怀牛膝总皂苷抗大鼠急性心肌缺血作用的研究
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摘要
目的通过怀牛膝总皂苷(ABS)对垂体后叶素(Pit)诱发的大鼠急性心肌缺血模型的研究,观察其对急性心肌缺血的疗效,阐明其抗心肌缺血的可能机制。
方法采用尾静脉注射Pit诱发大鼠急性心肌缺血模型,将SD大鼠随机分为6组,分别是正常对照组、模型组、复方丹参滴丸组(270mg/kg)、ABS高、中、低剂量组(1.25g/kg、1.0g/kg、0.75g/kg)。以△ST、心率、P-R间期作为大鼠心电图检测指标,观察模型的建立是否成功以及ABS对急性心肌缺血大鼠心电图的作用。测定大鼠血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)的含量,采用酶联免疫吸附法(ELISA)检测大鼠血清肌钙蛋白T(cTnT)、内皮素(ET)、血栓素B2(TXB2)、6-酮前列腺素(6-Keto-PGF1α)的含量。观察ABS对急性心肌缺血大鼠的药效作用及其对脂质过氧化反应、血管内皮功能以及血小板的作用情况。
结果由心电图可见模型组与正常组比较,缺血后各时间点△ST有显著性变化,心率显著性降低,P-R间期显著延长,血清CK、LDH、cTnT含量均有明显升高,表明造模成功；ABS高、中、低剂量组和复方丹参滴丸组与模型组比较,△ST、心率、P-R间期变化有明显改善,大鼠血清CK、LDH、cTnT含量显著降低(P<0.01,P<0.05),表明ABS具有良好的抗心肌缺血作用。与模型组比较,ABS高、中、低剂量组和复方丹参滴丸组SOD活力显著高于模型组,MDA含量显著低于模型组(P<0.01,P<0.05),表明ABS具有抗缺血后氧化损伤的作用；与模型组比较,ABS高、中、低剂量组均能够显著升高NO水平(P<0.01),降低ET含量(P<0.01,P<0.05),差异有统计学意义,表明ABS抗急性心肌缺血的作用可能通过调节NO和ET水平,保护血管内皮功能实现；与模型组比较,ABS高、中、低剂量组均能显著降低TXB2水平(P<0.01,P<0.05),ABS高、中剂量组能够显著升高6-Keto-PGF1α含量(P<0.05),差异有统计学意义,提示ABS抗Pit所致的大鼠急性心肌缺血可能是通过调节PGI2/TXA2失衡,抑制血小板聚集,对心肌缺血起到保护作用。
结论
1.采用大鼠尾静脉注射Pit后,心电图可见△ST显著变化,心率显著减慢,P-R间期显著延长,表明该急性心肌缺血模型比较成功。
2.怀牛膝总皂苷能够显著改善缺血后心电图的变化,减少心肌酶与cTnT的释放,表明其对急性心肌缺血损伤具有良好的保护作用。
3.怀牛膝总皂苷能够使SOD活力显著上升,降低MDA的含量,升高NO含量,提示其抗急性心肌缺血可能通过抑制脂质过氧化反应,减轻氧自由基对细胞的损伤实现。
4.怀牛膝总皂苷能够降低大鼠ET水平,升高NO水平,提示其抗急性心肌缺血可能通过扩张血管,保护血管内皮舒缩功能实现。
5.怀牛膝总皂苷能够显著降低TXB2水平,升高6-Keto-PGF1a水平,提示怀牛膝总皂苷能够通过平衡二者比值,改善心脏血管功能,抑制血小板聚集与血栓的形成。
Objective:To observe the effect and the mechanism of ABS on acute my-ocardial isehemia rat.
Method:To divide the 72 rats into control group, model group, low dosage gr ou p (0. 75g/kg), middle dosage group(1.0g/kg), high dosage group(1.25g/kg), FufangDansh-enDiwan group. With the way of venous injection of pituitrin below the rats'tail, to establish the acute myocardial ischemia. To observe the change on the electrocardi-ogram and CK,LDH,SOD,MDA to study the success of model and the effect of ABS on the acute myocardial ischemia. And to observe the change on the content of cTnT,ET,NO, TXB2 and 6-Keto-PGF1αto study the efficacy and mechanism of ABS.
