| BackgroundsMethamphetamine（MA）is a potent central nervous system stimulant and is the main component of methamphetamine.MA repeatedly ingested is extremely susceptible to drug addiction,which is a chronic recurrent encephalopathy related to reward effects and learning memory.The mechanisms of neurotoxicity have been studied clearly.Most studies on the cardiotoxicity of MA addiction are limited to myocardial infarction,heart failure,arrhythmia,etc.There are few studies on the way MA is regulated to cause myocardial damage,and few studies on the mechanism of cardiovascular damage after MA addiction.ObjectiveTo investigate the changes in cardiac function,histological changes in the left ventricle and changes in the expression of norepinephrine transporter（NET）and dopamine transporter（DAT）in the left ventricle of rats after addiction to MA,in order to further investigate the mechanism of the toxic effects of clinical MA addiction on the heart.This study will provide a theoretical basis for further research on the mechanism of the toxic effects of clinical MA addiction on the heart.Methods20 8-week-old SPF-grade adult male SD rats were divided into two groups according to the complete randomization method: MA group and control group,10 rats in each group,and 3 rats in each group were selected at complete random as the pre-modeling baseline values,and the methamphetamine addiction model was established using the conditioned place preference（CPP）experiment.MA was dissolved in 0.9% saline to make MA saline solution at a concentration of 5 mg/m L;rats in the MA group were injected intraperitoneally with methamphetamine hydrochloride solution at a concentration of 5 mg/m L according to the body weight of each rat on Day 5,7,9,11,13,15 and 17,respectively.Day 6,8,10,12,14,16,18 MA group and control rats were injected intraperitoneally with 1 m L/kg saline.On day 1 and day 19,echocardiography was performed in MA and control rats,respectively.After echocardiography on day 19,200 m L of saline and 200 m L of 4% paraformaldehyde solution were used for cardiac perfusion,after which the material was fixed in 4 % paraformaldehyde solution for 24 h.The changes in cardiac function and morphological changes of the left ventricle were observed in both groups by HE staining.HE staining was performed to observe the changes of cardiac function and left ventricular morphology in both groups.Results1.The results of the conditioned place preference test showed that methamphetamine addiction caused a significantly longer residence time（404.478 ±87.512）s in the white chamber during the test period after drug administration in rats compared to the control group with a residence time of（183.570 ± 74.355）s in the white chamber during the test period（P < 0.05）,suggesting successful modeling of the MA addiction model.2.Echocardiographic results showed that the left ventricular ejection fraction decreased in the MA group rats after administration of the drug compared to the control group.3.HE staining showed that the arrangement of myocardial cells in the left ventricle of MA rats was disturbed,and myocardial hemorrhage,ripple-like changes in myocardial cells,and inflammatory cell aggregation in the myocardium were seen,suggesting that MA can cause myocardial cell damage in the left ventricle of rats,and pathological changes such as necrosis and degeneration occurred.4.Immunohistochemical results showed a decrease in the positive products of NET and DAT immunoreactivity in the left ventricle of rats in the MA group（P< 0.05）,indicating that MA exerted a toxic effect on the cardiovascular.Conclusions1.MA addiction causes hypocardial function in rats,and MA addiction causes pathological changes in rat left ventricular cardiomyocytes.2.The reduced expression levels of NET and DAT in the left ventricle of rats eventually led to pathological changes such as myocardial injury.It is suggested that the abnormal NET and DAT transport may be one of the mechanisms of myocardial injury in the left ventricle of MA-addicted rats. |
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