The Changes Of NO,MDA,SOD And Blood-Brain Barrier Permeability Of Heroin-Addicted Rats

Objective: To explore the mechanism of heroin addiction-induced brain injury by observing the changes of nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and the blood-brain barrier(BBB) permeability in animal experiments.Methods:①60 adult female Sprague-Dawley (SD) rats were divided into two groups: heroin model group and control group by the method of random number. To establish the animal model of heroin addicted, the rats in heroin model group were given subcutaneous injection of heroin by incremental method. The rats in control group were injected normal saline without heroin by the same way.②After the establishment of animal model, the rats were given the intraperitoneal injection of naloxone, heroin addiction strength was judged by the Maldonado addiction withdrawal symptoms score criteria.③The ability of learning and space memory was tested by Morris water maze.④After the test of water mase, 10 rats were randomly selected in each group to decapitate the brain and the brain were separated into frontal cortex, hippocampus, diencephalon, cerebellum and brain stem, then the changes of NO, MDA, and SOD were measured by chemical colorimetric method in each brain parts.⑤3 rats in each group were randomly selected to observe the microstructure changes of BBB structure by the transmission electron microscope;⑥7 rats in each group were randomly selected to anesthesia and give Evans blue (Evans blue, EB) tracer via the right femoral vein, then to observe EB leakage by the fluorescence microscopy;⑦10 rats in each group were randomly selected to anesthesia and give EB tracer via the right femoral vein, then to determine the contents EB of brain by the fluorescence spectrophotometer.Result:①The weight, spirit, fur color of rats in model group were worse than those in the control group.②The naloxone test of heroin addiction model rats was positive(p<0.01).③Compared with those rats in control group ,the escape latency of model group rats of heroin addiction became longer (P <0.05);the cross-platform number was decreased(P <0.05); the first time through platform became longer(P<0.05);the average swimming speed was not different between two groups(p>0.05).④Compared with those rats in the control group, the contents of NO in the frontal cortex, diencephalon and brain stem of model group were increased(p <0.05); the contents of NO was significantly increased in the hippocampus and cerebellum of brain (p <0.01); the contents of MDA were increased in the frontal cortex and diencephalon (p <0.05); the contents of MDA were significantly increased in the hippocampus, cerebellum and brain stem (p<0.01); the contents of SOD were decreased in the frontal cortex, diencephalon and cerebellum (p<0.05); the contents of SOD were significantly decreased in the hippocampus and brain stem (p<0.01).The contents of NO in the model group of heroin addicted were negatively correlated with MDA in the area of brain (p<0.05); the contents of NO were negatively correlated with SOD (p <0.01); the contents of MDA were negatively correlated with SOD (p<0.05);⑤A series of ultra structural changes of BBB permeability were increased compared with the rats in the control group under the Electron microscopy.⑥The number of EB fluorescent spots in heroin addiction model group were increased compared with the rats in the control group (p<0.05).⑦The contents of EB in heroin addiction model group was increased compared with the control group (p <0.05).Conclusion:①The incremental method of subcutaneous injection of heroin was available and effective.②The ability of learning and space memory of heroin addicted rats was decreased.③The contents of NO and MDA in heroin addiction rats were increased, while the contents of SOD were decreased.④The BBB permeability of heroin addicted rats brain was increased.⑤The heroin addicted rats were damaged by free radical in the brain tissues leaded to the increased permeability of BBB, then contributed to a series of changes of brain structure and function, which may be a pathological mechanism of the heroin addiction -induced brain injury.