蒺藜皂苷对大鼠心肌缺血再灌注损伤的保护作用
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摘要
蒺藜皂苷是从蒺藜科植物蒺藜地上全草中提取的有效组分之一。药理学研究表明,蒺藜皂苷具有明显的降低血压、保护脑缺血、抑制血小板凝聚等心血管系统方面的作用。此外,在抗衰老、增强机体免疫力等方面具有广泛的药理价值。为探讨蒺藜皂苷对心肌缺血再灌注损伤的治疗作用及其机制,本文进行了如下研究:
采用结扎左冠状动脉前降支,对大鼠心脏进行40min缺血和120min再灌注,建立大鼠心肌缺血再灌注损伤模型。蒺藜皂苷对心肌缺血/再灌注损伤大鼠血清AST、CK和LDH活性的影响。与假手术组比较,模型组大鼠血清中AST、CK和LDH含量显著升高,具有显著性差异(P＜0.001);与模型组比较,蒺藜皂苷高、中、低剂量组、阳性对照药血塞通组能明显降低大鼠血清中AST、CK和LDH的含量,具有显著性差异(P＜0.05,P＜0.01)。
蒺藜皂苷对心肌缺血/再灌注损伤大鼠血清中SOD活性和MDA、NO含量的影响。与假手术组比较,模型组大鼠血清中NO、SOD活性降低,MDA含量明显增加,具有显著性差异(P＜0.001);蒺藜皂苷高、中剂量组、阳性对照药血塞通组可明显升高大鼠血清中SOD、NO活性,降低MDA水平,与模型组比较具有显著性差异(P＜0.05,P＜0.01)。
蒺藜皂苷对心肌缺血再灌注损伤大鼠心肌组织病理形态学改变的影响。光镜下假手术组心肌纤维排列整齐,心肌间质无炎性细胞浸润;模型组心肌纤维肿胀,排列紊乱,心肌间质出现大量炎细胞浸润,甚至可见局灶性坏死区;GSTT各剂量组心肌细胞核大小均一,心肌纤维轻度肿胀,偶见成纤维细胞及炎细胞浸润;阳性对照药血塞通组镜下和GSTT剂量组相似。
通过上述实验,初步证实蒺藜皂苷对心肌缺血-再灌注损伤具有治疗作用,其机制为:减少自由基的生成,提高机体清除自由基能力,抗脂质过氧化反应,抑制因自由基损伤而导致的细胞死亡。
The most effective method of limiting acute myocardial ischemia necrosis is reperfusion. The effect of reperfusion itself may be associated with polymophonuclear leucocyte(PMN) accumulation,a burst of oxygen free radical production.,activation of inflammation and calcium overload,which may result in paradoxical cardiomyocyte dysfunction a phenomenon termed reperfusion injury.Studies on the new agents used to treat myocardial ischemia reperfusion are still a pivotal issue.
In the situation of myocardial ischemia,SOD decreases and LPO increases with its toxic output-MDA increasing relatively.MDA is a kind of toxic substance,which can overoxidate cell membrane.
Tribulus terrestris is also called Bai Jili and Ci Jili.It refers to the dry,ripe fruit of the plant caltrop.Its main chemical ingredients are saponins,ketone,alkaloid.The gross saponins of Tribulus terrestris(GSTT)was one of the effective group ingredients which was extracted from the whole plant of caltrop.It is a mixture of over 10 kinds of saponins,mainly steroid saponins.It is a powder and dissolvable in water.Domestic research materials showed that GSTT had the effect of lowering blood pressure and stimulating anti-hypoxia,sheeting blood vessels,lowering cholesterol,inhibiting fat deposition on arteries,myocardium and liver.
