those in IR model group; the ratios of LVESP, LVDP, +dp/dt max to final equilibrium difference value in PTSL, PTSM and PTSH groups were higher than those in IR model group (all P<0.05). The heart rate at balanced perfusion for 20 min in PTSL group and PTSH group,  and that at balanced perfusion for 20 min, local ischemia for 30 min and reperfusion for 15,  75 min of PTSM group were higher than those in IR model group (all P<0.05). Conclusion In the model of isolated-heart local IR injury of rats, PTS can reduce the release of myocardial enzymes and relieve left ventricular systolic and diastolic dysfunction.