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乳酸对类风湿关节炎患者外周血CD4+T细胞亚群的调控作用
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作者 黄会娜 赵静 +3 位作者 赵祥格 白自然 李霞 王冠 《北京大学学报(医学版)》 CAS CSCD 北大核心 2024年第3期519-525,共7页
目的:研究类风湿关节炎(rheumatoid arthritis,RA)患者血清乳酸水平及其与疾病活动度的关系,分析乳酸对RA患者外周血中CD4+T细胞的活化、分泌细胞因子能力以及对CD4+T细胞亚群的作用。方法:选择大连医科大学附属第二医院风湿免疫科2019... 目的:研究类风湿关节炎(rheumatoid arthritis,RA)患者血清乳酸水平及其与疾病活动度的关系,分析乳酸对RA患者外周血中CD4+T细胞的活化、分泌细胞因子能力以及对CD4+T细胞亚群的作用。方法:选择大连医科大学附属第二医院风湿免疫科2019年10月至2021年9月连续收治的RA患者作为病例组,同期与RA患者性别年龄相匹配的大连医科大学附属第二医院体检中心健康人(healthy control,HC)作为对照组,收集两组外周血,乳酸检测试剂盒检测上清液中乳酸含量,并分析其与RA患者疾病评分的相关性。用乳酸刺激后,通过流式细胞术检测所有病例组RA患者外周血中CD4+T细胞的活化水平、CD4+T细胞亚群的比例以及CD4+T细胞分泌的细胞因子。结果:RA患者(n=66)的血清乳酸水平[(5.13±1.01)mmol/L vs.(1.72±0.91)mmol/L,P<0.001]明显高于HC(n=60),且与RA患者DAS28(disease activity score in 28 joints)-C反应蛋白(C-reactive protein,CRP)评分有相关性(r=0.273,P=0.029),乳酸浓度>5 mmol/L较浓度≤5 mmol/L的类风湿因子(rheumatoid factor,RF)[197.50(26.03,783.00)IU/mL vs.29.30(0.00,102.60)IU/mL,P<0.01]和CRP[37.40(11.30,72.60)mg/L vs.5.83(2.36,12.45)mg/L,P<0.001]的表达均升高,而红细胞沉降率(erythrocyte sedimentation rate,ESR)[42.00(19.00,77.00)mm/h vs.25.00(12.50,45.50)mm/h,P>0.05]和抗环瓜氨酸多肽(cyclic citrullinated peptied,CCP)抗体[82.35(17.70,137.00)RU/mL vs.68.60(25.95,119.70)RU/mL,P>0.05]的表达差异无统计学意义。与对照组HC相比,乳酸处理组的RA患者CD4+T细胞表面PD-1(46.15%±8.54%vs.41.67%±9.98%,P<0.001)、诱导共刺激分子(inducible costimulatory molecule,ICOS)(25.77%±8.60%vs.18.65%±7.94%,P<0.01)和CD25(25.89%±5.80%vs.22.25%±4.59%,P<0.01)的表达明显升高;乳酸处理组的RA患者CD4+T细胞中Th17(4.62%±1.74%vs.2.93%±1.92%,P<0.05)、外周辅助性T(peripheral helper T,Tph)细胞(28.02%±6.28%vs.20.32%±5.82%,P<0.01)的比例升高;乳酸处理组的RA患者CD4+T细胞中IL-21(5.73%±1.59%vs.4.75%±1.71%,P<0.05)的表达上调。结论:RA患者血清乳酸水平升高,促进了RA患者CD4+T细胞活化和分泌IL-21,以及上调了RA患者Th17、Tph细胞的比例。 展开更多
关键词 类风湿关节炎 乳酸 CD4+T细胞 外周辅助性T细胞
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Involvement of A5/A7 noradrenergic neurons and B2 serotonergic neurons in nociceptive processing:a fiber photometry study
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作者 Shunpei Moriya Akira Yamashita +6 位作者 Daiki Masukawa Junichi Sakaguchi Yoko Ikoma Yoshimune Sameshima Yuki Kambe Akihiro Yamanaka Tomoyuki Kuwaki 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第4期881-886,共6页
In the central nervous system,the A6 noradrenaline(NA)and the B3 serotonin(5-HT)cell groups are well-recognized players in the descending antinociceptive system,while other NA/5-HT cell groups are not well characteriz... In the central nervous system,the A6 noradrenaline(NA)and the B3 serotonin(5-HT)cell groups are well-recognized players in the descending antinociceptive system,while other NA/5-HT cell groups are not well characterized.A5/A7 NA and B25-HT cells project to the spinal horn and form descending pathways.We recorded G-Ca MP6 green fluorescence signal intensities in the A5/A7 NA and the B25-HT cell groups of awake mice in response to acute tail pinch stimuli,acute heat stimuli,and in the context of a non-noxious control test,using fiber photometry with a calcium imaging system.We first introduced G-Ca MP6 in the A5/A7 NA or B25-HT neuronal soma,using transgenic mice carrying the tetracycline-controlled transactivator transgene under the control of either a dopamineβ-hydroxylase or a tryptophan hydroxylase-2 promoters and by the site-specific injection of adeno-associated virus(AAV-Tet O(3 G)-G-Ca MP6).After confirming the specific expression patterns of G-Ca MP6,we recorded G-Ca MP6 green fluorescence signals in these sites in awake mice in response to acute nociceptive stimuli.G-Ca MP6 fluorescence intensity in the A5,A7,and B2 cell groups was rapidly increased in response to acute nociceptive stimuli and soon after,it returned to baseline fluorescence intensity.This was not observed in the non-noxious control test.The results indicate that acute nociceptive stimuli rapidly increase the activities of A5/A7 NA or B25-HT neurons but the non-noxious stimuli do not.The present study suggests that A5/A7 NA or B25-HT neurons play important roles in nociceptive processing in the central nervous system.We suggest that A5/A7/B2 neurons may be new therapeutic targets.All performed procedures were approved by the Institutional Animal Use Committee of Kagoshima University(MD17105)on February 22,2018. 展开更多
关键词 A5 NA neurons A7 NA neurons B25-HT neurons DBH-tTA mice fiber photometry G-CaMP6 mCherry monoaminergic signaling nociception tph-t TA mice
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