| 益肾养髓方对退行性颈脊髓病大鼠脊髓组织细胞焦亡的影响 |
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投稿时间：2025-01-16
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| 作者 | Author | 单位 | Address | E-Mail |
| 马国梁 |
MA Guo-liang |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
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| 银河 |
YIN He |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
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| 许博 |
XU Bo |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
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| 冯敏山 |
FENG Min-shan |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
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| 张丹 |
ZHANG Dan |
清华大学生物医学测试中心共享仪器平台, 北京 100804 |
Shared Instrument Platform of Biomedical Testing Center, Tsinghua University, Beijing 100804, China |
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| 张典 |
ZHANG Dian |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
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| 秦晓宽 |
QIN Xiao-kuan |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
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| 朱立国 |
ZHU Li-guo |
中国中医科学院望京医院, 北京 100102
中医正骨技术北京市重点实验室, 北京 100700 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China
Beijing Key Laboratory of Bone Setting Technology of Traditional Chinese Medicine, Beijing 100700, China |
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| 杨博文 |
YANG Bo-wen |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
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| 陈忻 |
CHEN Xin |
中国中医科学院望京医院, 北京 100102 |
Wangjing Hospital, China Academy of Traditional Chinese Medicine, Beijing 100102, China |
15101161150@139.com |
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| 期刊信息：《中国骨伤》2025年，第25卷，第5期，第532-539页 |
| DOI：10.12200/j.issn.1003-0034.20240880 |
| 基金项目: |
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中文摘要:
目的:初步探讨益肾养髓方对退行性颈脊髓病大鼠神经功能恢复的影响及作用机制。
方法:采用随机数字表法将50只成年SD雌性大鼠随机分为空白组、假手术组、模型组、益肾养髓方组和阳性药物组。模型组,益肾养髓方组和阳性药物组大鼠采用聚乙烯醇丙烯酰胺互穿网络水凝胶(吸水膨胀材料)构建大鼠脊髓慢性压迫模型。假手术组植入吸水膨胀材料后即取出,不造成脊髓压迫。其中空白组、假手术组和模型组予等量生理盐水灌胃,益肾养髓方组予中药汤剂灌胃(每天9.1 g·kg-1),阳性药物组予单唾液酸四己糖神经节苷脂钠腹腔注射(每天4.2 mg·kg-1)。在给药1、3、7、14 d后通过BBB法对大鼠的运动功能进行评估。给药14 d后处死大鼠取脊髓组织,通过HE染色观察脊髓受压部位形态学变化,并通过Western Blot法检测脊髓损伤区域内Caspase-1、GSDMD、NLRP3、PYCARD、白细胞介素(interleuk,IL)-1β、IL-18的表达水平。
结果:造模后空白组与假手术组各时间点的 Basso Beatlie Bresnahan(BBB)评分均正常,且均高于模型组、益肾养髓方组、阳性药物组BBB评分,差异均有统计学意义(P<0.05)。自灌药后第3天起,在各个时间点,益肾养髓方组与阳性药物组大鼠BBB评分均高于模型组大鼠,差异均有统计学意义(P<0.05)。空白组与假手术组HE脊髓组织染色形态正常,模型组HE脊髓损伤严重,神经元大量死亡,益肾养髓方组与阳性药物组脊髓与神经细胞损伤减轻。模型组大鼠脊髓中焦亡相关蛋白Caspase-1、GSDMD、NLRP3、PYCARD、IL-1β、IL-18的表达水平均显著高于假手术组,差异均有统计学意义(P<0.000 1),益肾养髓方组和阳性药物组焦亡蛋白的表达均低于模型组,差异均有统计学意义(P<0.05)。
结论:益肾养髓方可改善退行性颈脊髓病大鼠的运动功能,减轻病理变化,促进脊髓神经功能的恢复。其具体机制可能与抑制炎症小体NLRP3、PYCARD的活化,减少炎症因子IL-1β、IL-18的释放,降低焦亡相关蛋白Caspase-1、GSDMD的表达,减轻细胞焦亡,抑制炎症反应有关。 |
| 【关键词】益肾养髓方 脊髓损伤 细胞焦亡 炎症反应 大鼠 |
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| Effects of Yishen Yangsui formula(益肾养髓方) on pyroptosis in the spinal cord tissue in rats with degenerative cervical myelopathy |
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ABSTRACT
Objective To preliminarily investigate the effects and mechanism of action of Yishen Yangsui Formula (益肾养髓方,YSYSF)on the recovery of neurological function in rats with degenerative cervical myelopathy.
