七氟醚调节ROS/TXNIP/NLRP3通路对脊髓损伤大鼠神经细胞炎症的影响

doi:10.11958/20251781

天津医药 ›› 2025, Vol. 53 ›› Issue (9): 910-915.doi: 10.11958/20251781

七氟醚调节ROS/TXNIP/NLRP3通路对脊髓损伤大鼠神经细胞炎症的影响

周玉科(), 孙伟, 高庆, 贺军^△()

成都市第七人民医院新南院区骨科（邮编610021）

收稿日期:2025-04-29 修回日期:2025-06-17 出版日期:2025-09-15 发布日期:2025-09-16
通讯作者: ^△E-mail：171748812@qq.com
作者简介:周玉科（1983），男，副主任医师，主要从事脊柱外科基础实验方面研究。E-mail：vd5659@sina.com
基金资助:
四川省医学科研课题计划项目(S21088)

The effect of sevoflurane on neuronal inflammation in rats with spinal cord injury by regulating the ROS/TXNIP/NLRP3 pathway

ZHOU Yuke(), SUN Wei, GAO Qing, HE Jun^△()

Department of Orthopedics, New South Campus of Chengdu Seventh People's Hospital, Chengdu 610021, China

Received:2025-04-29 Revised:2025-06-17 Published:2025-09-15 Online:2025-09-16
Contact: ^△E-mail: 171748812@qq.com

周玉科, 孙伟, 高庆, 贺军. 七氟醚调节ROS/TXNIP/NLRP3通路对脊髓损伤大鼠神经细胞炎症的影响[J]. 天津医药, 2025, 53(9): 910-915.

ZHOU Yuke, SUN Wei, GAO Qing, HE Jun. The effect of sevoflurane on neuronal inflammation in rats with spinal cord injury by regulating the ROS/TXNIP/NLRP3 pathway[J]. Tianjin Medical Journal, 2025, 53(9): 910-915.

摘要/Abstract

摘要：

目的探讨七氟醚通过调节活性氧（ROS）/硫氧还蛋白相互作用蛋白（TXNIP）/核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）通路对脊髓损伤大鼠神经细胞炎症的影响。方法 72只大鼠以随机数字表法分为模型组（构建脊髓损伤模型），假手术组，低、中、高浓度（分别为1%、2%、4%七氟醚）七氟醚组，联合组（4%七氟醚+3.7 mg/kg ROS激活剂三甲胺N-氧化物），每组12只。脊髓损伤行为学（BBB）评分、足迹印记试验评价运动功能；酶联免疫吸附试验（ELISA）检测脊髓组织白细胞介素（IL）-18、肿瘤坏死因子-α（TNF-α）、IL-1β水平；HE染色观察脊髓组织病理变化；TUNEL检测细胞凋亡；qRT-RCR检测TXNIP、NLRP3 mRNA表达；ROS试剂盒检测ROS活性；Western blot检测ROS/TXNIP/NLRP3通路蛋白表达。结果假手术组步态、细胞形态正常、排列有序，脊髓结构完好；模型组有脚趾拖动、脊髓组织损伤严重，炎性细胞浸润；模型组较假手术组BBB评分降低，IL-18、TNF-α、IL-1β水平、凋亡率、ROS活性升高，TXNIP和NLRP3 mRNA及蛋白表达升高（P<0.05）；低、中、高浓度七氟醚组较模型组上述指标改善；联合组则反转高浓度七氟醚组的改善结果。结论七氟醚可能通过抑制ROS/TXNIP/NLRP3通路减轻脊髓损伤大鼠神经细胞炎症。

关键词: 七氟醚, 脊髓损伤, 活性氧, 硫氧还蛋白质类, NLR家族, 热蛋白结构域包含蛋白3, 神经元, 炎症

Abstract:

Objective To investigate the effect of sevoflurane on neuroinflammation in rats with spinal cord injury by regulating the reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway. Methods Seventy-two rats were randomly divided into six groups using a random number table method, with 12 rats in each group: the model group (establishing the rat model of spinal cord injury), the sham operation group, the low-, medium- and high-concentration sevoflurane groups (1%, 2% and 4% sevoflurane, respectively) and the combination group (4% sevoflurane + 3.7 mg/kg reactive oxygen species (ROS) activator trimethylamine N-oxide). Spinal cord injury behavior (BBB) score and footprint imprint test were used to evaluate motor function. ELISA method was used to detect the levels of IL-18, TNF-α and IL-1β in spinal cord tissue. HE staining was used to detect pathological changes in spinal cord tissue. TUNEL method was used to detect cell apoptosis. In addition, the expression of TXNIP and NLRP3 mRNA were detected by qRT-PCR. ROS activity was detected by ROS kit. Western blot assay was used to detect the expression of ROS/TXNIP/NLRP3 pathway proteins. Results The sham operation group showed normal gait, normal cell morphology with orderly arrangement and intact spinal cord structure. The model group presented with toe dragging, severe spinal cord tissue injury and inflammatory cell infiltration. The BBB score was lower in the model group compared to that of the sham surgery group, while IL-18, TNF-α, IL-1β levels, apoptosis rate, ROS activity, TXNIP, NLRP3 mRNA and protein expression were increased (P<0.05). The above indexes were improved in the low-concentration, medium-concentration and high-concentration sevoflurane groups compared with those in the model group. However, the combined group reversed the improvement results of the high-concentration sevoflurane group. Conclusion Sevoflurane can alleviate neuroinflammation in rats with spinal cord injury by inhibiting the ROS/TXNIP/NLRP3 pathway.