Result:Compared with nomal group,model group can definitely affect the electrocar-diogram with the changing of△ST,HR and P-R interphase and increase the CK,LDH and cTnT.Compared with model group,ABS high-dose group,middle-dose group low-dose group and CDDP group can obviously affect the increasing of△ST and P-R interphase and the decreasing of HR.And the amount of LDH,CK and cTnT of ABS group and CDDP group was lower than model group(P<0.01,P<0.05).These results suggested that The ABS is capable of improving the effect caused by the myocardial ischemia on rats after experiment of pituitr.Compared with model group,ABS high-dose group,middle-dose group low-dose group and CDDP group SOD contents were more than model group,and the MDA contents were obviously lower than model group(P<0.01,P<0.05),indicated that the ABS can suppressed the drop of total anti-oxidative capacity.Compared with model group,ABS high-dose group,middle-dose group and lower-dose group NO contents were more than model group(P<0.01),and ET contents were lower than model group(P<0.01,P<0.05),indicated that ABS had a certain effect on vascular endothelial cells.Compared with model group,ABS high-dose group,middle-dose group and low-dose group TXB2 contents were lower than model group(P<0.01,P<0.05),and ABS high-dose group and middle-dose group 6-Keto-PGF1αa contents were more than model group(P<0.05),indicate than it can increase the ratio of PGI2/TXA2 in the myocardial ischemia on rats.
Conclusion:
1. With the way of venous injection of pituitrin below the rats'tail, model group can definitely affect the electrocardiogram with the changing of△ST,HR and P-R interp-hase,indicated that the model is successful.
2.The results indicated that ABS is capable of improving the effect caused by the myocardial ischemia on rats after experiment of pituitr.And the ABS could improve the electrocardiogram,decrease the release of enzyme and cTnT of myocardial.
3.The ABS could decrease thecontents of MDA and increase the contents of SOD.It indicated that ABS has function on anti-lipid peroxidation.
4.The ABS could decrease the contents of ET and increase the contents of NO.Tt indicated that ABS has effect on dilating vessels and protecting endothedial.
5.The ABS could decrease the contents of TXB2 and increase the contents of 6-Keto-PGF1α.It suggested that ABS has important action on function of vessels,and it also inhibit platelet aggregation and thrombus formation.
方法采用尾静脉注射Pit诱发大鼠急性心肌缺血模型,将SD大鼠随机分为6组,分别是正常对照组、模型组、复方丹参滴丸组(270mg/kg)、ABS高、中、低剂量组(1.25g/kg、1.0g/kg、0.75g/kg)。以△ST、心率、P-R间期作为大鼠心电图检测指标,观察模型的建立是否成功以及ABS对急性心肌缺血大鼠心电图的作用。测定大鼠血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)的含量,采用酶联免疫吸附法(ELISA)检测大鼠血清肌钙蛋白T(cTnT)、内皮素(ET)、血栓素B2(TXB2)、6-酮前列腺素(6-Keto-PGF1α)的含量。观察ABS对急性心肌缺血大鼠的药效作用及其对脂质过氧化反应、血管内皮功能以及血小板的作用情况。
结果由心电图可见模型组与正常组比较,缺血后各时间点△ST有显著性变化,心率显著性降低,P-R间期显著延长,血清CK、LDH、cTnT含量均有明显升高,表明造模成功；ABS高、中、低剂量组和复方丹参滴丸组与模型组比较,△ST、心率、P-R间期变化有明显改善,大鼠血清CK、LDH、cTnT含量显著降低(P<0.01,P<0.05),表明ABS具有良好的抗心肌缺血作用。与模型组比较,ABS高、中、低剂量组和复方丹参滴丸组SOD活力显著高于模型组,MDA含量显著低于模型组(P<0.01,P<0.05),表明ABS具有抗缺血后氧化损伤的作用；与模型组比较,ABS高、中、低剂量组均能够显著升高NO水平(P<0.01),降低ET含量(P<0.01,P<0.05),差异有统计学意义,表明ABS抗急性心肌缺血的作用可能通过调节NO和ET水平,保护血管内皮功能实现；与模型组比较,ABS高、中、低剂量组均能显著降低TXB2水平(P<0.01,P<0.05),ABS高、中剂量组能够显著升高6-Keto-PGF1α含量(P<0.05),差异有统计学意义,提示ABS抗Pit所致的大鼠急性心肌缺血可能是通过调节PGI2/TXA2失衡,抑制血小板聚集,对心肌缺血起到保护作用。
结论
1.采用大鼠尾静脉注射Pit后,心电图可见△ST显著变化,心率显著减慢,P-R间期显著延长,表明该急性心肌缺血模型比较成功。
