噻环乙胺及小型猪复合麻醉剂（XFM）对大鼠不同脑区神经递质含量的影响
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摘要
小型猪作为疾病模型是较为理想的实验动物,为使其更好的应用于医学、生物等领域的科研和临床诊疗,需要为小型猪提供一个良好的麻醉过程。本研究在已完成噻环乙胺及其复合麻醉剂XFM全麻中枢细胞信号转导机制研究的基础上,进一步从神经递质的角度研究噻环乙胺及XFM的全身麻醉作用机制。本实验以噻环乙胺及XFM为受试药物,对大鼠进行全身麻醉,用ELISA、荧光分光光度法和HPLC分别测定大鼠大脑皮层、海马、丘脑、小脑和脑干内ACh、神经肽、单胺类神经递质和氨基酸类神经递质的含量,实验结果如下。
1.噻环乙胺麻醉下,大鼠大脑皮层、海马和丘脑内ACh含量显著降低(P<0.01)。XFM麻醉下,大鼠大脑皮层和丘脑内ACh含量显著降低(P<0.01)。
2.噻环乙胺及XFM麻醉下,大鼠大脑皮层、海马和丘脑内NE和DA含量均显著降低(P<0.01),5-HT的含量显著升高(P<0.01)。
3.噻环乙胺麻醉下,大鼠大脑皮层、海马、丘脑和小脑内Glu含量显著降低(P<0.05或P<0.01),海马、丘脑、小脑和脑干内Gly含量显著升高(P<0.05或P<0.01),各脑区内Asp含量显著降低(P<0.05或P<0.01),GABA含量显著升高(P<0.05或P<0.01)。XFM麻醉下,大鼠大脑皮层、海马、丘脑和小脑内Glu含量显著降低(P<0.01),海马、丘脑和脑干内Gly含量显著升高(P<0.01),各脑区内Asp含量显著降低(P<0.05或P<0.01),GABA含量显著升高(P<0.01)。
4.噻环乙胺麻醉下,大鼠大脑皮层、海马和丘脑内L-Enk、M-Enk和β-EP含量均显著升高(P<0.05或P<0.01),大脑皮层和丘脑内dynA和SP含量均显著升高(P<0.05或P<0.01),脑干内M-Enk、β-EP和dynA含量均显著升高(P<0.05),大脑皮层、丘脑和脑干内OFQ的含量显著降低(P<0.05或P<0.01)。XFM麻醉下,大鼠大脑皮层、海马和丘脑内L-Enk、M-Enk和β-EP含量均显著升高(P<0.05或P<0.01),大脑皮层和丘脑内dynA含量显著升高(P<0.01),丘脑内SP含量显著升高(P<0.01),OFQ含量显著降低(P<0.01)。
实验结果表明,噻环乙胺及XFM对大脑皮层、海马、丘脑、小脑和脑干内ACh、单胺类神经递质、氨基酸类神经递质和神经肽含量的影响可能是其产生全麻作用的重要机制之一。噻环乙胺全麻作用可能与降低大脑皮层、海马和丘脑内ACh、NE、DA、Glu,小脑内Glu,大脑皮层、丘脑和脑干内OFQ,各脑区内Asp含量,同时升高大脑皮层、海马和丘脑内5-HT、L-Enk、M-Enk、β-EP,大脑皮层和丘脑内dynA和SP,脑干内M-Enk、β-EP和dynA,各脑区内GABA和Gly含量有关。而XFM全麻作用可能与降低大脑皮层和丘脑内ACh,大脑皮层、海马和丘脑内NE、DA、Glu,小脑内Glu,丘脑内OFQ,各脑区内Asp含量,同时升高大脑皮层、海马和丘脑内5-HT、L-Enk、M-Enk、β-EP,海马、丘脑和脑干内Gly,升高大脑皮层内dynA,丘脑内dynA和SP,各脑区内GABA含量有关。本实验对进一步研究噻环乙胺及XFM的全麻机制具有参考意义。
The principle focus of this study was to explain the possible molecular mechanisms of tiletamine anesthesia and its compound preparationon (XFM) anesthesia on the central nervous system by investigating the changes of Ach,monoamine neurotransmitter,amino acids neurotransmitter and neuropeptide contents in different encephalic regions(the cerebral cortex, the hippocampus, the thalamus, the cerebellum and the brain stem) in rats were measured respectively by ELISA, fluorescent spectral photometrics, HPLC.The results of this experiment are as follows:
1 After injected intraperitoneally with tiletamine,the ACh contents in the cerebral cortex, the hippocampus and the thalamus were obviously decreased as compared with control group(P<0.01). After injected intraperitoneally with XFM, the ACh contents in the cerebral cortex and the thalamus were obviously decreased as compared with control group(P<0.01).
