发育期大鼠神经病理性痛诱发远期认知功能障碍时大脑前额叶皮层葡萄糖代谢的变化

Changes in glucose metabolism in prefrontal cortex during long-term cognitive dysfunction induced by neuropathic pain in developing rats

目的评价发育期大鼠神经病理性痛诱发远期认知功能障碍时大脑前额叶皮层葡萄糖代谢的变化。方法SPF级健康雄性SD大鼠,4周龄,体重80~100 g,采用坐骨神经选择性损伤法建立大鼠神经病理性痛模型。分别于造模前1 d(T_(0))和造模后1、3、7、14、28、42、56 d(T_(1~7))时测定术侧足机械缩足反应阈(MWT)。根据T_(5)时与T_(0)时MWT比较的结果,将大鼠分为神经病理性痛组(NP组)和非神经病理性痛组(NNP组)。T_(7)时行旷场实验和新物体识别实验检测大鼠焦虑样行为和认知功能,采用PET/CT检测大脑前额叶皮层18氟-氟代脱氧葡萄糖标准摄取值,分别采用Western blot法和免疫荧光法检测前额叶皮层葡萄糖转运蛋白3表达水平。结果与T_(0)时比较,NNP组T_(1)~2时MWT降低,NP组T_(1~7)时MWT降低(P<0.05)。与NNP组比较,NP组T_(1~7)时MWT降低,T_(7)时中央区停留时间缩短,新物体探索时间百分比降低,前额叶皮层18氟-氟代脱氧葡萄糖标准摄取值降低,葡萄糖转运蛋白3表达下调(P<0.05)。结论发育期大鼠神经病理性痛诱发远期认知功能障碍可能与大脑前额叶皮层葡萄糖代谢降低有关。

Objective To evaluate the changes in glucose metabolism in the prefrontal cortex during long-term cognitive dysfunction induced by neuropathic pain in developing rats.Methods SPF healthy male Sprague-Dawley rats,aged 4 weeks,weighing 80-100 g,were used in this study.The model of neuropathic pain was established by using spared nerve injury in anesthetized rats.The mechanical paw withdrawal threshold(MWT)was measured at 1 day before establishing the model(T_(0))and 1,3,7,14,28,42 and 56 days after establishing the model(T_(1-7)).According to the results of MWT compared between T_(5)and T_(0),the rats were divided into neuropathic pain group(group NP)and non-neuropathic pain group(group NNP).Open field test and novel object recognition test were performed at T_(7)to assess anxiety-like behavior and cognitive function.Positron emission tomography/computed tomography imaging was performed to determine the standard uptake value of 18F-fluorodeoxyglucose in the prefrontal cortex.Then the rats were sacrificed,and prefrontal cortex was removed for determination of the expression of glucose transporter 3 using Western blot and immunofluorescence.Results Compared with the baseline at T_(0),the MWT at T_(1)-2 in group NNP and at T_(1-7)in group NP were significantly decreased(P<0.05).Compared with group NNP,the MWT at T_(1-7)were significantly decreased,the time of staying at the central region at T_(7)was shortened,the percentage of time for exploring the novel object was decreased,the percentage of novel object exploration was decreased,the standard uptake value of 18F-fluorodeoxyglucose in prefrontal cortex was decreased,and the expression of glucose transporter 3 in prefrontal cortex was down-regulated in group NP(P<0.05).Conclusion Long-term cognitive dysfunction induced by neuropathic pain may be related to decreased glucose metabolism in the prefrontal cortex of the developing rats.