原儿茶酸对大鼠慢性神经病理性疼痛的影响及其机制研究  

Effect of protocatechuic acid on chronic neuropathic pain and its mechanism in rats

作　　者：姜开洋[1] 董莉丽 李俊飞 张丽[1] 潘桢婕 Jiang Kaiyang;Dong Lili;Li Junfei;Zhang Li;Pan Zhenjie(Department of Pain,Nanyang Central Hospital,Nanyang 473000,China;Department of Pharmacy,Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]南阳市中心医院疼痛科,南阳473000 [2]郑州大学第二附属医院药学部,郑州450000

出　　处：《中华神经医学杂志》2022年第8期782-788,共7页Chinese Journal of Neuromedicine

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20190331)。

摘　　要：目的探讨原儿茶酸对大鼠慢性神经病理性疼痛的影响及其机制。方法取32只SD大鼠,采用坐骨神经结扎法制备成神经病理性疼痛模型,并按随机数字表法分为模型组、原儿茶酸低剂量组、原儿茶酸高剂量组和布洛芬组,每组8只。造模后第3天开始,后3组大鼠分别经颈静脉注射给予10、20 mg/kg原儿茶酸溶液及灌胃给予20 mg/kg布洛芬片,1次/d、连续21 d。另取8只SD大鼠设为假手术组,仅游离坐骨神经但不结扎。给药期间持续观察各组大鼠的行为学表现,并于给药后第7、14、21天分别用von-Frey型测痛仪测定大鼠后足机械痛阈以及用BME-410A热痛刺激仪测定热痛阈,随后立即处死大鼠,应用ELISA法检测大鼠血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平,应用TUNEL染色观察大鼠脊髓组织细胞凋亡情况,应用Western blotting实验检测大鼠脊髓组织中核转录因子-κB(NF-κB)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路相关蛋白的表达。结果(1)给药后第7、14、21天,与假手术组比较,模型组大鼠的后足机械痛阈、热痛阈明显降低,差异均有统计学意义(P<0.05);与模型组比较,原儿茶酸低剂量组、原儿茶酸高剂量组、布洛芬组大鼠的后足机械痛阈、热痛阈明显升高,差异均有统计学意义(P<0.05);与原儿茶酸低剂量组比较,原儿茶酸高剂量组、布洛芬组大鼠的后足机械痛阈、热痛阈明显升高,差异均有统计学意义(P<0.05);与原儿茶酸高剂量组比较,布洛芬组大鼠的后足机械痛阈、热痛阈明显升高,差异均有统计学意义(P<0.05)。(2)给药后第21天,与假手术组比较,模型组大鼠血清中TNF-α、IL-1β水平及脊髓组织凋亡细胞数量明显升高,差异均有统计学意义(P<0.05);与模型组比较,原儿茶酸低剂量组、原儿茶酸高剂量组、布洛芬组大鼠血清中TNF-α、IL-1β水平及脊髓组织凋亡细胞数量明显降低,差异均有统�Objective To investigate the effect of protocatechuic acid on chronic neuropathic pain(NP)and its mechanism in rats.Methods NP models were established in 32 SD rats by sciatic nerve ligation,and they were randomly divided into model group,low-and high-dose protocatechuic acid groups,and ibuprofen group(n=8);on the 3rd d of modeling,rats in the latter 3 groups were given 10 or 20 mg/kg protocatechuic acid solution via jugular vein injection or 20 mg/kg ibuprofen tablets by gavage,once a d for consecutive 21 d.A sham-operated group(n=8)was set up;the sciatic nerve was dissociated but not ligated.The behavioral performance of rats in each group was continuously observed;on the 7th,14th and 21st d of administration,the mechanical pain threshold of both hind limbs of rats was measured by von-Frey filament stimulation and the thermal pain threshold was measured by BME-410A thermal pain stimulator.Then,rats were sacrificed.The serum levels of tumor necrosis factorα(TNF-α)and interleukin-1β(IL-1β)were detected by ELISA.Cell apoptosis in the spinal cord tissues was observed by TUNEL.Western blotting was used to detect the expressions of nuclear factor-κB(NF-κB)/NOD-like receptor pyrin domain-related protein 3(NLRP3)signaling pathway related proteins in the spinal cord tissues.Results On the 7th,14th,and 21st d of administration,the thermal pain threshold and mechanical pain threshold in the model group were significantly decreased as compared with those in the sham-operated group(P<0.05);as compared with those in the model group,those in the low-and high-dose protocatechuic acid groups and ibuprofen group were significantly increased(P<0.05);as compared with those in the low-dose protocatechuic acid group,those in the high-dose protocatechuic acid group and ibuprofen group were significantly increased(P<0.05);those in the ibuprofen group were significantly increased as compared with those in the high-dose protocatechuic acid group(P<0.05).(2)On the 21st d of administration,as compared with those in sham-operated gro

关 键 词：原儿茶酸 核转录因子-ΚB NOD样受体热蛋白结构域相关蛋白3 慢性神经病理性疼痛 

分 类 号：R741[医药卫生—神经病学与精神病学]