2 After injected intraperitoneally with tiletamine and XFM, the NE, DA contents in the cerebral cortex, the hippocampus and the thalamus in the anesthesia group were obviously decreased as compared with control group(P<0.01), the 5-HT contents were obviously raised(P<0.01); The NE, DA, 5-HT contents in the cerebellum and the brain stem were not obviously changed in the process of general anesthesia of tiletamine and XFM.
3 After injected intraperitoneally with tiletamine,the Asp and Glu contents in the cerebral cortex were obviously decreased as compared with control group(P<0.01), while the GABA content was significantly increased(P<0.01);the Asp and Glu contents in the hippocampus, the thalamus and the cerebellum were obviously decreased as compared with control group(P<0.05 or P<0.01),while the GABA and the Gly content was significantly increased(P<0.05 or P<0.01);the Asp content in the brain stem were obviously decreased as compared with control group(P<0.05), while the GABA and the Gly content was significantly increased(P<0.05 or P<0.01).After injected intraperitoneally with XFM, the Asp and Glu contents in the cerebral cortex and the cerebellum were obviously decreased as compared with control group(P<0.05 or P<0.01), while the GABA content was significantly increased(P<0.01); The Asp and Glu contents in the hippocampus and the thalamus were obviously decreased as compared with control group(P<0.01),while the GABA and the Gly content was significantly increased(P<0.01); the Asp content in the brain stem were obviously decreased as compared with control group(P<0.01), while the GABA and the Gly content was significantly increased(P<0.01).
4 After injected intraperitoneally with tiletamine,the L-Enk, M-Enk,β-EP , dynA and SP contents in the cerebral cortex and the thalamus in the anesthesia group were obviously increased as compared with control group(P<0.05 or P<0.01), while the OFQ content was significantly decreased(P<0.05 or P<0.01).The L-Enk, M-Enk andβ-EP contents in the hippocampus were obviously increased as compared with control group(P<0.05 or P<0.01).The M-Enk,β-EP and dynA contents in the brainstem were obviously increased as compared with control group(P<0.05 or P<0.01), the OFQ content was obviously decreased(P<0.05).After injected intraperitoneally with XFM,the L-Enk, M-Enk,β-EP and dynA contents in the cerebral cortex in the anesthesia group were obviously increased as compared with control group(P<0.05 or P<0.01), the L-Enk, M-Enk andβ-EP contents in the hippocampus were obviously increased (P<0.05 or P<0.01),the OFQ contents in the thalamus were obviously decreased(P<0.01); The L-Enk, M-Enk,β-EP, dynA, OFQ and SP contents in the thalamus were obviously increased (P<0.05 or P<0.01),the OFQ contents were obviously decreased(P<0.01).
Tiletamine and XFM anesthesia have an effect on the content of Ach, monoamine neurotransmitter, amino acids neurotransmitter and neuropeptide in different encephalic regions. Tiletamine could decrease the ACh content in the cerebral cortex, the hippocampus and the thalamus; decrease the NE and DA contents in the cerebral cortex, the hippocampus and the thalamus,at the same time,increase the 5-HT content; decrease the Asp and Glu contents in the cerebral cortex、the hippocampus, the thalamus and the cerebellum, at the same time,increase the GABA content in the cerebral cortex and the GABA and Gly contents in the hippocampus, the thalamus, the cerebellum and the brain stem; increase the L-Enk, M-Enk,β-EP, dynA and SP contents in the cerebral cortex and the thalamus, increase the L-Enk, M-Enk andβ-EP contents in the hippocampus, increase the M-Enk,β-EP and dynA contents in the brain stem, at the same time,decrease the OFQ content in the cerebral cortex、the thalamus and the brain stem.XFM could decrease the ACh content in the cerebral cortex and the thalamus; decrease the NE and DA contents in the cerebral cortex, the hippocampus and the thalamus,at the same time,increase the 5-HT content; decrease the Asp and Glu contents in the cerebral cortex, the hippocampus, the thalamus and the cerebellum, decrease the Asp content in the brain stem, at the same time,increase the GABA content in the cerebral cortex and the cerebellum, increase the GABA and Gly contents in the hippocampus, the thalamus and the brain stem; increase the L-Enk, M-Enk,β-EP and dynA contents in the cerebral cortex, increase the L-Enk, M-Enk andβ-EP contents in the hippocampus, increase the L-Enk, M-Enk,β-EP, dynA and SP contents in the thalamus, at the same time,decrease the OFQ content in the thalamus.
