Sigma-1受体在神经病理性疼痛大鼠内质网应激中的作用

doi:10.11958/20221491

天津医药 ›› 2023, Vol. 51 ›› Issue (4): 366-370.doi: 10.11958/20221491

Sigma-1受体在神经病理性疼痛大鼠内质网应激中的作用

莫少娥(), 刘可鹏, 傅文, 谢酬勤, 郁冬玲, 陈实, 蓝雨雁()

广西医科大学第一附属医院麻醉科（邮编530021）

收稿日期:2022-09-15 修回日期:2022-10-28 出版日期:2023-04-15 发布日期:2023-04-20
通讯作者: 蓝雨雁 E-mail:1137277517@qq.com;blueyuyan@163.com
作者简介:莫少娥（1995），女，硕士在读，主要从事神经病理性疼痛机制方面研究。E-mail：1137277517@qq.com
基金资助:
广西自然科学基金(2018GXNSFAA281101);广西研究生教育创新计划项目(YCSW2021120);广西医疗卫生适宜技术开发与推广应用项目(S2019109)

The role of sigma-1 receptor in endoplasmic reticulum stress in neuropathic pain rats

MO Shaoe(), LIU Kepeng, FU Wen, XIE Chouqin, YU Dongling, CHEN Shi, LAN Yuyan()

Department of Anesthesiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

Received:2022-09-15 Revised:2022-10-28 Published:2023-04-15 Online:2023-04-20
Contact: LAN Yuyan E-mail:1137277517@qq.com;blueyuyan@163.com

莫少娥, 刘可鹏, 傅文, 谢酬勤, 郁冬玲, 陈实, 蓝雨雁. Sigma-1受体在神经病理性疼痛大鼠内质网应激中的作用[J]. 天津医药, 2023, 51(4): 366-370.

MO Shaoe, LIU Kepeng, FU Wen, XIE Chouqin, YU Dongling, CHEN Shi, LAN Yuyan. The role of sigma-1 receptor in endoplasmic reticulum stress in neuropathic pain rats[J]. Tianjin Medical Journal, 2023, 51(4): 366-370.

摘要/Abstract

摘要：

目的探讨sigma-1受体（sig-1R）对神经病理性疼痛（NP）大鼠内质网应激的作用。方法将鞘内置管成功的SPF级雄性SD大鼠24只按随机数字表法分为假手术组（S组）、NP模型组（C组）、sig-1R抑制剂BD1047干预组（B组），每组8只。C组和B组采用坐骨神经慢性挤压性损伤法建立NP模型。术后第4、5、6天，S组和C组鞘内注射生理盐水20 μL，B组鞘内注射BD1047（120 μmol/L）20 μL，1次/d。于术前1 d及术后第1、3、5、7天检测术侧足机械缩足反应阈（MWT）。采用Westen blot和免疫荧光染色法检测背根神经元（DRG）sig-1R、免疫球蛋白重链结合蛋白（BIP）、转录活化因子4（ATF4）、C/EBP同源蛋白（CHOP）的表达情况；采用HE染色法观察DRG形态大小及病理改变；采用透射电镜观察DRG内质网改变。结果与S组比较，C组大鼠术后各时间点术侧足MWT明显下降，DRG病理损伤和内质网破坏明显加重，sig-1R、BIP、ATF4、CHOP表达均上调（P<0.05）；与C组比较，B组大鼠术后第5、7天MWT升高，DRG病理损伤和内质网破坏减轻，sig-1R、BIP、ATF4、CHOP表达均下调（P<0.05）。结论 sig-1R参与了大鼠神经病理性疼痛的过程，其机制可能与抑制DRG内质网应激有关。

关键词: 神经痛, 内质网应激, 免疫球蛋白重链, sigma-1受体, 背根神经元

Abstract:

