首页|壮医经筋推拿对神经病理性疼痛大鼠去泛素化酶BRCC3介导NLRP3去泛素化修饰的影响及镇痛机制

壮医经筋推拿对神经病理性疼痛大鼠去泛素化酶BRCC3介导NLRP3去泛素化修饰的影响及镇痛机制

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目的 探讨壮医经筋推拿对神经病理性疼痛大鼠去泛素化酶BRCC3 介导NOD样受体家族热蛋白结构域相关蛋白3(NLRP3)去泛素化修饰的影响及其镇痛分子学机制。方法 将45 只雌性SD大鼠随机分为5 组，每组9 只。模型组、假手术组、壮医经筋推拿组采用L5 脊神经结扎的方法建立神经病理性疼痛模型。于术后第1 天开始，假推拿组对大鼠双侧后肢进行轻轻抚摸，壮医经筋推拿组采用按摩推拿手法模拟仪刺激大鼠脊神经结扎节段相应体表部位及所结扎神经支配区域并进行推拿，连续干预14 d;其余3 组不予干预，观察14 d。于术前及术后1 d、3 d、14 d测定各组大鼠机械性痛觉阈值和热痛觉阈值;术后14 d，采用qPCR技术检测脊髓背角中BRCC3 和NL-RP3 mRNA表达情况，采用ELISA法检测血清白细胞介素-1β(IL-1β)水平。结果 术后1d、3d，各手术组大鼠的机械性痛觉阈值和热痛觉阈值均明显低于正常组(P均＜0。05);术后14 d，壮医经筋推拿组大鼠的机械性痛觉阈值和热痛觉阈值均明显高于模型组和假推拿组(P均＜0。05)。术后14 d，模型组和假推拿组大鼠脊髓背角中BRCC3、NLRP3mRNA相对表达量及血清IL-1β水平均明显高于正常组(P均＜0。05)，壮医经筋推拿组大鼠脊髓背角中BRCC3、NLRP3mRNA相对表达量及血清IL-1β水平均明显低于模型组和假推拿组(P均＜0。05)。结论 壮医经筋推拿可减轻神经病理性疼痛大鼠痛敏反应，其机制与下调脊髓背角中去泛素化酶BRCC3 表达，以抑制NL-RP3 的去泛素化修饰，从而阻止NLRP3 的活化，阻碍IL-1β成熟和分泌，阻断其介导的免疫炎症反应有关。
Effect of muscle regions massage of Zhuang medicine on de-ubiquitination modification of NLRP3 mediated by BRCC3 in neuropathic pain rats and its analgesic mechanism
Objective It is to investigate the effect of muscle regions massage of Zhuang medicine on the de-ubiquitina-tion modification of Nod-like receptor protein 3(NLRP3)mediated by de-ubiquitinating enzyme BRCC3 in rats with neuro-pathic pain(NPP)and its molecular mechanism of analgesia.Methods Forty-five female SPF grade SD rats were randomly divided into 5 groups:model group,normal group,group of muscle regions massage of Zhuang medicine,sham massage group and sham operation group,with 9 rats in each group.The models of NPP were established by L5 spinal nerve ligation in the model group,group of muscle regions massage of Zhuang medicine and sham operation group.Beginning on the first postoperative day,the rats of the sham massage group were gently stroked on the bilateral hind limbs,and the rats of the group of muscle regions massage of Zhuang medicine were treated with a massage acupressure manipulation simulator to stimulate the corresponding body surface parts of the spinal nerve ligated segments and the innervation areas of the ligated nerves and with massage,continuously treated for 14 days,while the remaining three groups were given no intervention and were observed for 14 days.The mechanical pain threshold and heat pain threshold of rats in each group were measured be-fore operation and at 1,3,and 14 days after operation;at 14 days after operation,the expressions of BRCC3 and NLRP3 mRNA in the dorsal horn of the L4-6 spinal cord were detected by qPCR,and the serum level of interleukin-1β(IL-1β)was detected by ELISA.Results At 1 and 3 days after operation,the mechanical pain threshold and heat pain threshold of rats in each surgical group were significantly lower than those in the normal group(all P＜0.05);at 14 days after opera-tion,the mechanical pain threshold and heat pain threshold of rats in the group of muscle regions massage of Zhuang medi-cine were significantly higher than those in the model group and sham massage group(all P＜0.05).At14 days after op-eration,the relative expressions of BRCC3 and NLRP3 mRNA in dorsal horn of spinal cord and levels of IL-1β in serum of rats in the model group and sham massage group were significantly higher than those in the normal group(all P＜0.05),and the relative expressions of BRCC3 and NLRP3 mRNA in dorsal horn of spinal cord and levels of IL-1β in serum of rats in the group of muscle regions massage of Zhuang medicine were significantly lower than those in the model group and sham massage group(all P＜0.05).Conclusion Muscle regions massage of Zhuang medicine can reduce the pain sensitivity of rats with neuropathic pain,and its mechanism is related to the down-regulation of the expression of the de-ubiquitination en-zyme BRCC3 in the dorsal horn of spinal cord,so as to inhibit the de-ubiquitination modification of NLRP3,thus to reduce the activation of NLRP3 and block maturity and secretion of IL-1β to block its mediated immune inflammatory reaction.

muscle regions massage of Zhuang medicineneuropathic painubiquitinationIL-1βNLRP3

王天翊、唐宏亮、梁英业、庞军、卢栋明、唐业妮、郑玉娇、何育风

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广西中医药大学,广西 南宁 530000

防城港市中医医院,广西 防城港 538000

广西中医药大学第一附属医院,广西 南宁 530000

壮医经筋推拿 神经病理性疼痛 泛素化 白细胞介素-1β NLRP3

广西自然科学基金项目广西自然科学基金项目国家自然科学基金资助项目国家自然科学基金资助项目国家自然科学基金资助项目国家自然科学基金资助项目

2023GXNSFDA0260122020GXNSFBA29705382205305820745748216094382260976

2024

10.3969/j.issn.1008-8849.2024.01.003

现代中西医结合杂志
中国中西医结合学会河北分会,中华中医药学会

现代中西医结合杂志

CSTPCD
影响因子：1.775
ISSN：1008-8849
年,卷(期)：2024.33(1)
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