1.噻环乙胺麻醉下,大鼠大脑皮层、海马和丘脑内ACh含量显著降低(P<0.01)。XFM麻醉下,大鼠大脑皮层和丘脑内ACh含量显著降低(P<0.01)。
2.噻环乙胺及XFM麻醉下,大鼠大脑皮层、海马和丘脑内NE和DA含量均显著降低(P<0.01),5-HT的含量显著升高(P<0.01)。
3.噻环乙胺麻醉下,大鼠大脑皮层、海马、丘脑和小脑内Glu含量显著降低(P<0.05或P<0.01),海马、丘脑、小脑和脑干内Gly含量显著升高(P<0.05或P<0.01),各脑区内Asp含量显著降低(P<0.05或P<0.01),GABA含量显著升高(P<0.05或P<0.01)。XFM麻醉下,大鼠大脑皮层、海马、丘脑和小脑内Glu含量显著降低(P<0.01),海马、丘脑和脑干内Gly含量显著升高(P<0.01),各脑区内Asp含量显著降低(P<0.05或P<0.01),GABA含量显著升高(P<0.01)。
4.噻环乙胺麻醉下,大鼠大脑皮层、海马和丘脑内L-Enk、M-Enk和β-EP含量均显著升高(P<0.05或P<0.01),大脑皮层和丘脑内dynA和SP含量均显著升高(P<0.05或P<0.01),脑干内M-Enk、β-EP和dynA含量均显著升高(P<0.05),大脑皮层、丘脑和脑干内OFQ的含量显著降低(P<0.05或P<0.01)。XFM麻醉下,大鼠大脑皮层、海马和丘脑内L-Enk、M-Enk和β-EP含量均显著升高(P<0.05或P<0.01),大脑皮层和丘脑内dynA含量显著升高(P<0.01),丘脑内SP含量显著升高(P<0.01),OFQ含量显著降低(P<0.01)。
实验结果表明,噻环乙胺及XFM对大脑皮层、海马、丘脑、小脑和脑干内ACh、单胺类神经递质、氨基酸类神经递质和神经肽含量的影响可能是其产生全麻作用的重要机制之一。噻环乙胺全麻作用可能与降低大脑皮层、海马和丘脑内ACh、NE、DA、Glu,小脑内Glu,大脑皮层、丘脑和脑干内OFQ,各脑区内Asp含量,同时升高大脑皮层、海马和丘脑内5-HT、L-Enk、M-Enk、β-EP,大脑皮层和丘脑内dynA和SP,脑干内M-Enk、β-EP和dynA,各脑区内GABA和Gly含量有关。而XFM全麻作用可能与降低大脑皮层和丘脑内ACh,大脑皮层、海马和丘脑内NE、DA、Glu,小脑内Glu,丘脑内OFQ,各脑区内Asp含量,同时升高大脑皮层、海马和丘脑内5-HT、L-Enk、M-Enk、β-EP,海马、丘脑和脑干内Gly,升高大脑皮层内dynA,丘脑内dynA和SP,各脑区内GABA含量有关。本实验对进一步研究噻环乙胺及XFM的全麻机制具有参考意义。
The principle focus of this study was to explain the possible molecular mechanisms of tiletamine anesthesia and its compound preparationon (XFM) anesthesia on the central nervous system by investigating the changes of Ach,monoamine neurotransmitter,amino acids neurotransmitter and neuropeptide contents in different encephalic regions(the cerebral cortex, the hippocampus, the thalamus, the cerebellum and the brain stem) in rats were measured respectively by ELISA, fluorescent spectral photometrics, HPLC.The results of this experiment are as follows:
1 After injected intraperitoneally with tiletamine,the ACh contents in the cerebral cortex, the hippocampus and the thalamus were obviously decreased as compared with control group(P<0.01). After injected intraperitoneally with XFM, the ACh contents in the cerebral cortex and the thalamus were obviously decreased as compared with control group(P<0.01).
