延胡索总生物碱对异丙肾上腺素诱导的心肌梗死大鼠的心肌保护作用

Protective effects of total fumaric alkaloids on myocardium of rats with isoproterenol-induced myocardial infarction

目的探讨延胡索总生物碱对异丙肾上腺素(ISO)诱导的心肌梗死大鼠损伤心肌的保护作用。方法 SD大鼠60只,随机分为四组(每组15只),A组大鼠采用ISO诱导心肌梗死,并使用1.0 mg/kg延胡索总生物碱预处理。B组大鼠采用ISO诱导心肌梗死,并使用2.0 mg/kg延胡索总生物碱预处理。C组大鼠仅用ISO诱导心肌梗死。对照组大鼠不接受ISO和延胡索总生物碱处理。检测各组大鼠血流动力学参数和左心室功能参数。采集各组大鼠血浆及心肌组织标本,检测心肌组织中的氧化应激指标变化及凋亡相关蛋白的表达变化。检测血浆标本中心肌损伤标志物的水平。光学显微镜下观察各组大鼠心肌损伤情况。结果与C组大鼠相比,延胡索总生物碱预处理可以有效抑制ISO引起的收缩动脉压、舒张动脉压及平均动脉压的降低,同时能够缓解ISO引起的心率降低(P均<0.05)。A组和B组大鼠的左心室最大收缩压变化速率及左心室最大舒张压变化速率均高于C组,左心室舒张末压均低于C组,上述差异具有统计学意义(P均<0.05)。与C组大鼠相比,A组和B组大鼠的丙二醛水平降低,谷胱甘肽、超氧化物歧化酶、过氧化氢酶及谷胱甘肽过氧化物酶的水平有所回升(P均<0.05)。A组和B组大鼠血浆中的心肌损伤指标肌酸激酶-MB和乳酸脱氢酶水平明显低于C组(P均<0.05)。光镜下对各组心肌组织的形态学检查可见,A组和B组大鼠心肌组织的坏死、炎性细胞浸润及心肌细胞水肿情况轻于C组。Western blot分析可见,A组和B组大鼠心肌组织的抗凋亡蛋白Bcl-2表达量高于C组,而促凋亡蛋白Bax低于C组。结论延胡索总生物碱可减轻ISO诱导心肌梗死大鼠的氧化应激,稳定血流动力学参数,保护心功能,减轻心肌损伤和凋亡。

Objective To investigate the protective effects of total fumaric alkaloids on myocardium of rats with isoproterenol（ ISO）-induced myocardial infarction. Methods Sixty SD rats were randomly divided into four groups： group A,B,C and control group（ n = 15 each）. The myocardial infarction rat model was established by subcutaneous injection of ISO in group A,B and C,and the pretreatments of 1. 0 mg / kg and 2. 0 mg / kg of total fumaric alkaloids were respectively given before modeling in group A and B. Nether ISO nor total fumaric alkaloids were given in control group. The hemodynamic parameters and left ventricular function parameters were observed. The plasma and myocardial tissue samples were collected to respectively detect the plasma myocardial injury markers,the oxidative stress markers of myocardial tissue and the expressions of apoptosis-associated proteins in the myocardial tissues. The histopathology changes of myocardial damage were observed under the optical microscope. Results Compared with group C,the pretreatments of total fumaric alkaloids can effectively inhibit the deacreases of arterial systolic pressure（ ASP）,arterial diastolic pressure（ ADP）,mean arterial pressure（ MAP） and heart rate（ HR） induced by ISO（ all P〈0. 05）. Compared with group C,the change rates of left ventricular maximum systolic pressure（ ＋ LVd P / dtmax） and maximum diastolic pressure（-LVd P/dtmax） increased significantly,and left ventricular end-diastolic pressures（ LVEDP） decreased significantly in groups A and B（ all P〈0. 05）. Comparedwith group C,the malondialdehyde（ MDA） level decreased significantly; the levels of glutathione（ GSH）,superoxide dismutase（ SOD）,catalase（ CAT） and glutathione peroxidase（ GSHPx） increased significantly; plasma myocardial injury indexes including creatine kinase（ CK）-MB and lactic dehydrogenase（ LDH） decreased in groups A and B（ all P〈0. 05）.The finding of morphological examination under optical microscope showed that the myocardial tissue necrosis,inflammatory cell infiltration and myocardial cellular edema in group A and B were all lighter than that in group C. Western blot analysis showed that the Bcl-2（ anti-apoptotic protein） expressions increased,and Bax（ apoptotic protein） expressions decreased in group A and B compared with group C. Conclusions Total fumaric alkaloids could alleviate the oxidative stress of myocardial tissues,maintain hemodynamic stabilization,protect heart functions and lighten myocardial injury and apoptosis in rats with ISO-induced myocardial infarction.