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目的:建立并评估可量化型小鼠坐骨神经缩窄性神经病理痛模型。方法:用分级坐骨神经结扎的方法建立动物模型,即将小鼠随机分为N0、N1、N2、N4组,暴露坐骨神经主干部位,N1、N2、N4组小鼠分别结扎坐骨神经1、2、4道,每个结之间间隔1 mm;N0组只游离神经,不作任何结扎。通过测定小鼠右后爪热痛阈值,电镜观察坐骨神经超微结构,免疫组化检测小胶质细胞OX-42的荧光积分光密度值(IOD),酶联免疫吸附(ELISA)法测定脊髓白介素(IL-1β、IL-6)和肿瘤坏死因子(TNF-α)的浓度对模型进行评估。结果:与N0组相比,N1、N2和N4组术后热痛阈值较术前明显下降,坐骨神经纤维广泛洋葱化改变,轴索溶解或消失,雪旺氏细胞水肿、坏死,异常髓鞘所占比例增加,脊髓IL-1β、IL-6和TNF-α表达不同程度上升;N2、N4组脊髓小胶质细胞OX-42的IOD显著增加。结论:小鼠可量化型坐骨神经缩窄模型呈现不同程度的神经病理性疼痛、坐骨神经不同程度的髓鞘病变、脊髓小胶质细胞活化及脊髓IL-1β、IL-6和TNF-α表达增加;这一模型的建立可为神经病理性疼痛等的研究提供更利于准确评估的病理模型。
OBJECTIVE: To establish and evaluate a quantifiable mouse model of constrictive neuropathic pain with sciatic nerve. Methods: Animal models were established by graded sciatic nerve ligation. The mice were randomly divided into N0, N1, N2 and N4 groups. The sciatic nerve trunk was exposed. N1, N2 and N4 mice were ligated with 1, 2, Each knot interval 1 mm; N0 group only free nerve, without any ligation. The threshold of heat pain in the right hind paw of mice was measured, the sciatic nerve ultrastructure was observed by electron microscope, the fluorescence integral optical density (IOD) of microglia OX-42 was detected by immunohistochemistry, and the content of interleukin (IL-1β, IL-6) and tumor necrosis factor (TNF-α) concentrations in the model. Results: Compared with the preoperative N0 group, the pain thresholds of N1, N2 and N4 group were significantly lower than those of the preoperative N0 group. The sciatic nerve fibers had extensive onions change, axonal dissolution or disappearance, Schwann cell edema, necrosis and abnormal myelin sheath The proportion of IL-1β, IL-6 and TNF-α in spinal cord increased to some extent. The IOD of OX-42 in spinal cord microglia of N2 and N4 groups increased significantly. CONCLUSION: The mouse model of quantified sciatic nerve constriction shows varying degrees of neuropathic pain, varying degrees of myelin sheath sciatic nerve injury, activation of spinal cord microglia and increased expression of IL-1β, IL-6 and TNF-α in the spinal cord The establishment of a model can provide a more accurate pathological model for the study of neuropathic pain and the like.