2.怀牛膝总皂苷能够显著改善缺血后心电图的变化,减少心肌酶与cTnT的释放,表明其对急性心肌缺血损伤具有良好的保护作用。
3.怀牛膝总皂苷能够使SOD活力显著上升,降低MDA的含量,升高NO含量,提示其抗急性心肌缺血可能通过抑制脂质过氧化反应,减轻氧自由基对细胞的损伤实现。
4.怀牛膝总皂苷能够降低大鼠ET水平,升高NO水平,提示其抗急性心肌缺血可能通过扩张血管,保护血管内皮舒缩功能实现。
5.怀牛膝总皂苷能够显著降低TXB2水平,升高6-Keto-PGF1a水平,提示怀牛膝总皂苷能够通过平衡二者比值,改善心脏血管功能,抑制血小板聚集与血栓的形成。
Objective:To observe the effect and the mechanism of ABS on acute my-ocardial isehemia rat.
Method:To divide the 72 rats into control group, model group, low dosage gr ou p (0. 75g/kg), middle dosage group(1.0g/kg), high dosage group(1.25g/kg), FufangDansh-enDiwan group. With the way of venous injection of pituitrin below the rats'tail, to establish the acute myocardial ischemia. To observe the change on the electrocardi-ogram and CK,LDH,SOD,MDA to study the success of model and the effect of ABS on the acute myocardial ischemia. And to observe the change on the content of cTnT,ET,NO, TXB2 and 6-Keto-PGF1αto study the efficacy and mechanism of ABS.
Result:Compared with nomal group,model group can definitely affect the electrocar-diogram with the changing of△ST,HR and P-R interphase and increase the CK,LDH and cTnT.Compared with model group,ABS high-dose group,middle-dose group low-dose group and CDDP group can obviously affect the increasing of△ST and P-R interphase and the decreasing of HR.And the amount of LDH,CK and cTnT of ABS group and CDDP group was lower than model group(P<0.01,P<0.05).These results suggested that The ABS is capable of improving the effect caused by the myocardial ischemia on rats after experiment of pituitr.Compared with model group,ABS high-dose group,middle-dose group low-dose group and CDDP group SOD contents were more than model group,and the MDA contents were obviously lower than model group(P<0.01,P<0.05),indicated that the ABS can suppressed the drop of total anti-oxidative capacity.Compared with model group,ABS high-dose group,middle-dose group and lower-dose group NO contents were more than model group(P<0.01),and ET contents were lower than model group(P<0.01,P<0.05),indicated that ABS had a certain effect on vascular endothelial cells.Compared with model group,ABS high-dose group,middle-dose group and low-dose group TXB2 contents were lower than model group(P<0.01,P<0.05),and ABS high-dose group and middle-dose group 6-Keto-PGF1αa contents were more than model group(P<0.05),indicate than it can increase the ratio of PGI2/TXA2 in the myocardial ischemia on rats.
Conclusion:
1. With the way of venous injection of pituitrin below the rats'tail, model group can definitely affect the electrocardiogram with the changing of△ST,HR and P-R interp-hase,indicated that the model is successful.
2.The results indicated that ABS is capable of improving the effect caused by the myocardial ischemia on rats after experiment of pituitr.And the ABS could improve the electrocardiogram,decrease the release of enzyme and cTnT of myocardial.
3.The ABS could decrease thecontents of MDA and increase the contents of SOD.It indicated that ABS has function on anti-lipid peroxidation.
4.The ABS could decrease the contents of ET and increase the contents of NO.Tt indicated that ABS has effect on dilating vessels and protecting endothedial.
5.The ABS could decrease the contents of TXB2 and increase the contents of 6-Keto-PGF1α.It suggested that ABS has important action on function of vessels,and it also inhibit platelet aggregation and thrombus formation.
引文
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