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Heroin Affects Purine Nucleotides Catabolism In Brain

Posted on:2006-04-09Degree:MasterType:Thesis
Country:ChinaCandidate:P X ChengFull Text:PDF
GTID:2144360155453453Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Abusage and prevalence of drugs and dopes is one of the important social problems. Up to now, the mechanism of tolerance, addiction, and withdrawal of opioid is not thoroughly clear, so there is no effective approach to radical cure the addition of it. At present, the animal model of morphine and heroin is used widely, but the effect of heroin is not the same as morphine, furthermore the toxicity of heroin is more serious than that of morphine, therefore a rat model of heroin addiction was established in our investigation. The experimental result is shown below: 1. The variance of plasma uric acid content: Compared with that of the control group, the contents of plasma uric acid in the 3-day heroin administration group and the 9-day heroin administration group increased significantly (P<0.01),and those of the 3-day withdrawal group and the 8-day withdrawal group were still higher than that of the control group(P>0.05). Compared with the 3-day heroin administration group, the plasma uric acid contents of the 3-day withdrawal group and the 8-day withdrawal group decreased(P<0.05). The increase of plasma uric acid manifested purine nucleotides catabolism was enhanced in rats with heroin addiction, thus it led to the increase of plasma uric acid. 2. The variance of enzyme content: (1) The variance of enzyme content in plasma: I. The result of plasma ADA: Compared with that of the control group, the ADA contents of the 3-day heroin administration group and the 9-day heroin administration group increased significantly (P<0.01). The ADA contents in the 3-day withdrawal group and the 8-day withdrawal group were still higher than that of the control group(P<0.01), but the content in the 8-day withdrawal group decreased apparently as compared with the 3-day withdrawal group. II. The result of plasma XOD: Compared with that of the control group, there was an increasing tendency in the 3-day heroin administration group(P>0.05),and the XOD content ofthe 9-day heroin administration group was higher than that of the control group. There was no significant difference when the 3-day withdrawal group and the 8-day withdrawal group were compared with the control group. The XOD contents of the two withdrawal groups were higher than that of the 9-day heroin administration group. Compared with the control group, the ADA and XOD concentrations of the 3-day heroin administration group and the 9-day heroin administration group increased and it demonstrated that heroin administration caused the enhancement of enzymes. Compared with the 9-day heroin administration group, the ADA contents in the two withdrawal groups kept in high level, while the XOD contents decreased. It showed that XOD content recovered soon, while it might take a longer time for the content of ADA to recover. ADA and XOD are intracellular enzymes, so the variance of enzyme in plasma must be caused by some tissues. Because the addiction of heroin relates to central nerves system, we detected the contents of ADA and XOD in cerebrum and cerebellum, and theresult might reflect the effect of heroin directly. (2) The variance of enzyme content in cerebrum: I. The result of cerebrum ADA: Compared with the control group, the ADA concentration of the 3-day heroin administration group increased, but it was not significant(P>0.05), while the 9-day heroin administration group increased apparently(P<0.01). There was no significant difference when the 3-day withdrawal group and the 8-day withdrawal group were compared with the control group(P>0.05). Compared with the 9-day heroin administration group, there was a decrease in the ADA content of the 3-day withdrawal group, but it was not significant (P>0.05), while the ADA content of the 8-day withdrawal group decreased apparently(P<0.01). II. The result of cerebrum XOD: Compared with the control group, there was an increasing tendency in the XOD concentration of the 3-day heroin administration group, but it was not significant(P>0.05), while that of the 9-day heroin administration group increased apparently(P<0.01). The XOD contents of the 3-day withdrawal group and the 8-daywithdrawal group were still higher than that of the control group, but it was not significant(P>0.05). Compared with the 9-day heroin administration group, there was a decreasing tendency of XOD content in the 3-day withdrawal group, but it was not apparent(P>0.05), while the XOD content of the 8-day withdrawal group was lower than that of the 9-day heroin administration group(P<0.05). Compared with the control group, the ADA and XOD contents of the 3-day heroin administration group increased in cerebrum, but it was not apparent. With the time prolongation and dosage increase, the contents of ADA and XOD were significantly higher than that of the control group. Compared with the 9-day heroin administration group, the decrease of the ADA and XOD contents was not apparent in the 3-day withdrawal group, while the enzyme contents of the 8-day withdrawal group decreased significantly. The enzymes of the two withdrawal groups were slightly higher than that of the control group, but it was not significant. It