【摘要】 目的 建立慢性应激状态下糖尿病大鼠模型,并应用~1H NMR方法研究其海马的代谢物含量变化。方法 采用一次性腹腔注射链脲佐菌素(STZ) 64mg/kg方法将20只Wistar大鼠诱导糖尿病,成模后将大鼠随机分为糖尿病组(DM组,n=6只)及糖尿病慢性应激组(DC组,n=14只)。此后,DC组采用28d慢性不可预见性轻度应激(CUMS)方法制备慢性应激状态下糖尿病大鼠模型。随后,利用Open-field及Morris水迷宫实验观察两组大鼠行为学变化。行为学实验后,提取两组大鼠海马组织并利用~1H NMR方法检测其代谢物含量变化。结果 两组大鼠进食及饮水量增加,消瘦,毛色晦暗,DC组大鼠精神萎靡,反应迟钝,二便增多。两组大鼠在应激前后均始终保持高水平随机血糖(>33.3mol/L)。应激前后,两组大鼠体质量随时间的推移均呈下降趋势,两组之间体质量差异无统计学意义(P>0.05)。Open-field实验显示DC组大鼠总路程、活动时间及活动次数均明显少于DM组(P<0.05),在Morris水迷宫空间探索实验中,DC组大鼠站台穿越次数明显少于DM组大鼠(P<0.05)。~1H NMR方法测得两组大鼠海马中代谢物含量变化,DC组大鼠海马中的谷氨酸及谷氨酰胺水平较DM组明显升高(P<0.05)。结论 慢性应激状态下糖尿病大鼠海马中的谷氨酸及谷氨酰胺水平与单纯糖尿病大鼠有显著差异,有助于对糖尿病合并抑郁发病机制的研究。更多还原

【Abstract】 Objective To establish a rat model of diabetes under chronic stress exposure,and observe metabolic alterations in hippocampus of these rats using ~1H nuclear magnetic resonance(~1H NMR).Methods Twenty Wistar rats were injected intraperitoneally with STZ(64 mg/kg)to induce diabetic model.Then,rats were randomly divided into two groups,diabetes mellitus group(Group DM,n=6) and diabetes exposed to CUMS group(Group DC,n=14).Group DC was then exposed to a variable sequence of mild,unpredictable stressors for 28 days.All rats were submitted to the open-filed test and Morris water maze test immediately after the CUMS procedure.After hippocampus samples collection,they were submitted to ~1H NMR to find out metabolic changes between tow groups.Results All animals exhibited classic diabetic signs of weight loss,hyperphagia,polydipia,gloomy hair and increasing urine and stool,Group DC showed mental fatigue and slow response.Both groups kept high blood glucose level(>33.3 mol/L) throughout the study.Both groups failed to gain any weight,and body weights remained to show no statistical significance between two groups(P>0.05).Group DC exhibited an impressive reduction in total distance traveled,activity time and times of locomotion compared with Group DM in the open-field test(P<0.05),and showed obviously fewer times of crossing the former platform area in the probe trial of Morris water maze test(P<0.05).Levels of Glutamate and Glutamine were markedly elevated in Group DC compared with Group DM according to the metabolites in hippocampus samples extracted from both groups measured by ~1H NMR(P<0.05).Conclusion Levels of Glutamate and Glutamine in diabtic rats exposed to chronic stress are significantly different form diabetic rats,which is helpful for understanding the underlying pathogenesis of diabetes combined depression.更多还原