2 After injected intraperitoneally with tiletamine and XFM, the NE, DA contents in the cerebral cortex, the hippocampus and the thalamus in the anesthesia group were obviously decreased as compared with control group(P<0.01), the 5-HT contents were obviously raised(P<0.01); The NE, DA, 5-HT contents in the cerebellum and the brain stem were not obviously changed in the process of general anesthesia of tiletamine and XFM.
3 After injected intraperitoneally with tiletamine,the Asp and Glu contents in the cerebral cortex were obviously decreased as compared with control group(P<0.01), while the GABA content was significantly increased(P<0.01);the Asp and Glu contents in the hippocampus, the thalamus and the cerebellum were obviously decreased as compared with control group(P<0.05 or P<0.01),while the GABA and the Gly content was significantly increased(P<0.05 or P<0.01);the Asp content in the brain stem were obviously decreased as compared with control group(P<0.05), while the GABA and the Gly content was significantly increased(P<0.05 or P<0.01).After injected intraperitoneally with XFM, the Asp and Glu contents in the cerebral cortex and the cerebellum were obviously decreased as compared with control group(P<0.05 or P<0.01), while the GABA content was significantly increased(P<0.01); The Asp and Glu contents in the hippocampus and the thalamus were obviously decreased as compared with control group(P<0.01),while the GABA and the Gly content was significantly increased(P<0.01); the Asp content in the brain stem were obviously decreased as compared with control group(P<0.01), while the GABA and the Gly content was significantly increased(P<0.01).
4 After injected intraperitoneally with tiletamine,the L-Enk, M-Enk,β-EP , dynA and SP contents in the cerebral cortex and the thalamus in the anesthesia group were obviously increased as compared with control group(P<0.05 or P<0.01), while the OFQ content was significantly decreased(P<0.05 or P<0.01).The L-Enk, M-Enk andβ-EP contents in the hippocampus were obviously increased as compared with control group(P<0.05 or P<0.01).The M-Enk,β-EP and dynA contents in the brainstem were obviously increased as compared with control group(P<0.05 or P<0.01), the OFQ content was obviously decreased(P<0.05).After injected intraperitoneally with XFM,the L-Enk, M-Enk,β-EP and dynA contents in the cerebral cortex in the anesthesia group were obviously increased as compared with control group(P<0.05 or P<0.01), the L-Enk, M-Enk andβ-EP contents in the hippocampus were obviously increased (P<0.05 or P<0.01),the OFQ contents in the thalamus were obviously decreased(P<0.01); The L-Enk, M-Enk,β-EP, dynA, OFQ and SP contents in the thalamus were obviously increased (P<0.05 or P<0.01),the OFQ contents were obviously decreased(P<0.01).
Tiletamine and XFM anesthesia have an effect on the content of Ach, monoamine neurotransmitter, amino acids neurotransmitter and neuropeptide in different encephalic regions. Tiletamine could decrease the ACh content in the cerebral cortex, the hippocampus and the thalamus; decrease the NE and DA contents in the cerebral cortex, the hippocampus and the thalamus,at the same time,increase the 5-HT content; decrease the Asp and Glu contents in the cerebral cortex、the hippocampus, the thalamus and the cerebellum, at the same time,increase the GABA content in the cerebral cortex and the GABA and Gly contents in the hippocampus, the thalamus, the cerebellum and the brain stem; increase the L-Enk, M-Enk,β-EP, dynA and SP contents in the cerebral cortex and the thalamus, increase the L-Enk, M-Enk andβ-EP contents in the hippocampus, increase the M-Enk,β-EP and dynA contents in the brain stem, at the same time,decrease the OFQ content in the cerebral cortex、the thalamus and the brain stem.XFM could decrease the ACh content in the cerebral cortex and the thalamus; decrease the NE and DA contents in the cerebral cortex, the hippocampus and the thalamus,at the same time,increase the 5-HT content; decrease the Asp and Glu contents in the cerebral cortex, the hippocampus, the thalamus and the cerebellum, decrease the Asp content in the brain stem, at the same time,increase the GABA content in the cerebral cortex and the cerebellum, increase the GABA and Gly contents in the hippocampus, the thalamus and the brain stem; increase the L-Enk, M-Enk,β-EP and dynA contents in the cerebral cortex, increase the L-Enk, M-Enk andβ-EP contents in the hippocampus, increase the L-Enk, M-Enk,β-EP, dynA and SP contents in the thalamus, at the same time,decrease the OFQ content in the thalamus.
引文
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