Our study discussed the therapeutic mechanism of GSTT through setting up myocardial ischemia-reperfusion model in rats In this project,we take the molecular technology to explore the mechanism to its protective effects.We made ischemia reperfusion model in rats to study the effects of GSTT on cadiocyte morphology changes and detect the activity of SOD、MDA、NO、AST、LDH、CK in rats serum.As the result of that the changes of cadiocyte morphology was serious edema and cytoplasm was stained slightly and nuclei were contracted and strained deeply after reperfusion.GSTT(30mg·kg~(-1)、15mg·kg~(-1))reduced cellular edema, maintained the cadiocyte morphology.After myocardial ischemia-reperfusion,content of AST、LDH、CK and MDA increased but SOD and NO depressed(P＜0.05).GSTT group (30mg·kg~(-1)、15mg·kg~(-1)) could decrease the content of AST、LDH、CK、MDA and increase SOD、NO(P＜0.05).GSTT can lessen the myocardial ischemia-reperfusion injury.
All these findings suggest that GSTT has the therapeutic potential against myocardial ischemia-reperfusion injury in rats.Therapeutics effects may be related to inhibition of lipid oxidation,protection modulation of endogenous antioxidant enzyme activitie.
采用结扎左冠状动脉前降支,对大鼠心脏进行40min缺血和120min再灌注,建立大鼠心肌缺血再灌注损伤模型。蒺藜皂苷对心肌缺血/再灌注损伤大鼠血清AST、CK和LDH活性的影响。与假手术组比较,模型组大鼠血清中AST、CK和LDH含量显著升高,具有显著性差异(P＜0.001);与模型组比较,蒺藜皂苷高、中、低剂量组、阳性对照药血塞通组能明显降低大鼠血清中AST、CK和LDH的含量,具有显著性差异(P＜0.05,P＜0.01)。
蒺藜皂苷对心肌缺血/再灌注损伤大鼠血清中SOD活性和MDA、NO含量的影响。与假手术组比较,模型组大鼠血清中NO、SOD活性降低,MDA含量明显增加,具有显著性差异(P＜0.001);蒺藜皂苷高、中剂量组、阳性对照药血塞通组可明显升高大鼠血清中SOD、NO活性,降低MDA水平,与模型组比较具有显著性差异(P＜0.05,P＜0.01)。
蒺藜皂苷对心肌缺血再灌注损伤大鼠心肌组织病理形态学改变的影响。光镜下假手术组心肌纤维排列整齐,心肌间质无炎性细胞浸润;模型组心肌纤维肿胀,排列紊乱,心肌间质出现大量炎细胞浸润,甚至可见局灶性坏死区;GSTT各剂量组心肌细胞核大小均一,心肌纤维轻度肿胀,偶见成纤维细胞及炎细胞浸润;阳性对照药血塞通组镜下和GSTT剂量组相似。
通过上述实验,初步证实蒺藜皂苷对心肌缺血-再灌注损伤具有治疗作用,其机制为:减少自由基的生成,提高机体清除自由基能力,抗脂质过氧化反应,抑制因自由基损伤而导致的细胞死亡。
The most effective method of limiting acute myocardial ischemia necrosis is reperfusion. The effect of reperfusion itself may be associated with polymophonuclear leucocyte(PMN) accumulation,a burst of oxygen free radical production.,activation of inflammation and calcium overload,which may result in paradoxical cardiomyocyte dysfunction a phenomenon termed reperfusion injury.Studies on the new agents used to treat myocardial ischemia reperfusion are still a pivotal issue.
In the situation of myocardial ischemia,SOD decreases and LPO increases with its toxic output-MDA increasing relatively.MDA is a kind of toxic substance,which can overoxidate cell membrane.
Tribulus terrestris is also called Bai Jili and Ci Jili.It refers to the dry,ripe fruit of the plant caltrop.Its main chemical ingredients are saponins,ketone,alkaloid.The gross saponins of Tribulus terrestris(GSTT)was one of the effective group ingredients which was extracted from the whole plant of caltrop.It is a mixture of over 10 kinds of saponins,mainly steroid saponins.It is a powder and dissolvable in water.Domestic research materials showed that GSTT had the effect of lowering blood pressure and stimulating anti-hypoxia,sheeting blood vessels,lowering cholesterol,inhibiting fat deposition on arteries,myocardium and liver.
