构建“细胞桥”用于脊髓损伤后修复

在小鼠实验中，科学家向脊髓损伤部位引入了一种特定类型的重组蛋白，这些被称为周细胞的细胞已在损伤区大量聚集。结果显示，一旦暴露于这种蛋白，周细胞就会改变形状，抑制某些分子的产生并分泌其他分子，从而形成支持轴突再生的“细胞桥”——轴突是神经细胞体传递信息的细长突起。

研究人员观察到，接受单次生长因子蛋白注射治疗的受伤小鼠出现了轴突再生，并且这些动物的后肢也恢复了运动能力。一项涉及人类细胞的实验表明，该结果并不局限于小鼠。

资深研究作者、俄亥俄州立大学医学院神经科学副教授安德里亚·泰代斯基表示：“还有很多东西可以学习，也有很多方面可以拓展，但随着研究的深入，我们对这种单次治疗的效力及其有效性感到愈发惊讶。这一发现不仅限于脊髓损伤——它对脑损伤、中风以及神经退行性疾病也具有重要意义。”

研究人员表示，这项工作强调了血管重建对于脊髓损伤后神经功能恢复的重要性。

第一研究作者、俄亥俄州立大学神经科学助理教授孙文静表示：“脊髓损伤之所以严重，不仅是因为它们阻碍了信息跨越损伤部位的传递，还因为所有的血管结构和功能也都受到了损害。即使你能够重建从头到尾的神经连接，除非你处理好其他所有崩溃的问题，否则整体效果仍无法达到最佳。”

该研究于4月18日发表在《分子治疗》杂志上。

先前的研究表明周细胞会干扰脊髓损伤的恢复，这导致一些科学家建议将其从损伤部位清除以辅助修复。但癌症研究表明，当周细胞暴露于一种称为血小板衍生生长因子BB（PDGF-BB）的蛋白时，其特性会发生变化——这是肿瘤生成自身血液供应的一种方式。在癌症治疗中，目标是阻断PDGF-BB信号传导。

早期的神经科学研究也表明，周细胞具有高度的“可塑性”，这意味着它们对微环境的变化——包括PDGF-BB的存在——非常敏感。泰代斯基及其同事看到了利用这种细胞-蛋白关系来稳定脊髓损伤周围血管的潜力。在此过程中，他们发现新生的血管建立了一条供再生轴突跟随的路径。

