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小剂量右美托咪定缓解大鼠慢性疼痛相关抑郁样行为及对前额叶皮质N-甲基-D-天冬氨酸受体2B亚基的影响
刘国,费艳霞,罗科,杨金凤*,苏晨*
0
(中南大学湘雅医学院附属肿瘤医院麻醉科, 长沙 410013
*通信作者)
摘要:
目的 观察小剂量右美托咪定对慢性疼痛大鼠抑郁样行为及前额叶皮质(PFC)N-甲基-D-天冬氨酸受体2B亚基(NR2B)的影响。方法 将22只成年大鼠随机分为假手术组(Sham组,n=6)、保留性神经损伤组(SNI组,n=6)、保留性神经损伤+生理盐水组(SNI+NS组,n=5)和保留性神经损伤+右美托咪定组(SNI+DEX组,n=5)。SNI+NS组及SNI+DEX组在建模后第8~14天腹腔注射等体积生理盐水或小剂量DEX(20 μg/kg)。采用von Frey纤维评估大鼠疼痛缩足阈值(PWT),强迫游泳实验(FST)评估大鼠抑郁样行为,蛋白质印迹法检测大鼠PFC中NR2B蛋白的表达。结果 与Sham组相比,SNI组大鼠术后第1、3、7、14天PWT降低,术后第15天FST中右腿不动时间延长、PFC中NR2B蛋白表达降低,差异均有统计学意义(P<0.01,P<0.01,P<0.05)。与SNI+NS组相比,SNI+DEX组大鼠术后第1~14天PWT无明显变化(P>0.05),术后第15天FST中右腿不动时间缩短、PFC中NR2B蛋白表达增加(P<0.01、P<0.05)。结论 腹腔内注射小剂量DEX可缓解大鼠慢性疼痛相关的抑郁样行为,其机制可能与PFC中NR2B蛋白的增加有关。
关键词:  右美托咪定  神经病理性疼痛  N-甲基-D-天冬氨酸受体2B亚基  抑郁样行为  前额叶皮质
DOI:10.16781/j.0258-879x.2020.07.0775
投稿时间:2020-04-20修订日期:2020-05-09
基金项目:湖南省自然科学基金(2017JJ3194).
Effects of low-dose dexmedetomidine on chronic pain-related depression-like behavior and N-methyl-D-aspartate receptor 2B subunit in the prefontal cortex in rats
LIU Guo,FEI Yan-xia,LUO Ke,YANG Jin-feng*,SU Chen*
(Department of Anesthesiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China
*Corresponding authors)
Abstract:
Objective To observe the effects of low-dose dexmedetomidine (DEX) on chronic pain-related depression-like behavior in rats and on the N-methyl-D-aspartate receptor 2B subunit (NR2B) in the prefontal cortex (PFC). Methods Twenty-two adult rats were randomly divided into Sham group (n=6), spared nerve injury (SNI) group (n=6), SNI+normal saline (NS) group (n=5) and SNI+DEX group (n=5). All rats of SNI+NS group and SNI+DEX group were intraperitoneally injected with an equal volume of NS or low-dose DEX (20 μg/kg) within 8-14 days after modeling. The von Frey test was used to evaluate the pain withdrawal threshold (PWT), and force swim test (FST) was used to evaluate rats' depression-like behavior. The expression of NR2B in PFC of rats was detected by Western blotting. Results Compared with the Sham group, the rats in SNI group had decreased PWT on day 1, 3, 7 and 14 after surgery, increased right leg immobility time and decreased NR2B protein expression in PFC on day 15 after surgery, and the differences were statistically significant (P<0.01, P<0.01, P<0.05). Compared with the SNI+NS group, the PWT of SNI+DEX group showed no significant changes (P>0.05) on day 1 to day 14 after surgery, the right leg immobility time in FST on day 15 after surgery was significantly decreased (P<0.01), and the expression of NR2B in PFC was significantly increased (P<0.05). Conclusion Intraperitoneal injection of a low-dose DEX may alleviate depression-like behavior associated with chronic neuropathic pain in rats, and the mechanism may be related to the increase of NR2B protein in PFC.
Key words:  dexmedetomidine  neuropathic pain  N-methyl-D-aspartate receptor 2B subunit  depression-like behavior  prefrontal cortex