demonstrated that with the time prolongation of heroin administration, theenzyme contents decreased gradually to the normal level. (3) The variance of enzyme content in cerebellum: I. The result of cerebellum ADA: Compared with the control group, the ADA concentration of the 3-day heroin administration group and the 9-day heroin administration group increased apparently(P<0.05). The ADA contents of the 3-day withdrawal group and the 8-day withdrawal group were higher than that of the control group, but it was not apparent (P>0.05). Compared with the 9-day heroin administration group, the ADA contents of the two withdrawal groups decreased, but it was not apparent(P>0.05). II. The result of cerebellum XOD: Compared with the control group, the XOD contents of the two heroin administration groups were significantly increased(P<0.01), those of the two withdrawal groups were still higher than that of the control group, but it was not apparent(P>0.05). Compared with that of the 9-day heroin administration group, the XOD contents of the 3-day withdrawal group and the 8-day withdrawal group decreased, but it was not apparent(P>0.05).Compared with that of the control group, the enzyme contents of the two heroin administration groups increased. Compared with that of the heroin administration group, there was a decreasing tendency in the enzyme contents of the two withdrawal groups, but it was not apparent, furthermore those of the two withdrawal groups were still higher than that of the control group. It demonstrated that the effect of heroin on ADA and XOD in cerebellum was more significant and lasted for a longer time. The result shown above demonstrated that heroin caused the enhancement of ADA and XOD contents in bran tissue, thus it induced the augment of purine nucleotide catabolism and then the content of plasma uric acid increased. During withdrawal, the enzyme contents of the cerebrum and cerebellum decreased gradually, but it was slow in cerebellum. Heroin produced different effects on different encephalic regions and the influence on cerebellum was tougher. 3. The variance of mRNA: To approach the essential qualities of ADA and XOD increase,the mRNA contents of the two enzymes were detected. (1) The variance of enzyme mRNA content in cerebrum: I. The result of cerebrum ADA mRNA: Compared with the control group, the ADA concentration of the 3-day heroin administration group increased and the increase of the 9-day heroin administration group was more apparent. The 3-day withdrawal group was still higher than the control group; while the 8-day withdrawal group was a little lower than that of the control group. Compared with the 9-day heroin administration group, the ADA mRNA content of the 3-day withdrawal group decreased and the decrease of the 8-day withdrawal group was more apparent. The result showed that the variation tendency of ADA mRNA paralleled to the variance of enzyme. Heroin might produce an effect on the transcriptional level and led to the enhancement of enzyme in cerebrum. II. The result of cerebrum XOD mRNA: Compared with the control group, the XOD mRNA content of the 3-day heroin administration group increased and the enhancement in the9-day heroin administration group was more apparent. The XOD mRNA contents in the two withdrawal groups were still significantly higher than that of the control group. Compared with the 9-day heroin administration group, the XOD mRNA contents of the two withdrawal groups decreased. The result showed that the variance tendency of the XOD mRNA was similar to that of the enzyme. The XOD mRNA content was still higher than that of the control group, but the enzyme content was no longer higher. It might because the enhancement on the transcriptional level was no longer predominant and the enzyme cleaned up from plasma fast, thus the decline of the enzyme was sooner. The result still demonstrated that the enhancement of the enzyme had relation to the gene transcription. (2) The variance of enzyme mRNA content in cerebellum: I. The result of cerebellum ADA mRNA: Compared with the control group, the ADA mRNA concentrations of the 3-day heroin administration group and the 9-day heroin administration group increased apparently and the enhancement of the 9-dayheroin administration group was more significant. The mRNA contents of the 3-day withdrawal group and the 8-day withdrawal group were still higher than that of the control group. Compared with that of the 9-day heroin administration group, the ADA mRNA contents of the two withdrawal groups decreased significantly. The result showed that the variance tendency of the enzyme parallel to that of the mRNA. II. The result of cerebellum XOD mRNA: Compared with the control group, the XOD concentration of the 3-day heroin administration group already increased and the increase of the 9-day heroin administration group was more apparent. The result showed that both of the contents of XOD and XOD mRNA increased. During withdrawal, the XOD mRNA contents decreased gradually and the enzyme concentrations gradually recovered to normal. In summary, heroin administration caused the enhancement of ADA and XOD mRNA contents in brain tissue and then ADA and XOD increased. Consequently, it promoted the catabolism of purine nucleotides and then induced the enhancement of the...
Keywords/Search Tags:Nucleotides
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