ABSTRACT
BACKGROUND:Calcium channel abnormalities can damage myocardium. Heroin can directly affect calcium ion channel, and alter myocardial structure. OBJECTIVE:To study the changes of heroin-induced myocardial ultrastructure, L-type calcium channel current and action potential of myocardial cel s after rat cardiac arrhythmia. METHODS:Sprague-Dawley rats were randomly divided into control group and model group. In the model group, rats were administered heroin at initial dose of 5 mg/kg?d. The daily dose escalation method was used (increasing dose:2.5 mg/kg?d) to replicate rat models of heroin addiction. At 20 days, models of heroin addiction were successful y established. At 30 days after increasing the dose, rat models of heroin addiction-induced arrhythmias were further established. RESULTS AND CONCLUSION:Compared with the control group, the electron microscopy demonstrated that myocardial structure changes mainly presented nuclear membrane shrinkage, nuclear condensation, nuclei became smal , chromatin assembled into blocks, mitochondria disordered and disappeared, sarcomeres disordered, focal fracture, and unclear myofilament in rat models of heroin addiction. Electric current-voltage curve of myocardial cel L-type calcium channel current showed the increasing trends. The 90%repolarization action potential was significantly shortened. These data indicated that heroin can directly lead to the pathological change of myocardial structure. Calcium channel current change is one of the main reasons for myocardial injury.
ABSTRACT
Abstract BACKGROUND:Caspase-8 plays an important role in starting the process of cel apoptosis, and diacetylmorphine can induce neuronal apoptosis. The relationship between the apoptosis of cerebelar granule neurons cels induced by diacetylmorphine and caspase-8 has not been reported. OBJECTIVE:To investigate the effect of caspase-8 on diacetylmorphine-induced neuronal apoptosis. METHODS:Cerebelar granule neurons from Sprague-Dawley rats aged 7 days were culturedin vitro. At 7 days, the cels were cultured with different dosage of diacetylmorphine (10, 40, 80, 100, 120 mg/L) and SP600125 for 24 hours, and were divided into control group, 80 mg/L diacetylmorphine group, diacetylmorphine+SP600125 group. Cel morphology was observed by Hoechst 33258 fluorescent staining, and cel apoptosis rate was measured by flow cytometry. Immunofluorescence staining, RT-PCR and western blot assay were used to detect caspase-8 mRNA and protein expression. RESULTS AND CONCLUSION:(1) After different dosage of diacetylmorphine was used to induce neuronal apoptosis, dark blue translucent apoptotic bodies were found in apoptotic cels, appearing with nucleus condensation, cohesion and fracture, and the apoptosis rate presented an increasing trend with increasing of drug dosage (P < 0.05). (2) Compared with the control group, caspase-8 mRNA and protein expression was remarkable under the intervention of 80 mg/L diacetylmorphine(P < 0.05); caspase-8 mRNA expression exhibited an increasing trend with increasing dosage of diacetylmorphine (P < 0.05), while caspase-8 mRNA and protein expression in the diacetylmorphine+SP600125 group was significantly lower than that in the 80 mg/L diacetylmorphine group (P < 0.05). These findings indicate that caspase-8 is involved in the process of diacetylmorphine-induced neuronal apoptosis, and meanwhile, it is also an important candidate of pro-apoptotic factors in the c-jun N-terminal kinase signaling pathway.