糖尿病脑病进展过程中多巴胺及去甲肾上腺素变化规律研究  

A study of the changes of dopamine and norepinephrine during the pathogenesi of diabetic e ncephalopathy in rats

作　　者：周雪妍[1] 朱秋香[1] 韩晓文[1] 樊红彬[1] 印晓星[1] 

机构地区：[1]徐州医学院临床药理学教研室,江苏 徐州221004

出　　处：《徐州医学院学报》2015年第6期367-372,共6页Acta Academiae Medicinae Xuzhou

基　　金：国家自然科学基金青年基金（81043001）；徐州医学院优秀人才科研启动基金

摘　　要：目的：探讨糖尿病脑病（ DE）疾病进展过程中多巴胺（ DA）及去甲肾上腺素（ NE）的变化规律及调控机制，为DE的早期诊断提供有参考价值的疾病标志物。方法 SD大鼠随机分为2组，DE组大鼠一次性大剂量腹腔注射链脲佐菌素（ STZ，60 mg／kg）制备疾病模型，正常对照组大鼠给予等量的溶剂。每2周取实验动物的血浆、脑脊液、海马和皮质，高效液相串联质谱仪检测DA和NE在各组织中的浓度水平，实时定量 PCR检测脑组织中神经递质合成、代谢相关限速酶的表达。结果与正常对照组比较，DE组大鼠海马中的DA在STZ给药后第4周显著下调；而在脑脊液、血浆以及皮质中则分别于第6、8、10周出现具有统计学意义的下调趋势。 NE在海马中于第6周出现明显的下调趋势，差异有统计学意义；在皮质和脑脊液中于第8周开始显著下调；而在血浆中至第10周才开始出现具有统计学意义的下调趋势。多巴脱羧酶（ DDC）的表达在STZ大鼠的皮质和海马区域都有显著下调趋势，而儿茶酚胺氧位甲基转移酶（ COMT）则表现为显著上调趋势，差异均具有统计学意义。结论儿茶酚胺类神经递质在DE疾病进展过程中发生了组织特异性的失调，神经递质合成代谢相关限速酶可能是神经递质在体浓度水平变化潜在的调节机制。Objective To investigate the changes of dopamine （ DA） and norepinephrine （ NE） in rats with diabetic encephalopathy （ DE） .Methods A model of type I diabetic mellitus was established using 40 male Sprague-Dawley （SD） rats through a single intraperitoneal injection of STZ （60 mg/kg）.Meanwhile, another 40 age-matched rats were administrated with the same volume of vehicle alone as control .Then,the serum, cerebrospinal fluid （ CSF） , hippocam-pus and cortex were collected from the animals for determination of DA and NE by LC -MSM/S.The relative quantities of enzymes responsible for the synthesis and metabolism of neurotransmitters were measured by real -time quantitive poly-merase chain reaction （ RT-qPCR） .Results Compared with the control rats, diabetic rats presented obvious increases in DA in the hippocampus on Week 4 after administration of STZ, and in the CSF, serum and cortex on Weeks 6, 8 and 10 correspondingly.The levels of NE started to remarkably decline in the hippocampus on Week 6, in the cortex and CSF on Week 8 and in the serum on Week 10.The quantity of dopa decarboxylase （DDC） mRNA was substantially down-regulated in the cortex and hippocampus, while the amount of catechol -O -methyltransferase （ COMT） mRNA was markedly up-regulated.Conclusion A tissue-specific disorder of catechol neurotransmitters is indicated during the pathogenesis of DE, which may be related with the changes of neurotransmitter related enzymes.

关 键 词：糖尿病脑病 去甲肾上腺素 多巴胺 酪氨酸羟化酶 多巴脱羧酶 儿茶酚胺氧位甲基转移酶 

分 类 号：R587.2[医药卫生—内分泌]