Notch3信号介导小胶质细胞活化在慢性前列腺炎疼痛中的作用

目的观察Notch3介导L5~S2脊段背角小胶质细胞活化在慢性前列腺炎疼痛中的作用。方法大鼠分为实验组(慢性前列腺炎组)和对照组,实验组通过完全弗氏佐剂(CFA)注射前列腺来制作大鼠慢性前列腺炎疼痛模型,对照组注射生理盐水,采用热辐射甩尾痛阈测定和前列腺组织病理学检查鉴定疼痛模型,分别在注射CFA后0、4、12、24 d,采用qRT-PCR检测L5~S2脊段后角小胶质细胞活化标志物IBA-1和受体Notch3 mRNA的表达,采用ELISA检测小胶质细胞炎症因子TNF-α和IL-1β的分泌,并在鞘内注射小胶质细胞和Notch3抑制剂后检测小胶质细胞TNF-α和IL-1β蛋白的表达。结果前列腺组织病理和热痛域实验证实慢性前列腺炎疼痛模型建立成功。实验组大鼠Notch3、IBA-1、TNF-α及IL-1β的表达在第4天开始增加,第12天达到最高水平,第24天开始下降,均显著高于对照组,差异有极显著性统计学意义(P<0.01)。抑制小胶质细胞和Notch3受体后,TNF-α和IL-1β的分泌明显减少(P<0.05)。结论慢性前列腺炎疼痛中Notch3介导L5~S2脊段中枢小胶质细胞活化,炎症因子分泌增加,与慢性前列腺炎呈现的持续顽固神经炎性疼痛有关。

Effect of Notch3 signal mediated microglia activation on the neuroregulation of chronic prostatitis pain

Objective To observe the role of Notch3 mediated activation of microglia in the dorsal horn of L5-S2 spinal cord in chronic prostatitis pain.Methods The rats were divided into the experimental group(the chronic prostatitis group)and the control group.The experimental group was injected with complete Freund′s adjuvant(CFA)to make chronic prostatitis pain model.The control group was injected with normal saline,and the pain model was identified by heat radiation tail flick pain threshold measurement and prostate histopathology examination.The expression of the activation marker ionized calcium binding adaptor molecule 1(IBA-1)and the receptor Notch3 of microglia in the posterior horn were detected by qRT-PCR at 0,4,12,24 days after the CFA injection.The secretion of the inflammatory cytokines TNF-αand IL-1βin microglia were detected by ELISA.Furthermore,the expression of TNF-αand IL-1βof microglia were detected after intrathecal injection of microglia and Notch3 inhibitor.Results The chronic prostatitis pain model was confirmed by pathological examination and hot pain field experiment.The expressions of Notch3,IBA-1,TNF-α,IL-1βin the experimental group began to increase on the 4th day,and they reached the maximum level on the 12th day,and they began to decrease on the 24th day,which were all significantly higher than those in the control group(P<0.01).The secretion of TNF-αand IL-1βdecreased significantly after inhibition of microglia and Notch3 receptor(P<0.05).Conclusion In chronic prostatitis pain,Notch3 mediates the activation of microglia in L5-S2 spinal cord center,and it results in the increase of inflammatory factor secretion,which is related to the persistent and refractory neuritis pain in chronic prostatitis.