文章摘要
汪逸纯,万贵平,张真真.基于COX-2/PGE2信号通路探讨温肾消癥汤减轻子宫内膜异位症小鼠疼痛的作用机制[J].浙江中医药大学学报,2024,48(10):1199-1208.
基于COX-2/PGE2信号通路探讨温肾消癥汤减轻子宫内膜异位症小鼠疼痛的作用机制
Mechanism of Wenshen Xiaozheng Decoction Relieving Pain in Endometriosis Mouse Model Based on COX-2/PGE2 Signaling Pathway
DOI:10.16466/j.issn1005-5509.2024.10.002
中文关键词: 子宫内膜异位症  疼痛  COX-2  PGE2  中枢敏化  外周敏化
英文关键词: endometriosis  pain  COX-2  PGE2  central sensitization  peripheral sensitization
基金项目:国家自然科学基金项目(82074319、82174420);江苏省中医药研究院自主科研项目(BM2018024-2019007)
作者单位
汪逸纯 南京中医药大学附属中西医结合医院 南京 210028
江苏省中医药研究院
温州医科大学附属台州市妇女儿童医院 
万贵平 南京中医药大学附属中西医结合医院 南京 210028
江苏省中医药研究院 
张真真 南京中医药大学附属中西医结合医院 南京 210028
江苏省中医药研究院 
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中文摘要:
      [目的] 基于环氧合酶-2/前列腺素E2 (cyclooxyfenase-2/prostaglandin E2, COX-2/PGE2)信号通路,探讨温肾消癥汤对子宫内膜异位症(endometriosis,EMS)模型小鼠疼痛的影响及其作用机制。[方法] 采用腹腔注射法建立EMS小鼠模型40只作为造模组,并随机将造模组分为EMS模型组(0.2 mL无菌蒸馏水)、温肾消癥汤组(0.2 mL温肾消癥汤浓缩液)、阳性对照组(0.2 mL阿司匹林混悬液),其他10只小鼠设为假手术组。造模21 d中,以Von Frey纤维丝实验与热板实验检测造模组与假手术组小鼠机械疼痛与热敏疼痛阈值。给药的21 d中,以Von Frey纤维丝实验与热板实验检测EMS模型组、温肾消癥汤组、阳性对照组小鼠机械疼痛与热敏疼痛阈值。给药21 d后,每天阴道涂片确定小鼠动情周期。在同一动情周期处死小鼠,并留取血清,腹腔冲洗液(peritoneal fluid,PF),内膜组织(在位、异位),丘脑,脊髓,背根神经节(dorsal root ganglion,DRG)。以酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)测定各样本中COX-2、PGE2、瞬时电位受体V1(transient receptor potential vanilloid 1,TRPV1)、钠电压门控通道α亚基11(sodium channel protein type 11 subunit alpha, SCN11A)含量。[结果] 与假手术组比较,造模后小鼠足部与腹部痛阈均降低(P<0.05)。与EMS模型组比较,温肾消癥汤组小鼠给药后足部痛阈、腹部痛阈均提高(P<0.05)。与EMS模型组比较,温肾消癥汤组小鼠血清,在位内膜,PF,神经系统(丘脑、脊髓、DRG)中COX-2、PGE2,中枢神经系统(丘脑、脊髓)中TRPV1和外周神经系统(DRG)中SCN11A含量均降低(P<0.05)。与阳性对照组比较,温肾消癥汤组小鼠给药后血清、异位病灶、脊髓中PGE2含量均降低(P<0.05)。[结论] 温肾消癥汤能够缓解子宫内膜异位症模型小鼠疼痛,其机制可能与抑制COX-2/PGE2信号通路的过度表达有关。
英文摘要:
      [Objective] To explore the effect of Wenshen Xiaozheng Decoction on pain in mice with endometriosis(EMS) and its mechanism based on cyclooxyfenase-2/prostaglandin E2(COX-2/PGE2) signaling pathway. [Methods] Forty EMS mouse models were established by intraperitoneal injection as modeling group, which was randomly divided into EMS model group(0.2 mL sterile distilled water), Wenshen Xiaozheng Decoction group(0.2 mL Wenshen Xiaozheng Decoction), positive control group(0.2 mL aspirin suspension), and another 10 mice were set as sham operation group. During the 21 days of modeling, the Von Frey fiber test and hot plate test were used to detect mechanical and thermal pain in mice in modeling group and sham operation group. During the 21 days of administration, Von Frey fiber test and hot plate test were used to detect mechanical and thermal pain in EMS model group, Wenshen Xiaozheng Decoction group and positive control group. After 21 days of drug administration, vaginal smears were taken daily to determine the estrous cycle of the mice.During the same estrous cycle, mice were euthanized and serum, peritoneal fluid(PF), endometrial tissue(in situ endometrium, ectopic lesions), thalamus, spinal cord and dorsal root ganglion(DRG) were collected. Enzyme-linked immunosorbent assay(ELISA) was used to determine the contents of COX-2, PGE2, transient receptor potential vanilloid 1(TRPV1), sodium channel protein type 11 subunit alpha (SCN11A). [Results] Compared with sham operation group, after modeling the pain thresholds of the feet and abdomen of the mice decreased(P<0.05). Compared with EMS model group, the mice in Wenshen Xiaozheng Decoction group showed an increase in foot and abdominal pain thresholds after administration(P<0.05). Compared with EMS model group, the mice in Wenshen Xiaozheng Decoction group showed the expression levels of COX-2, PGE2 in serum, in situ endometrium, PF, nervous system (thalamus, spinal cord, DRG),TRPV1 in central nervous system (thalamus, spinal cord), and SCN11A in peripheral nervous system(DRG) decreased(P<0.05). Compared with positive control group, the expression of PGE2 levels in serum, ectopic lesions and spinal cord of the mice in Wenshen Xiaozheng Decoction group decreased after administration(P<0.05). [Conclusion] Wenshen Xiaozheng Decoction can alleviate pain in EMS model mice, and its mechanism may be related to inhibiting the overexpression of COX-2/PGE2 signaling pathway.
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