Effects Of Methamphetamine On Endocrine Function Of Rhesus Macaques And Its Related Mechanisms

Objective:To explore the effect of methamphetamine on the endocrine function of rhesus macaques and its related mechanisms..By detecting rhesus macaques HPA,HPG and HPT axis related hormone levels,Histological changes of pathological specimens were observed.RT-PCR and western blot were used to detect the related factors of apoptosis in specimen(Bcl-2,BAX).animal model and the control group in the mRNA and protein expression level of the difference.To understand the differences in mRNA and protein levels in animal models and control groups.To provides a scientific experimental basis for the effect of methamphetamine on endocrine function and the related damage mechanism.Methods:8 Rhesus macaques were randomly divided into experimental group(n = 4)and control group(n = 4).Experimental animals from Monday to Friday intravenous injection methamphetamine,twice a day,starting quantity is 0.1 mg/kg,increasing 0,1 mg/kg per day,the fourth week reached the target dose of 2.0 mg/kg,maintain to 24 weeks after.Weekly extract blood of rhesus macaques,testing animal serum hormones level.after 24 weeks all animals were killed,collecting animal tissue samples,detecting apoptosis factors(Bcl-2,BAX),the experimental group and control group in mRNA and protein expression level of the difference.Results:(1)HPA axis:there was no significant difference in serum ACTH and cortisol between the experimental group and the control group(p>0.05);(2)HPG axis:there was no significant difference in serum FSH,LH,testosterone and androstenedione between the experimental group and the control group(p>0.05).(3)T4?FT4 and TSH level was significantly higher in MAgroup than control group(p<0.05).There was no significant difference in T3 and FT3(P>0.05)between MA group and the control group.Expression level of Bax mRNAwas significantly higher in MA group than control group(p<0.05).Expression level of Bcl-2 mRNA was lower in MA group than control group,but no significant difference(P=0.11).Expression level of TSH-R mRNA was lower in MA group than control group,but no significant difference(P=0.15).Expression level of Bax protein was significantly higher in MA group than control group(P<0.05).Expression level of Bcl-2 protein was significantly lower in MA group than control group(P<0.05).Expression level of TSH-R protein was significantly lower in MA group than control group(P<0.05).Conclusion(s):1?MA did not cause changes in serum hormones of HPA and HPG axis?2.MA can affect the endocrine function of HPT axis,Serum TSH,T4 and FT4 levels were increased,HE staining showed that thyroid follicular epithelial cells were disordered and lymphocytes infiltrated.The expression levels of Bax mRNA in thyroid tissue were up-regulated,Bax protein was up-regulated,and bcl-2 protein and TSH-R protein were down-regulated.Above conclusion shows that MA can affect the rhesus macaques endocrine function,evident in HPT axis.Elevated serum TSH,T4 and FT4 levels,It may be the effect of MA on the central system,increases the production of TSH.On the other hand,it may induce high expression of Apoptosis gene,mediate tissue damage,and lead to the release of endocrine hormones,which will affect the endocrine function under the combined action of the two.