Our study discussed the therapeutic mechanism of GSTT through setting up myocardial ischemia-reperfusion model in rats In this project,we take the molecular technology to explore the mechanism to its protective effects.We made ischemia reperfusion model in rats to study the effects of GSTT on cadiocyte morphology changes and detect the activity of SOD、MDA、NO、AST、LDH、CK in rats serum.As the result of that the changes of cadiocyte morphology was serious edema and cytoplasm was stained slightly and nuclei were contracted and strained deeply after reperfusion.GSTT(30mg·kg~(-1)、15mg·kg~(-1))reduced cellular edema, maintained the cadiocyte morphology.After myocardial ischemia-reperfusion,content of AST、LDH、CK and MDA increased but SOD and NO depressed(P＜0.05).GSTT group (30mg·kg~(-1)、15mg·kg~(-1)) could decrease the content of AST、LDH、CK、MDA and increase SOD、NO(P＜0.05).GSTT can lessen the myocardial ischemia-reperfusion injury.
All these findings suggest that GSTT has the therapeutic potential against myocardial ischemia-reperfusion injury in rats.Therapeutics effects may be related to inhibition of lipid oxidation,protection modulation of endogenous antioxidant enzyme activitie.
引文
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[2]Heyndrickx GR, Millard RW, McRitchie RJ, et al. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs[J]. J Clin Invest 1975, 56(4):978-85.
[3]Foster DB,Van Eyk JE. In search of the proteins that cause myocardial stunning[J].Circ Res, 1999, 85(5): 470-472
[4]Moens AL, Claeys MJ, Timmermans JP, Vrints CJ. Myocardial ischemia/ reperfusion-injury, a clinical view on a complex pathophysiological process[J]. Int J Cardiol. 2005 Apr 20,100(2):179-90.
[5]Carmeliet E. Cardiac Ionic currents and acute ischemia: from channels to arrhythmias [J]. Physiol Rev. 1999, 79(3):917-1017.
[6]Harris AS, Otero H, Bocage AJ. The induction of arrhythmias by sympathetic activity before and after occlusion of a coronary artery in the canine heart[J]. J Electrocardiol. I 971,4(1):34-43.
[7]Morishima I, Sone T, Okumura K, et al. Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with Percutaneous transluminal coronary angioplasty for first acute myocardial infarction[J]. J Am Coll Cardiol.2000, 36(4): 1202-1209
[8]Taniyama Y, Ito H, Iwakura K, et al. Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction[J]. J Am Coll Cardiol, 1997, 30(5): 1193-1199
[9]Shimizu S, Eguchi Y, Kamiike W, Itoh Y, Hasegawa J, Yamabe K, Otsuki Y, Matsuda H, Tsujimoto Y. Induction of apoptosis as well as necrosis by hypoxia and predominant prevention of apoptosis by Bcl-2 and Bcl-XL[J].Cancer Res. 1996, 56:2161-2166.
[10]Clerk A, Cole SM, Cullingford TE, Harrison JGS Jormakka M, Valks DM.Regulation of cardiac myocyte cell death[J]. Pharmacol Ther. 2003 Mar, 97(3):223-61.
[11]Ha HC, Snyder SH: Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion[J].Proc Natl Acad Sci USA 1999,96:13978-13982.
[12]Krijnen PA,Nijmeijer R,Meijer CJ,Visser CA,Hack CE,Niessen HW.Apoptosis in myocardial ischaemia and infarction[J].J Clin Pathol.2002,55:801-811.
[13]Chakrabarti S,Hoque AN,Karmazyn M.A rapid ischemia-induced apoptosis in isolated rat hearts and its attenuation by the sodium-hydrogen exchange inhibitor HOE 642(cariporide)[J].J Mol Cell Cardiol,1997,29(11):3169-3174
[14]Bolli R,Marban E.Molecular and cellular mechanisms of myocardial stunning [J].Physiol Rev,1999,79(2):609-634
[15]Taegtmeyer H,Goodwin GW,Doenst T,et al.Substrate metabolism as a determinant for postischemic functional recovery of the heart[J].Am J Cardiol,1997,80(3A):3A-10A.
[16]朱甫样,马丽英,王孝铭,等.局部肾素一血管紧张素系统在心肌细胞氧反常中的作用[J].中国病理生理杂志,1997,13:126-128
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