甲基苯丙胺对大鼠心肌损伤作用的毒性影响机制初探

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目的研究慢性甲基苯丙胺(METH)中毒大鼠心肌细胞组织病理学的变化及慢性METH给药对心肌细胞L型钙通道(LTCCs)的毒性损伤作用。方法建立METH慢性大鼠中毒模型,对大鼠心脏系数的改变进行统计分析;对心肌组织进行HE、PTAH和HBFP染色,光学显微镜下观察心肌组织形态学改变;对心肌进行LTCCsα1c、β2亚基免疫组化染色,计算机图像分析系统半定量分析染色光密度,比较各组大鼠心肌免疫组化染色差异。结果慢性METH中毒模型大鼠心脏系数增高,与对照组比较差异有统计学意义(t=7.721,P<0.01);慢性METH毒性损伤表现为大鼠心肌细胞程度不一的嗜酸性增强、收缩带坏死、肌溶灶形成、波浪样改变,心肌间质出血及少量炎性细胞浸润;慢性METH中毒模型大鼠的心肌LTCCsα1c、β2亚基阳性染色,与对照组比较,差异有统计学意义(P均<0.01)。结论慢性METH中毒模型大鼠心脏肥大、心肌缺血缺氧性形态学改变,心肌LTCCsα1c亚基和β2亚基在心肌细胞的表达水平高。 Objective To investigate the changes of histopathology in cardiomyocytes induced by chronic methamphetamine (METH) in rats and the toxic effects of chronic METH administration on L-type calcium channels (LTCCs) in cardiomyocytes. Methods To establish the model of chronic poisoning rats with METH and to analyze the change of rat heart coefficient. HE, PTAH and HBFP staining were performed on myocardial tissue. The morphological changes of myocardium were observed under light microscope. The expressions of LTCCs α1c and β2 subunits Histochemical staining, computer image analysis system semi-quantitative analysis of optical density, myocardial tissue immunohistochemical differences between groups were compared. Results Compared with the control group, the cardiac coefficient of rats with chronic METH poisoning increased significantly (t = 7.721, P <0.01). The chronic METH toxicity injury manifested as eosinophilic increase of varying degrees of myocardial cells in rats, Necrosis, formation of kyphosis, wave-like changes, myocardial interstitial hemorrhage and a small amount of inflammatory cell infiltration. The positive staining of LTCCs α1c and β2 subunits in chronic METH poisoning model rats was statistically significant compared with the control group (P All <0.01). Conclusions The morphological changes of cardiac hypertrophy, myocardial ischemia and hypoxia in chronic METH poisoning model rats were observed. The expression of myocardial LTCCs α1c subunit and β2 subunit in cardiomyocytes was high.
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