小鼠前扣带回皮质内THBS4在神经病理性痛中的表达变化

Expression changes of THBS4 in the anterior cingulate cortex under neuropathic pain of mice

目的:探讨前扣带回皮质(ACC)中的血小板反应蛋白4(THBS4)在小鼠神经病理性疼痛中的表达变化情况。方法:利用免疫荧光染色方法观察正常小鼠ACC脑区THBS4的表达分布情况。将雄性健康小鼠随机分成假手术组(Sham组)和实验组(SNI组),通过选择性神经损伤(SNI)方法建立神经病理性疼痛小鼠模型,采用机械刺激和热辐射刺激方法分别检测小鼠的机械缩足阈值(PWT)和热缩足潜伏期(PWL)。采用Western Blot方法检测小鼠ACC脑区THBS4蛋白表达变化情况。结果:THBS4在小鼠ACC脑区广泛分布,在兴奋性和抑制性神经元都有表达,但主要在兴奋性神经元中表达。小鼠在建立SNI模型后,其同侧足底在7和56 d均出现了稳定的机械痛和热痛敏化现象。Western Blot实验显示,与sham组相比,SNI后ACC脑区THBS4的表达水平显著下调。结论:THBS4大量表达于小鼠ACC,主要与兴奋性神经元共标。SNI模型小鼠ACC脑区中THBS4蛋白表达水平显著下调,提示ACC脑区中THBS4可能参与介导了神经病理性疼痛的发生发展过程。

Objective:To investigate the expression of thrombospondin 4(THBS4)in the anterior cingulate cortex(ACC)of mice following nerve injury.Methods:The expression profile of THBS4 in the ACC of normal mice was detected by immunofluorescence staining.Healthy male mice were randomly divided into sham group and spared nerve injury(SNI)group.To mimic clinical neuropathic pain,we used a previously described SNI model.Mechanical paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were by von Frey hairs and thermal radiation stimulation,respectatively.Western Blot was used to detect the protein level of THBS4 in ACC.Results:THBS4 was widely distributed in the ACC of mice,and was expressed in both excitatory and inhibitory neurons,but mainly in excitatory neurons.Following SNI surgery,mice developed persistent mechanical and thermal pain hypersensitivity in the ipsilateral hindpaw at 7 and 56 d post injury.Western Blot analysis showed that the expression of THBS4 in the ACC was downregulated after SNI as compared with sham group.Conclusion:THBS4 was mainly expressed in the ACC of mice,and mainly co-labeled with excitatory neurons.The expression level of THBS4 in the ACC was significantly decreased after SNI.These data suggest that THBS4 in the ACC may play a role in the development of neuropathic pain.