* *Draft:* 从影像学研究开始，研究团队表明，当脊髓被切断时，周细胞会随时间迁移到损伤部位，但不会促进支持轴突再生所需的功能性血管的生长。 * *Refinement:* "Starting with..." implies the order of presentation or the first phase of the study. "Severed" usually implies a complete cut, so "横断" is precise in a spinal cord context. "Over time" -> 随着时间的推移. * *Paragraph 2:* * "In cell-culture experiments, the researchers established a "carpet" of pericytes, added PDGF-BB, and then placed a layer of adult mouse sensory neurons on top and evaluated how much axons grew in 24 hours." * *Key terms:* cell-culture experiments (细胞培养实验), "carpet" (“地毯”/铺展层), PDGF-BB (血小板衍生生长因子-BB), adult mouse sensory neurons (成年小鼠感觉神经元), axons (轴突). * *Draft:* 在细胞培养实验中，研究人员建立了一层周细胞“地毯”，加入PDGF-BB，然后在上面放置一层成年小鼠感觉神经元，并评估24小时内轴突生长了多少。 * *Refinement:* "Established a 'carpet'" -> 铺设了一层周细胞“地毯”. "Evaluated how much axons grew" -> 评估轴突的生长量/生长程度. * *Paragraph 2 (continued):* * "The treated axons grew nearly as much as healthy axons extend under normal conditions." * *Draft:* 经过处理的轴突生长量几乎与健康轴突在正常条件下的延伸量相当。 * *Refinement:* "Extend" here acts as the verb for the growth action. "Growth" vs "extension". "生长量" works well. * *Paragraph 3:* * "PDGF-BB alone did not produce this result." * *Draft:* 单独使用PDGF-BB并没有产生这种结果。 * *Paragraph 3 (continued):* * "Instead, experiments showed that pericytes combined with the growth factor rearranged fibronectin, a multifunctional adhesive glycoprotein that plays a critical role in tissue repair, cell attachment and motility." * *Key terms:* growth factor (生长因子), rearranged (重排), fibronectin (纤连蛋白), multifunctional adhesive glycoprotein (多功能粘附糖蛋白), tissue repair (组织修复), cell attachment (细胞附着), motility (运动能力/迁移力). * *Draft:* 相反，实验表明，周细胞与该生长因子结合后重排了纤连蛋白，这是一种在组织修复、细胞附着和运动中起关键作用的多功能粘附糖蛋白。 * *Paragraph 3 (continued):* * "The cells themselves also change shape, becoming more elongated." * *Draft:* 细胞本身也改变了形状，变得更加细长。 * *Paragraph 4:* * "'We know these cells are going to infiltrate and deposit at the lesion epicenter. These elongated fiber structures that they become are far more permissive in promoting axons to regenerate from one end to the other and bypass the injury,' Tedeschi said." * *Key terms:* infiltrate (浸润/渗透), deposit (沉积), lesion epicenter (损伤中心/病灶中心), elongated fiber structures (细长的纤维结构), permissive (允许的/有利的/许可性的), bypass (绕过). * *Draft:* Tedeschi说：“我们知道这些细胞会浸润并沉积在损伤中心。它们变成的这些细长纤维结构在促进轴突从一端再生到另一端并绕过损伤方面具有更高的许可性。” * *Refinement:* "Permissive" in biology often refers to a permissive environment. "Far more permissive" -> 更加有利/更具许可性. "Permissive" is a specific term, but "有利" (favorable) or "允许性更强" is often used. Let's stick to "允许性" or "有利". "Permissive in promoting" -> 更有利于促进. Let's use "更具许可性" or "更有利". "Permissive substrate" is a common concept. Let's translate as "更有利于". Or strictly "更具许可性". Let's go with "更具许可性" to be scientifically precise, or "更加有利" for readability. Given the instruction to be professional, "更具许可性" or "更有利" are both good. Let's use "更有利于" for flow or "更具许可性" for precision. Let's try: "它们转变形成的这些细长纤维结构在促进轴突从一端再生至另一端并绕过损伤方面，具有更强的许可性。" * *Paragraph 5:* * "'To extend the clinical relevance of our findings, we cultured mouse neurons on top of human pericytes that were exposed to PDGF-BB, and that was sufficient to trigger a growth-promoting effect, suggesting that this might really be a generalized phenomenon that is not restricted to mice.'" * *Key terms:* clinical relevance (临床相关性), cultured (培养), exposed to (暴露于/经...处理), trigger (触发), growth-promoting effect (促生长效应), generalized phenomenon (普遍现象), restricted to (局限于). * *Draft:* “为了扩展我们发现的临床相关性，我们在经PDGF-BB处理的人类周细胞上培养小鼠神经元，这足以触发促生长效应，表明这可能确实是一种不局限于小鼠的普遍现象。” * *Paragraph 6:* * "Turning to experiments in animals with spinal cord injury, researchers waited for seven days after the injury -- the equivalent of about nine months in a human adult -- before injecting a single dose of PDGF-BB at the injury site." * *Key terms:* animals with spinal cord injury (脊髓损伤动物), equivalent (相当于), single dose (单剂量). * *Draft:* 转向脊髓损伤动物实验，研究人员在损伤后等待了七天——相当于人类成年人大约九个月的时间——才在损伤部位注射单剂量的PDGF-BB。 * *Paragraph 6 (continued):* * "Analysis of tissue four weeks after the injury showed that the PDGF-BB injection produced robust axon regenerative growth compared to the axon response in injured control mice." * *Key terms:* Analysis of tissue (组织分析), robust (强劲的/显著的), injured control mice (受伤对照组小鼠). * *Draft:* 损伤后四周的组织分析显示，与受伤对照组小鼠的轴突反应相比，注射PDGF-BB产生了强劲的轴突再生生长。 * *Paragraph 7:* * "'When we looked at formation of these pericyte structures that crossed the injury site, we saw the treatment promoted the growth of these bridges. And most if not all of these regenerating axons were able to escape the injury site by riding these cellular bridges that have formed in response to PDGF-BB administration,' Sun said." * *Key terms:* pericyte structures (周细胞结构), bridges (桥接), escape (逃离/逃逸), riding (搭乘/利用), cellular bridges (细胞桥), administration (给药). * *Draft:* Sun说：“当我们观察穿过损伤部位的这些周细胞结构的形成时，我们看到治疗促进了这些桥接的生长。而且，如果不是全部，也是大多数再生轴突能够通过搭乘这些响应PDGF-BB给药而形成的细胞桥，逃离损伤部位。” * *Refinement:* "Ride" is metaphorical. "利用" (utilize) or "沿着" (along) is more formal, but "搭乘" keeps the imagery. "Escape" -> 逃离/离开. "Escape the injury site" usually means growing out of the inhibitory environment. "离开损伤部位" is neutral. "逃离" fits the context of being trapped. Let's use "通过...逃离损伤部位". * *Paragraph 8:* * "Electrophysiological and movement assessments of injured animals treated with PDGF-BB detected sensory activity beyond the lesion site and showed the mice regained better control of their hind limbs compared to control mice." * *Key terms:* Electrophysiological (电生理学), movement assessments (运动评估), sensory activity (感觉活动 * *Draft:* 对修复过程中炎症蛋白存在的分析表明，给予 PDGF-BB 不仅促进轴突再生，还能减轻炎症。 * *Refinement:* "Analysis of the presence..." can be smoothed to "对修复过程中炎症蛋白的分析..." or "分析修复过程中炎症蛋白的存在...". "Administration" is often translated as "给予" or "施用" in medical contexts. "Promotes" -> 促进. "Reduces" -> 减轻. * *Final Polish:* 对修复过程中炎症蛋白的分析表明，给予 PDGF-BB 不仅促进了轴突再生，还减轻了炎症。 * *Sentence 2:* "RNA sequencing showed that spinal cord injury led to decreased gene expression by pericytes, but that the cells retained their core properties and did not convert into a different kind of cell -- for example, a cell type that could end up being destructive to the injury environment." * *Key terms:* RNA sequencing (RNA测序), spinal cord injury (脊髓损伤), gene expression (基因表达), pericytes (周细胞), core properties (核心特性), convert into (转化为), destructive (破坏性的), injury environment (损伤环境). * *Draft:* RNA测序显示，脊髓损伤导致周细胞的基因表达降低，但这些细胞保留了其核心特性，并没有转化为不同类型的细胞——例如，一种最终可能对损伤环境具有破坏性的细胞类型。 * *Refinement:* "Decreased gene expression by pericytes" -> 周细胞的基因表达降低. "End up being" -> 最终变得/最终成为. * *Final Polish:* RNA 测序显示，脊髓损伤导致周细胞的基因表达降低，但这些细胞保留了其核心特性，并未转化为不同类型的细胞——例如，那种最终可能对损伤环境造成破坏的细胞类型。 * *Sentence 3:* "There was a decrease in some classical pericyte markers, but a gain of some additional function linked to the attempt to rebuild cellular bridges and functional vessels," Sun said. * *Key terms:* classical pericyte markers (经典周细胞标志物), gain of some additional function (获得了一些额外功能), rebuild cellular bridges (重建细胞桥), functional vessels (功能性血管). * *Draft:* “一些经典的周细胞标志物有所减少，但获得了一些与重建细胞桥和功能性血管的尝试相关的额外功能，”Sun说。 * *Refinement:* "Linked to the attempt to..." -> 与...的尝试相关. "Functional vessels" -> 功能性血管. * *Final Polish:* “一些经典的周细胞标志物有所减少，但获得了一些与重建细胞桥和功能性血管尝试相关的额外功能，”Sun 说。 * *Sentence 4:* "From the overall gene signature in our data, they're still classified as a pericyte." * *Key terms:* overall gene signature (整体基因特征/图谱), classified as (归类为). * *Draft:* “根据我们数据中的整体基因特征，它们仍然被归类为周细胞。” * *Refinement:* "Gene signature" is often translated as 基因特征 or 基因图谱. "Classified as" -> 归类为. * *Final Polish:* “根据我们数据中的整体基因特征，它们仍被归类为周细胞。” * *Sentence 5:* "Because Tedeschi, Sun and colleagues have previously shown in mice that gabapentin promotes regeneration of neural circuits after spinal cord injury, there's potential to consider a multipronged approach to therapy, Sun said." * *Key terms:* gabapentin (加巴喷丁), regeneration of neural circuits (神经回路再生), multipronged approach (多管齐下的方法/多途径方法). * *Draft:* Sun说，因为Tedeschi、Sun和同事之前在小鼠身上已经证明加巴喷丁促进脊髓损伤后的神经回路再生，所以有潜力考虑一种多管齐下的治疗方法。 * *Refinement:* "Multipronged approach" -> 多管齐下的方法. * *Final Polish:* Sun 表示，由于 Tedeschi、Sun 及其同事此前已在小鼠身上证实加巴喷丁能促进脊髓损伤后的神经回路再生，因此有必要考虑采用一种多管齐下的治疗方法。 * *Sentence 6:* "We could combine both -- modulating intrinsic properties of adult neurons with a drug, and what we are doing here, modulating the non-neuronal environment to produce cellular interactions that provide a more permissive substrate for the neuron to grow on," she said. * *Key terms:* modulating (调节), intrinsic properties (内在特性), adult neurons (成年神经元), non-neuronal environment (非神经元环境), cellular interactions (细胞相互作用), permissive substrate (允许性基质/容许性底物). * *Draft:* “我们可以结合两者——用药物调节成年神经元的内在特性，以及我们在这里做的，调节非神经元环境以产生细胞相互作用，为神经元生长提供更具允许性的基质，”她说。 * *Refinement:* "Permissive substrate" is a specific biological term. "允许性基质" or "容许性底物". "Substrate" in the context of cells growing on something is usually 基质 or 底物. I will use "基质" as it fits the tissue engineering/cell biology context well here. * *Final Polish:* “我们可以将两者结合起来——利用药物调节成年神经元的内在特性，以及我们在本研究中所做的工作，调节非神经元环境以产生细胞相互作用，从而为神经元的生长提供更具允许性的基质，”她说。 * *Sentence 7:* "More work is planned to determine the precise timing for administration of PDGF-BB -- with the presumption that pericytes take some time to migrate to the injury -- as well as the ideal concentration of the treatment and a potential time-released delivery system." * *Key terms:* precise timing (精确时机), presumption (假设/推测), migrate (迁移), ideal concentration (理想浓度), time-released delivery system (缓释递送系统/定时释放递送系统). * *Draft:* 计划进行更多工作来确定给予PDGF-BB的精确时机——假设周细胞需要一些时间迁移到损伤部位——以及治疗的理想浓度和潜在的缓释递送系统。 * *Refinement:* "Time-released" usually means sustained release or controlled release. "缓释" is the standard term. "Delivery system" -> 递送系统. * *Final Polish:* 研究人员计划开展更多工作，以确定给予 PDGF-BB 的精确时机——基于周细胞迁移至损伤部位需要一定时间的假设——以及治疗的理想浓度和潜在的缓释递送系统。 * *Sentence 8:* "This research was supported by the National Institute of Neurological Disorders and Stroke and Ohio State's Chronic Brain Injury Program." * *Key terms:* National Institute of Neurological Disorders and Stroke (美国国立神经疾病和中风研究所), Ohio State's Chronic Brain Injury Program (俄亥俄州立大学慢性脑损伤项目). * *Draft:* 这项研究得到了美国国立神经疾病和中风研究所以及俄亥俄州立大学慢性脑损伤项目的支持。 * *Refinement:* Standard translation for NINDS is 美国国立神经疾病和中风研究所. * *Final Polish:* 本研究得到了美国国立神经疾病和中风研究所以及俄亥俄州立大学慢性脑损伤项目的支持。 * *Sentence 9:* "Additional co-authors were Elliot Dion, Fabio Laredo, Allyson Okonak, Jesse Sepeda, Esraa Haykal, Min Zhou, Heithem El-Hodiri, Andy Fischer, Juan Peng and Andrew Sas, all of Ohio State, and Jerry Silver of Case Western Reserve University." * *Key terms:* co-authors (共同作者), Ohio State (俄亥俄州立大学), Case Western Reserve University (凯斯西储大学). * *Draft:* 其他共同作者包括俄亥俄州立大学的Elliot Dion, Fabio Laredo, Allyson Okonak, Jesse Sepeda, Esraa Haykal, Min Zhou, Heithem El-Hodiri, Andy Fischer, Juan Peng和Andrew Sas，以及凯斯西储大学的Jerry Silver。 * *Refinement:* Names are usually kept in English in scientific translations unless there are widely known standard Chinese names (which these don't seem to be, except maybe Min Zhou -> 周敏, but usually kept as Min Zhou in author lists to avoid ambiguity). I will keep names in English. * *Final Polish:* 其他