Objective To investigate the role of sigma-1 receptor (sig-1R) in endoplasmic reticulum stress in neuropathic pain (NP) rats. Methods Twenty-four SPF male SD rats with successful sheath tube were divided into the sham operation group (group S), the neuropathic pain model group (group C) and the BD1047 intervention group (group B) according to random number table, with 8 rats in each group. Chronic crush injury of sciatic nerve was used to establish NP model. On the 4th, 5th and 6th day after operation, normal saline 20 μL was injected intrathecally in the group S and the group C, and BD1047 (120 μmol/L) 20 μL was injected intrathecally in the group B once a day. The mechanical foot withdrawal response threshold (MWT) of the surgical side foot was measured on the first day before operation and on the first, 3rd, 5th and 7th day after operation. Western blot assay and immunofluorescence staining were used to detect the expression levels of sig-1R, glucose-regulated protein (BIP), activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP) in dorsal root neurons (DRG). HE staining was used to observe the morphological size and pathological changes of DRG. Changes of endoplasmic reticulum in DRG were observed by scanning electron microscopy. Results Compared with the group S, intraoperative parapodum MWT was significantly decreased (P<0.05), and pathological injury and endoplasmic reticulum destruction of DRG were significantly aggravated. Expressions of sig-1R, BIP, ATF4 and CHOP were up-regulated in the group C after CCI (P<0.05). Compared with the group C, the MWT was increased on the 5th and 7th day after CCI in the group B (P<0.05), and the expressions of sig-1R, BIP, ATF4 and CHOP were down-regulated (P<0.05). The pathological injury of DRG was improved. Conclusion sig-1R are involved in the neuropathic pain in rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress in dorsal root neurons.

Key words: neuralgia, endoplasmic reticulum stress, immunoglobulin heavy chains, sigma-1 receptor, dorsal root neurons

中图分类号:

R614，R745

图/表 7

表1 3组大鼠不同时点MWT比较（n=8，g，$\bar{x} \pm s$）

Tab.1 Comparison of MWT at different time points between the three groups

组别	术前1 d	术后第1天	术后第3天	术后第5天	术后第7天
S组	18.5±6.4	17.1±5.7	17.8±7.0	17.7±5.0	18.7±8.1
C组	17.8±7.0	9.6±2.6^a	3.5±1.7^a	3.1±1.5^a	2.9±1.1^a
B组	17.1±5.7	9.2±1.4^a	3.4±1.5^a	7.0±1.5^ab	9.1±2.6^ab
F	0.092	11.267^**	30.215^**	44.659^**	20.159^**

图1 3组大鼠DRG组织中sig-1R、BIP、ATF4、CHOP蛋白Western blot条带

Fig.1 Western blot bands of sig-1R, BIP, ATF4 and CHOP in rat DRG of three groups

表2 3组大鼠DRG组织中sig-1R、BIP、ATF4、CHOP蛋白相对表达水平比较（n=8，$\bar{x} \pm s$）

Tab.2 Comparison of sig-1R, BIP, ATF4 and CHOP protein relative expression levels in DRG of rats between the three groups

组别	sig-1R	BIP	ATF4	CHOP
S组	0.281±0.094	0.396±0.112	0.421±0.046	0.341±0.063
C组	0.953±0.120^a	0.964±0.120^a	0.989±0.111^a	1.161±0.029^a
B组	0.726±0.043^ab	0.661±0.024^ab	0.744±0.068^ab	0.835±0.056^ab
F	41.625^**	26.319^**	37.754^**	189.762^**

表3 3组大鼠DRG组织sig-1R、BIP、ATF4、CHOP蛋白免疫荧光表达水平比较（n=8，$\bar{x} \pm s$）

Tab.3 Comparison of sig-1R, BIP, ATF4 and CHOP protein immunofluorescence expression levels in DRG of rats between the three groups

组别	sig-1R	BIP	ATF4	CHOP
S组	0.432±0.095	0.317±0.170	0.426±0.183	0.509±0.250
C组	9.001±1.362^a	7.324±1.040^a	4.751±1.640^a	5.866±2.305^a
B组	5.392±1.619^ab	2.508±0.615^ab	1.669±0.298^ab	1.524±0.271^ab
F	74.202^**	155.288^**	31.733^**	26.717^**

图2 各组大鼠DRG组织中sig-1R、BIP、ATF4、CHOP免疫荧光染色图（×200） sig-1R呈绿色，BIP、ATF4、CHOP呈红色，DAPI呈蓝色。

Fig.2 The sig-1R, BIP, ATF4 and CHOP immunofluorescence staining of DRG tissue in each group of rats (×200)

图3 各组大鼠DRG神经元形态学表现（HE染色，×400）

Fig.3 Morphological manifestations of DRG tissue in each group of rats (HE staining, ×400)

图4 各组大鼠DRG神经元内质网、线粒体表现（×3 000）

Fig.4 The expression of endoplasmic reticulum and mitochondria of DRG tissue in each group of rats (×3 000)

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Sigma-1受体在神经病理性疼痛大鼠内质网应激中的作用

The role of sigma-1 receptor in endoplasmic reticulum stress in neuropathic pain rats

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