Investigate Of The Toxic Effects Of Heroin On Rat Embryonic Tissue

Objective:In order to further explore the genetic toxicity of heroin and its effects on embryonic tissue cells,Wistar rats were used as experimental subjects.Heroin was injected at different concentrations during the development of rat embryos to observe the development of fetal rats,and to analyze and analyze the effects of heroin on embryonic tissues,organs and The influence of the development of the nervous system,exploring the toxic effects of heroin during the development of the embryonic nervous system,has aroused people’s attention to the health hazards of heroin to women and offspring,and provided theoretical basis for heroin treatment and rehabilitation,prevention of drug abuse and detoxification.Methods:Seventy-two male and 144 female SPF Wistar rats with healthy sexual maturity were selected and weighed（200±10）g.They were reared in the SPF laboratory for7 days and reared according to female:male=2:1 cages.The vaginal sperm smear test was performed the next morning after the mating mating,and the sperm was detected as mating,and the day of conception was 0 days of pregnancy（denoted as E0）.After mating and pregnancy,female wistar pregnant rats were randomly divided into 4 groups according to the time of pregnancy:heroin low-dose group（15 mg/kg body weight）:heroin was injected intramuscularly on days 7-15 of pregnancy;heroin medium-dose group（30mg/kg body weight）:Heroin was injected intramuscularly on days 7-15 of pregnancy;heroin high-dose group（60 mg/kg body weight）:heroin was injected intramuscularly on days 7-15 of pregnancy;experimental control group:saline was injected intramuscularly on days 7-15 of pregnancy.Establishment of a pregnant rat model of drug addiction.On the 20th day of pregnancy,anesthetize pregnant mice with ether inhalation,open the thoracic and abdominal cavity,and observe live,still and absorbed fetuses;observe the effects of heroin on the development of embryonic tissues and organs;Immunohistochemistry（Bax,c-Fos,GABA）was used to explore the toxic effects of heroin during embryonic neurological development;q RT-PCR was used to examine the inhibitory effects of overexpressed mi R-129-5p on rat germ cells.Results:1. Heroin can affect the appetite of rats,causing a tendency for rats to lose weight and,at the same time,causing a lack of nutrients in the fetal rats in utero,causing the developing fetal rats to become physically stunted and lose weight.Weight gain was significantly lower in the heroin group than in the control group,especially in the 60mg·kg^-1dose-group with a stepwise decrease in body weight in pregnant rats after day 5 of heroin injection,which was cross-checked with early stillbirths after bedtime and dose related.2. The embryos were observed on day 20 at different doses of heroin administered to rats during embryonic development:Compared with the control group,the survival rate of rats in the 15mg·kg^-1dose-group was not significantly different,suggesting that this dose had no significant effect on embryonic development;the survival rate of embryos in the 30mg·kg^-1dose-group and the 60mg·kg^-1dose-group decreased in a stepped manner with increasing dose and the malformation rate increased in a stepped manner.3. Compared with the control group,the 15mg·kg^-1dose-group recombinant fetuses had more malformations on the body surface and limbs,and no obvious malformations of brain structure and bone were seen;in the 30mg·kg^-1dose-group,the type and number of malformations on the body surface and limbs increased,the midbrain conduit and left and right ventricles were widened,the cerebral hemispheres were underdeveloped,the ribs were incompletely ossified and distorted,the vertebrae were incomplete and the metacarpals were not ossified;in the 60mg·kg^-1dose-group,not only the type and number of malformations on the body surface and limbs increased,but also abdominal cleft,scoliosis,no ear,eyeball protrusion,facial cleft,cleft jaw,occipital cleft brain expansion,etc.The degree of brain tissue and bone malformations increased significantly.4. Compared with the control group,the heroin group not only induced the expression of Bax and c-Fos in the brain cortex of embryonic rats,stimulated the increase and acceleration of apoptosis and increased the toxic effects during organ development,but also showed a positive dose correlation;the number of GABA-positive neurons in the hippocampal DG area of embryonic rats was significantly lower in the heroin group than in the control group,and showed a negative dose correlation.5. Heroin can be involved in the development of fibroblast damage in rat embryos by regulating mi R-129-5p overexpression.Conclusion:Compared with the control group,heroin had different inhibitory effects on body weight of pregnant rats;it had significant toxic effects on embryonic rats and showed positive dose correlation;heroin could induce the expression of Bax and c-Fos in the cerebral cortex of embryonic rats,stimulate the increase and acceleration of apoptosis and increase the toxic effects during organ development,and these effects showed positive dose correlation;heroin could inhibit the number of GABA-positive neurons in the hippocampal DG area of embryonic rats and showed negative heroin dose correlation;heroin could participate in the process of fibroblast damage in rats by regulating miR-129-5p overexpression.