Methods Fifty adult SD female rats were randomly divided into control group,sham group,model group,YSYSF group and positive drug group by using randomized numerical table method. In the model group,YSYSF group and positive drug group,polyvinyl alcohol acrylamide interpenetrating network hydrogel(water-absorbent swelling material) was used to construct a rat spinal cord chronic compression model. The sham group was implanted with the water-absorbent swelling material and then removed without causing spinal cord compression. The control group,the sham group and the model group were given equal amounts of saline by gavage,the group of YSYSF was given Chinese herbal medicine soup by gavage 9.1 g·kg-1 once a day,and the positive drug group was given tetrahexylsalicylglucoside sodium monosialate ganglioside by intraperitoneal injection 4.2 mg·kg-1 once a day. The motor function of the rats was assessed by the BBB method after 1,3,7,and 14 d of drug administration. The spinal cord tissues were taken from rats executed 14 d after drug administration,and the morphological changes of the spinal cord compression site were observed by HE staining,and the expression levels of Caspase-1,GSDMD,NLRP3,PYCARD,IL-1β,and IL-18 were detected in the area of spinal cord injury by Western blot method.
Results The BBB scores of the control group and the sham group were normal at all time points after modeling,which were higher than the BBB scores of the model group,the YSYSF,and the positive drug group (P<0.05). From the 3rd day after gavage,at all time points,the BBB scores of rats in the YSYSF group and the positive drug group were higher than those of rats in the model group (P<0.05). The staining pattern of HE spinal cord tissue was normal in the control group and the sham group,and the HE spinal cord in the model group was severely damaged with a large number of neuron deaths,whereas the damage to the spinal cord and neuron cells was reduced in the YSYSF group and the positive drug group. The expression levels of caspase-1,GSDMD,NLRP3,PYCARD,IL-1β and IL-18 in the spinal cord of the model group were significantly higher than those of the sham group (P<0.0001),and the expression levels of caspase-1,GSDMD,NLRP3,PYCARD,IL-1β,and IL-18 in the YSYSF group and the drug group were significantly lower than those in the model group (P<0.05).
Conclusion YSYSF can improve the motor function of rats with degenerative cervical spinal cord disease,alleviate the pathological changes,and promote the recovery of spinal cord neurological function. The specific mechanism may be related to the inhibition of the activation of inflammatory vesicles NLRP3 and PYCARD,the reduction of the release of inflammatory factors IL-1β and IL-18,the reduction of the expression of caspase-1 and GSDMD,the reduction of cellular death,and the inhibition of inflammatory response. |
| KEY WORDS Yishen Yangsui formula Spinal cord injury Pyroptosis Inflammatory response Rats |
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| 引用本文，请按以下格式著录参考文献： |
| 中文格式: | 马国梁,银河,许博,冯敏山,张丹,张典,秦晓宽,朱立国,杨博文,陈忻.益肾养髓方对退行性颈脊髓病大鼠脊髓组织细胞焦亡的影响[J].中国骨伤,2025,25(5):532~539 |
| 英文格式: | MA Guo-liang,YIN He,XU Bo,FENG Min-shan,ZHANG Dan,ZHANG Dian,QIN Xiao-kuan,ZHU Li-guo,YANG Bo-wen,CHEN Xin.Effects of Yishen Yangsui formula(益肾养髓方) on pyroptosis in the spinal cord tissue in rats with degenerative cervical myelopathy[J].zhongguo gu shang / China J Orthop Trauma ,2025,25(5):532~539 |
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