摘要
目的:探讨10-11易位蛋白2(ten-eleven translocation 2,TET2)在小鼠外周组织炎症和炎性疼痛中的作用。方法:采用免疫荧光方法检测野生型(wild-type,WT)小鼠和Tet2^(-/-)小鼠足底皮肤中神经纤维标记物TUJ1的表达与分布;行为学方法检测福尔马林和完全弗氏佐剂(complete Freund's adjuvant,CFA)诱导的疼痛行为;HE染色检测WT小鼠与Tet2^(-/-)小鼠在CFA 7天足底皮肤组织结构;蛋白芯片检测CFA 7天,WT小鼠与Tet2^(-/-)小鼠足底皮肤中差异表达的炎症介质。结果:与WT小鼠相比,Tet2^(-/-)小鼠足底神经纤维分布未见异常;足底注射0.5%福尔马林诱导小鼠出现双时相自发性疼痛,Tet2^(-/-)小鼠比WT小鼠更强烈;足底注射50%CFA诱发WT小鼠和Tet2^(-/-)小鼠出现较长时间的热痛觉过敏和机械性触诱发痛,Tet2^(-/-)小鼠比WT小鼠更严重。在Tet2^(-/-)小鼠,0.5%福尔马林和50%CFA引起的足底肿胀程度比WT明显;CFA注射后7天,Tet2^(-/-)小鼠的足底皮肤真皮层与皮下组织厚度大于WT小鼠。蛋白芯片检测显示,在炎性疼痛条件下,敲除Tet2基因可使104种炎症介质表达发生变化,其中基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)、抗素(resistin)、MMP3等19种炎症介质表达明显上调。结论:Tet2基因参与疼痛的调节。敲除Tet2基因通过释放更多的炎症因子增强炎症反应,从而促进小鼠的急、慢性炎性疼痛行为,表明TET2在外周炎性疼痛中可能发挥抗炎镇痛作用。
Objective:To investigate the role of ten-eleven translocation 2(TET2)protein in peripheral tissue inflammation and acute/chronic inflammatory pain in mice.Methods:Immunofluorescence staining was used to examine the expression and distribution of nerve fiber marker TUJ1 in plantar skin of wild-type(WT)and Tet2^(-/-)mice;Behavioral tests were used to detect Formalin-and complete Freund's adjuvant(CFA)-induced pain;HE staining was used to detect the structure of plantar skin of WT and Tet2^(-/-)mice at CFA 7 d;Protein array was used to detect the differentially expressed inflammatory mediators in the paw of WT and Tet2^(-/-)mice at CFA 7 d.Results:Compared with WT mice,Tet2^(-/-)mice showed similar distribution of plantar nerve fibers.Plantar injection of 0.5%Formalin induced dual-phase spontaneous pain,which was more intense in Tet2^(-/-)mice than that in WT mice.50%CFA induced prolonged heat hyperalgesia and mechanical allodynia in WT and Tet2^(-/-)mice,and pain sensitivity in Tet2^(-/-)mice was more severe than that in WT mice.In Tet2^(-/-)mice,0.5%formalin and 50%CFA induced stronger plantar swelling than that in WT mice.The thickness of the dermis and hypodemis of the Tet2^(-/-)mice was greater than that of WT mice at CFA 7 d.Protein array showed that under the condition of inflammatory pain,knockout of Tet2 gene changed the expression of 104 inflammatory mediators,and 19 of them such as matrix metalloproteinase 9(MMP9),resistin,and MMP3 were significantly up-regulated.Conclusion:Tet2 gene is involved in the regulation of pain.Knockout Tet2 gene induces inflammatory responses by releasing more inflammatory factors to enhance acute and chronic inflammatory pain,indicating that TET2 may play an anti-inflammatory and analgesic role in peripheral inflammatory pain.
作者
孟庆余
李春华
马灵杰
高永静
MENG Qingyu;LI Chunhua;MA Lingjie;GAO Yongjing(Institute of Pain Medicine and Special Environmental Medicine,Nantong University,Nantong 226019,China)
出处
《中国疼痛医学杂志》
CAS
CSCD
北大核心
2022年第10期739-746,共8页
Chinese Journal of Pain Medicine
基金
国家自然科学基金(32030048,31871064)
江苏省自然科学基金(BK20171255)
南通市科技局2020基础科学研究计划(JC2020038)。
