马钱子苷抑制CXCL12/CXCR4信号通路对腰椎间盘突出症大鼠疼痛反应的影响

doi:10.11958/20230249

天津医药 ›› 2023, Vol. 51 ›› Issue (10): 1084-1089.doi: 10.11958/20230249

马钱子苷抑制CXCL12/CXCR4信号通路对腰椎间盘突出症大鼠疼痛反应的影响

乔松(), 胡艳平, 何生华^△()

武汉市中医医院推拿科（邮编430000）

收稿日期:2023-02-27 修回日期:2023-04-19 出版日期:2023-10-15 发布日期:2023-10-18
通讯作者: ^∆E-mail：gongcjz11@163.com
作者简介:乔松（1984），男，主治医师，主要从事针灸推拿康复治疗及各类疼痛性疾病方面研究。E-mail：qiaosong1984q@163.com
基金资助:
湖北省中医药管理局中医药科研项目(ZY2023M026)

Impact of loganin on pain response in rats with lumbar disc herniation by inhibiting CXCL12/CXCR4 signal pathway

QIAO Song(), HU Yanping, HE Shenghua^△()

Department of Massage, Wuhan Hospital of Traditional Chinese Medicine, Wuhan 430000, China

Received:2023-02-27 Revised:2023-04-19 Published:2023-10-15 Online:2023-10-18
Contact: ^∆E-mail：gongcjz11@163.com

乔松, 胡艳平, 何生华. 马钱子苷抑制CXCL12/CXCR4信号通路对腰椎间盘突出症大鼠疼痛反应的影响[J]. 天津医药, 2023, 51(10): 1084-1089.

QIAO Song, HU Yanping, HE Shenghua. Impact of loganin on pain response in rats with lumbar disc herniation by inhibiting CXCL12/CXCR4 signal pathway[J]. Tianjin Medical Journal, 2023, 51(10): 1084-1089.

摘要/Abstract

摘要：

目的探讨马钱子苷（loganin）调控CXC趋化因子配体（CXCL12）/CXC趋化因子受体4（CXCR4）信号通路对腰椎间盘突出症（LDH）模型大鼠疼痛反应的影响。方法将50只大鼠按随机数字表法抽取10只为假手术组（Sham组），其余大鼠建立LDH大鼠模型，将模型大鼠随机分为Model组、CXCR4拮抗剂组（AMD3100组，鞘内注射20 μg）、马钱子苷组（5 mg/kg，腹腔注射）、马钱子苷（5 mg/kg，腹腔注射）+CXCL12组（鞘内注射250 ng），每组10只。按照药物分组干预后，分别检测大鼠热撤足反应潜伏期与机械性撤足阈值，HE染色观察脊髓背角组织形态学变化，采用酶联免疫吸附试验检测脊髓背角组织肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6水平，免疫荧光染色检测小胶质细胞激活情况，Western blot检测CXCL12/CXCR4通路相关蛋白表达。结果与Sham组比较，Model组脊髓背角组织损伤严重，大鼠热撤足反应潜伏期、机械性撤足阈值降低，脊髓背角组织小胶质细胞及TNF-α、IL-1β、IL-6、CXCL12、CXCR4、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、胱天蛋白酶1（caspase-1）蛋白表达水平升高（P<0.05）；与Model组比较，AMD3100组与马钱子苷组脊髓背角组织病理损伤减轻，大鼠热撤足反应潜伏期、机械性撤足阈值升高，脊髓背角组织小胶质细胞及TNF-α、IL-1β、IL-6、CXCL12、CXCR4、NLRP3、caspase-1蛋白表达水平降低（P<0.05）；CXCL12可削弱马钱子苷对LDH大鼠疼痛反应的改善作用（P<0.05）。结论马钱子苷可改善LDH大鼠疼痛反应，可能与其抑制CXCL12/CXCR4信号通路活性有关。

关键词: 疼痛, 椎间盘移位, 马钱子苷, 趋化因子CXCL12, 受体, CXCR4

Abstract:

Objective To investigate the impact of loganin on pain response in rats with lumbar disc herniation (LDH) by regulating CXCL12/CXCR4 signal pathway. Methods Ten of the 50 rats were randomly selected as the sham group according to random number table method, and LDH rat model was established in other rats. Model rats were randomly divided into the model group, the CXCR4 antagonist group (AMD3100 group, intrathecal injection, 20 μg), the loganin group (5 mg/kg, intraperitoneal injection), and the loganin (5 mg/kg, intraperitoneal injection)+CXCL12 group (intrathecal injection, 250 ng), with 10 animals in each group. After the intervention according to drug groups, the latency of thermal foot withdrawal reaction and the threshold of mechanical foot withdrawal threshold were measured respectively. HE staining was applied to observe histomorphological changes of spinal dorsal horn. Levels of TNF-α, IL-1β and IL-6 in spinal dorsal horn were detected by ELISA. Immunofluorescence staining was applied to detect the activation of microglia. Western blot assay was used to detect the level of CXCL12/CXCR4 pathway related proteins. Results Compared with the sham group, the model group had severe spinal cord dorsal horn tissue injury, the latency of thermal foot withdrawal reaction and mechanical foot withdrawal threshold were lower, and levels of microglia, levels of TNF-α, IL-1β, IL-6, and protein expression levels of CXCL12, CXCR4, NLRP3, caspase-1 and IL-1β in spinal dorsal horn tissue were higher (P<0.05). Compared with the model group, the pathological injury of spinal dorsal horn tissue was reduced in the AMD3100 group and the loganin group. The latency of thermal foot withdrawal reaction and mechanical foot withdrawal threshold were higher, and levels of microglia, levels of TNF-α, IL-1β, IL-6, and the protein expression levels of CXCL12, CXCR4, NLRP3, caspase-1 and IL-1β in the spinal dorsal horn tissue were also lower (P<0.05). CXCL12 could weaken the improvement effect of loganin on pain response in LDH rats (P<0.05). Conclusion Loganin can improve the pain response of LDH rats, which may be related to the inhibition of CXCL12/CXCR4 signal pathway.