Key words: sevoflurane, spinal cord injuries, reactive oxygen species, thioredoxins, NLR family, pyrin domain-containing 3 protein, neurons, inflammation

中图分类号:

R651.2

图/表 9

参考文献 25

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基因名称	引物序列（5′→3′）	产物大小/bp
TXNIP	上游：CCGAGCCAGCCAACTCAAGA	189
TXNIP	下游：AGACAGACACCCGCCCATCA	189
NLRP3	上游：GAATTAGACAACTGCAACCTCACG	195
NLRP3	下游：GTTTCAGCACTTCACAGAACATCAT	195
GAPDH	上游：GGTGGTCTCCTCTGACTTCAA	178
GAPDH	下游：GTTGCTGTAGCCAAATTCGTTGT	178

基因名称	引物序列（5′→3′）	产物大小/bp
TXNIP	上游：CCGAGCCAGCCAACTCAAGA	189
TXNIP	下游：AGACAGACACCCGCCCATCA	189
NLRP3	上游：GAATTAGACAACTGCAACCTCACG	195
NLRP3	下游：GTTTCAGCACTTCACAGAACATCAT	195
GAPDH	上游：GGTGGTCTCCTCTGACTTCAA	178
GAPDH	下游：GTTGCTGTAGCCAAATTCGTTGT	178

组别	BBB评分
组别	第7天	第14天
假手术组	21.00±0.00	21.00±0.00
模型组	5.23±0.57^a	6.89±0.69^a
低浓度七氟醚组	6.59±0.66^b	8.53±0.87^b
中浓度七氟醚组	7.92±0.81^bc	10.05±1.12^bc
高浓度七氟醚组	9.25±0.93^bcd	11.86±1.26^bcd
联合组	6.15±0.62^e	7.62±0.79^e
F	932.357^＊＊	416.942^＊＊

组别	BBB评分
组别	第7天	第14天
假手术组	21.00±0.00	21.00±0.00
模型组	5.23±0.57^a	6.89±0.69^a
低浓度七氟醚组	6.59±0.66^b	8.53±0.87^b
中浓度七氟醚组	7.92±0.81^bc	10.05±1.12^bc
高浓度七氟醚组	9.25±0.93^bcd	11.86±1.26^bcd
联合组	6.15±0.62^e	7.62±0.79^e
F	932.357^＊＊	416.942^＊＊

组别	IL-18/（ng/L）	TNF-α/（μg/L）	IL-1β/（ng/L）
假手术组	61.28±6.25	6.58±0.67	101.27±10.35
模型组	151.32±15.27^a	18.32±1.91^a	195.37±20.17^a
低浓度七氟醚组	121.65±12.33^b	15.47±1.63^b	167.83±17.14^b
中浓度七氟醚组	104.57±11.57^bc	12.56±1.27^bc	136.42±13.82^bc
高浓度七氟醚组	85.66±8.72^bcd	9.36±0.95^bcd	119.67±12.17^bcd
联合组	139.58±14.05^e	16.89±1.72^e	178.69±17.92^e
F	49.446^＊＊	61.216^＊＊	32.756^＊＊

七氟醚调节ROS/TXNIP/NLRP3通路对脊髓损伤大鼠神经细胞炎症的影响

The effect of sevoflurane on neuronal inflammation in rats with spinal cord injury by regulating the ROS/TXNIP/NLRP3 pathway

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参考文献 25

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组别	细胞凋亡率/%	TXNIP mRNA	NLRP3 mRNA
假手术组	1.83±0.19	0.98±0.11	1.02±0.12
模型组	32.17±3.36^a	1.87±0.21^a	2.07±0.23^a
低浓度七氟醚组	23.36±2.46^b	1.62±0.19^b	1.75±0.19^b
中浓度七氟醚组	15.28±1.68^bc	1.46±0.16^bc	1.52±0.17^bc
高浓度七氟醚组	7.66±0.79^bcd	1.21±0.13^bcd	1.25±0.14^bcd
联合组	25.13±2.63^e	1.73±0.18^e	1.86±0.20^e
F	170.013^＊＊	24.007^＊＊	29.021^＊＊

组别	ROS活性/（U/mL）	TXNIP/GAPDH	NLRP3/GAPDH
假手术组	142.36±14.63	0.86±0.09	1.12±0.12
模型组	236.75±24.17^a	2.24±0.23^a	2.69±0.27^a
低浓度七氟醚组	211.73±22.63^b	1.82±0.19^b	2.35±0.24^b
中浓度七氟醚组	182.65±18.59^bc	1.39±0.14^bc	1.78±0.18^bc
高浓度七氟醚组	156.39±16.24^bcd	0.97±0.10^bcd	1.25±0.13^bcd
联合组	220.58±22.77^e	2.03±0.21^e	2.43±0.25^e
F	20.754^＊＊	68.184^＊＊	60.156^＊＊

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