【原】长期神经病理性疼痛行为学改变与突触可塑性和边缘回路改变的相关性研究：一项小鼠的对照观察研究（十九）

新用户1882ga2h 2022-06-27 发布于山东

展开全文

英语晨读 ·

山东省立医院疼痛科英语晨读已经坚持10余年的时间了，每天交班前15分钟都会精选一篇英文文献进行阅读和翻译。一是可以保持工作后的英语阅读习惯，二是可以学习前沿的疼痛相关知识。我们会将晨读内容与大家分享，助力疼痛学习。

本次文献选自Francesca Guidaa，Monica Iannottaa，Gabriella Misso, et al. Pain. 2022.本次学习由李芸主治医师主讲。

Of note, 11 genes resulted commonly upregulated to a significant extent both in the hippocampus and in PFC of the 12-month sham mice compared with the 1-month ones (Fig. 5C). On the other hand, the proinflammatory cytokines CCL2, CCL5, and IL12A, as well as the costimulator of T-cell activation and proliferation CD86, were upregulated only in the cortex of the 12-month sham mice compared with the 1-month ones (Fig. 5D and E). The PANTHER software analysis displayed the prominent modulation of inflammation mediated by chemokine and cytokine signaling pathways and T-cell activation (Fig. S3B, available at http://links./PAIN/B547).

值得注意的是，与1个月的假手术组相比，12个月的假手术组的海马区和PFC的11个基因普遍上调，且幅度很大（图5C）。另一方面，与1个月的假手术组相比，促炎症细胞因子CCL2、CCL5、IL12A以及T细胞活化和增殖的刺激因子CD86只在12个月的假手术组的大脑皮层中被上调（图5D和E）。PANTHER软件分析显示了由趋化因子和细胞因子信号通路和T细胞激活介导的炎症的突出调节（图S3B）。

Overall, these data demonstrate the existence of an enhanced neuroinflammation status in old brain, as demonstrated by the higher amount of proinflammatory and stress-associated mediators in older mice compared with the younger ones. Moreover, these factors are mainly expressed in the hippocampal region compared with the cortex. The same pattern of genes was analysed to compare sham and SNI mice coupled on the basis of brain area and injury duration (Fig. 6). As a result, we observed the significant upregulation of 26 genes in the hippocampus of the 1-month SNI mice compared with the 1-month sham animals (Fig. 6A and B). Among these genes, there are the apoptosis-related factors Bax and Bcl-2 (3.4 and 4.3-fold), the endothelial marker CD34 (3.4-fold), the pan-macrophage marker CD68 (3.4-fold), the ADP-ribosyl cyclase CD38 (3.6-fold), which acts as a regulator of neuroinflammatory processes in astrocyte-induced neuroprotection, CCR2 (4.3-fold), and macrophage colony-stimulating factor-1 (4.4-fold). A substantial upregulation of the proinflammatory cytokines IL18, IL1B, and IL7 (2.6-fold, 3.5-fold, and 9.6-fold, respectively) was also recorded, together with the inflammatory mediators PTGS2, NFkB1 and 2, STAT6, and IKBKB by 2.7-fold, 5.0-fold, 2.5-fold, 3.3-fold, and 6.9-fold, respectively. The activation of the classical pathway of the complement system was also revealed by 5.3-fold upregulation of C3 gene. A possible rebound effect of these multiple proinflammatory stimuli could be the reason for the huge increase of SOCS2 expression (11.1-fold). The immunosuppressive cytokine TGF-b1, which acts as a pivotal controller of cell growth and differentiation and of tissue repair after injury, was upregulated by 3.2-fold, but a simultaneous induction of its negative regulator SMAD7 (3.7-fold) was observed too. The expression of angiogenic factors EDN1 and VEGFA, as well as the adhesion molecule VCAM1, was also found strongly induced (3.6-, 6.5-, and 3.4-fold, respectively). Worthy of note is the huge induction of transferrin receptor (TFRC, 5-fold). The PANTHER software revealed the representation of the most affected pathways in the hippocampus of the 1-month SNI mice compared with the 1-month sham animals (Fig. S3C, available at http://links./PAIN/B547), showing 8 genes involved in inflammation mediated by chemokine and cytokine signaling pathways, 5 genes in apoptotic pathway, 4 in CCKR map, other 4 in Toll receptor signaling pathway, and other genes variously involved in B-cell activation, T-cell activation, TGF-b, Wnt, PDGF, and endothelin signaling pathways.

总的来说，这些数据证明了老龄大脑中存在更强的神经炎症状态，这表现在12飞月组与1个月组相比有更多的促炎和应激相关的介质。此外，这些介质因素主要在海马区表达。我们观察到1个月的SNI小鼠与1个月的假手术组相比，在海马区有26个基因明显上调（图6A和B）。在这些基因中，主要有凋亡相关因子Bax和Bcl-2（3.4和4.3倍），内皮细胞标志物CD34（3.4倍），泛巨噬细胞标志物CD68（3.4倍），CD38（3. 6倍）， CCR2（4.3倍），和巨噬细胞集落刺激因子-1（4.4倍）。促炎症细胞因子IL18、IL1B和IL7分别上调了2.6倍、3.5倍和9.6倍，炎症介质PTGS2、NFkB1和2、STAT6和IKBKB分别上调了2.7倍、5.0倍、2.5倍、3.3倍和6.9倍。补体系统的经典途径也被激活，C3被上调5.3倍。细胞因子信号转导抑制因子 2 SOCS2的表达量大幅增加（11.1倍）。免疫抑制细胞因子TGF-b1作为细胞生长和分化以及损伤后组织修复的关键因子，被上调了3.2倍，但同时也观察到其负调控因子SMAD7的上调（3.7倍）。血管生成因子EDN1和VEGFA以及粘附分子VCAM1的表达也被显著诱导（分别为3.6、6.5和3.4倍）。值得注意的是转铁蛋白受体（TFRC，5倍）的诱导表达。PANTHER软件显示，与1个月的假手术组相比，1个月的SNI小鼠海马区中显示有8个基因参与由趋化因子和细胞因子信号通路介导的炎症，5个基因参与凋亡通路，4个参与CCKR图谱，其他4个参与Toll受体信号通路，还有其他不同的基因参与B细胞激活、T细胞激活、TGF-b、Wnt、PDGF以及内皮素信号通路。