Key words: pain, intervertebral disc displacement, loganin, chemokine CXCL12, receptors, CXCR4

中图分类号:

R285.5

图/表 7

参考文献 18

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组别	建模后1 d	治疗后3 d	治疗后7 d	治疗后14 d
Sham组	16.21±1.47	17.27±1.54	17.36±1.63	16.89±1.74
Model组	8.31±1.22^a	7.54±1.03^a	7.36±1.12^a	7.98±1.05^a
AMD3100组	8.42±1.21^a	9.15±0.87^b	10.23±1.15^b	12.32±1.26^b
马钱子苷组	8.56±1.16^a	9.23±0.98^b	10.45±1.02^b	13.02±1.61^b
马钱子苷+ CXCL12组	7.87±0.96^a	8.05±0.74	8.32±0.62^c	10.14±1.10^c
F	85.440^＊＊	139.789^＊＊	115.357^＊＊	58.628^＊＊

组别	建模后1 d	治疗后3 d	治疗后7 d	治疗后14 d
Sham组	16.21±1.47	17.27±1.54	17.36±1.63	16.89±1.74
Model组	8.31±1.22^a	7.54±1.03^a	7.36±1.12^a	7.98±1.05^a
AMD3100组	8.42±1.21^a	9.15±0.87^b	10.23±1.15^b	12.32±1.26^b
马钱子苷组	8.56±1.16^a	9.23±0.98^b	10.45±1.02^b	13.02±1.61^b
马钱子苷+ CXCL12组	7.87±0.96^a	8.05±0.74	8.32±0.62^c	10.14±1.10^c
F	85.440^＊＊	139.789^＊＊	115.357^＊＊	58.628^＊＊

组别	建模后1 d	治疗后3 d	治疗后7 d	治疗后14 d
Sham组	27.45±1.48	28.15±1.56	28.54±1.67	28.74±1.83
Model组	10.56±0.83^a	10.24±0.91^a	11.15±1.06^a	11.34±1.42^a
AMD3100组	10.72±0.78^a	13.26±0.84^b	17.64±1.32^b	22.56±1.93^b
马钱子苷组	10.89±0.90^a	13.58±0.87^b	18.25±1.43^b	23.43±2.12^b
马钱子苷+ CXCL12组	10.31±0.72^a	12.29±0.76	13.60±1.05^c	15.23±1.34^c
F	588.603^＊＊	487.330^＊＊	251.968^＊＊	156.140^＊＊

组别	建模后1 d	治疗后3 d	治疗后7 d	治疗后14 d
Sham组	27.45±1.48	28.15±1.56	28.54±1.67	28.74±1.83
Model组	10.56±0.83^a	10.24±0.91^a	11.15±1.06^a	11.34±1.42^a
AMD3100组	10.72±0.78^a	13.26±0.84^b	17.64±1.32^b	22.56±1.93^b
马钱子苷组	10.89±0.90^a	13.58±0.87^b	18.25±1.43^b	23.43±2.12^b
马钱子苷+ CXCL12组	10.31±0.72^a	12.29±0.76	13.60±1.05^c	15.23±1.34^c
F	588.603^＊＊	487.330^＊＊	251.968^＊＊	156.140^＊＊

组别	TNF-α	IL-1β	IL-6
Sham组	95.24±10.21	56.43±8.34	35.34±5.61
Model组	274.36±42.31^a	149.54±12.42^a	185.42±32.41^a
AMD3100组	132.46±16.55^b	92.35±8.75^b	65.33±7.32^b
马钱子苷组	127.48±15.28^b	95.36±9.82^b	70.25±8.14^b
马钱子苷+ CXCL12组	183.14±20.42^c	112.47±10.23^c	131.46±12.45^c
F	86.880^＊＊	114.180^＊＊	133.820^＊＊

马钱子苷抑制CXCL12/CXCR4信号通路对腰椎间盘突出症大鼠疼痛反应的影响

Impact of loganin on pain response in rats with lumbar disc herniation by inhibiting CXCL12/CXCR4 signal pathway

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组别		CXCL12		CXCR4
Sham组		0.25±0.04		0.19±0.03
Model组		0.95±0.08^a		1.15±0.12^a
AMD3100组		0.43±0.05^b		0.61±0.07^b
马钱子苷组		0.45±0.06^b		0.63±0.08^b
马钱子苷+CXCL12组		0.73±0.07^c		0.85±0.09^c
F		100.684^＊＊		89.539^＊＊
组别	NLRP3		caspase-1		IL-1β
Sham组	0.32±0.05		0.15±0.03		0.21±0.05
Model组	1.24±0.13^a		1.03±0.12^a		0.97±0.08^a
AMD3100组	0.56±0.06^b		0.29±0.04^b		0.35±0.04^b
马钱子苷组	0.53±0.07^b		0.27±0.05^b		0.34±0.05^b
马钱子苷+CXCL12组	1.01±0.10^c		0.57±0.06^c		0.66±0.07^c
F	94.901^＊＊		135.348^＊＊		132.165^＊＊

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