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目的探讨蠕虫来源的免疫调控性糖分子乳-N-岩藻五糖Ⅲ(lacto-N-fucopentaoseⅢ,LNFPⅢ)对成年大鼠胫神经永久性横断伤(即改良型备用性神经损伤,modified spared nerve injury,mSNI)后神经病理性疼痛的病理发生的影响,以及它对此时脊髓胶质细胞活化的影响。方法成年雄性SD大鼠随机分为4组,即假手术组(n=6)、mSNI手术组(n=6)、mSNI手术+牛血清白蛋白(BSA)组(n=12)和mSNI手术+LNFPⅢ组(n=12)。各组动物行右侧mSNI手术或者相应的假手术,根据实验分组腹腔注射BSA或LNFPⅢ与BSA的结合物。每组取6只大鼠进行足底试验、von Frey纤维试验、针刺试验和丙酮试验,测试手术前、后手术同侧和对侧大鼠后爪足底面腓肠神经和隐神经皮肤区域特异性的疼痛反应。制备mSNI手术+BSA组和mSNI手术+LNFPⅢ组手术后7d和14d(各组每个时间点3只动物)的第3~第4腰椎(L3~4)脊髓节段冰冻切片,进行小胶质/巨噬细胞标志物分化抗原簇分子11b(cluster of differentiation molecule 11b,CD11b)和星形胶质细胞标志物胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)的免疫荧光染色。结果成年大鼠mSNI后,早期系统性给予LNFPⅢ可显著缓解手术后急性诱导期(4/5d)和慢性转化期(7/8d和14/15d)中手术侧后爪足底面腓肠神经和隐神经皮肤区域特异性的机械和温度刺激诱发的病理性疼痛。同时,早期系统性给予LNFPⅢ抑制mSNI大鼠手术侧脊髓背角中术后7d小胶质/巨噬细胞以及术后7d和14d星形胶质细胞的活化。结论早期系统性给予LNFPⅢ能抑制成年大鼠mSNI后神经病理性疼痛的病理发生(包括急性诱发和慢性转化)以及该过程中脊髓胶质细胞的活化。
Objective To investigate the effects of lacto-N-fucopentaose Ⅲ (LNFPⅢ), a worm-derived immunomodulatory drug, on the permanent tibial nerve transection (ie, modified spared nerve injury, mSNI) and its effect on the activation of the spinal cord astrocytes at this time. Methods Adult male SD rats were randomly divided into 4 groups: sham operation group (n = 6), mSNI operation group (n = 6), mSNI operation + bovine serum albumin (BSA) group + LNFP group (n = 12). Each group of animals underwent right mSNI surgery or the corresponding sham operation, according to the experimental group of intraperitoneal injection of BSA or LNFP Ⅲ and BSA conjugates. Six rats in each group were subjected to plantar test, von Frey fiber test, acupuncture test and acetone test to examine the sural nerve and saphenous nerve skin areas on the plantar surface of the hindpaw of the ipsilateral and contralateral rats before and after surgery Sexual pain response. Frozen sections of spinal cord segments from the third to the fourth lumbar vertebrae (L3-4) of mSNI + BSA group and mSNI + LNFP Ⅲ group at 7d and 14d after operation (3 animals at each time point) / Macrophage marker cluster of differentiation molecule 11b (CD11b) and astrocyte marker glial fibrillary acidic protein (GFAP). Results In the early stage of mSNI, the systemic administration of LNFPⅢ could significantly relieve the sural nerve sulcus of the posterior hindpaw in the acute phase (4/5 days) and the chronic transformation phase (7/8 days and 14/15 days) Neuronal skin-specific mechanical and temperature-induced pathological pain. In the meantime, the early systematic administration of LNFPIII inhibited microglial / macrophages in the dorsal horn of spinal cord of the operated side of mSNI rats and the activation of astrocytes 7d and 14d after operation. CONCLUSION: Early systemic administration of LNFPIII suppresses the pathogenesis of neuropathic pain (including acute induction and chronic conversion) and activation of spinal glial cells in adult rats following mSNI.