读书笔记
当你快速翻阅这本书时，纸张会切入你的一根手指。 人体就像一个管弦乐队一样，伤口愈合是一首由四个重叠乐章组成的交响乐：止血、炎症、增殖和成熟。 止血的英文(Hemostasis)=由血液+停止两部分构成。 这是身体试图止血。 当纸切开皮肤时，血管破裂会使循环中的血小板暴露于胶原蛋白中，胶原蛋白形成位于血管壁内衬下面的有弹性的结缔组织基质。 这种接触启动了血液凝固过程，引发凝血级联反应，这是血小板和化学信使之间的生化对位，导致凝块形成并奠定修复细胞可以发挥作用的基质。 承担起驾驶员的协调职责，血小板释放的细胞因子推动管弦乐队进入下一个乐章，该乐章以炎症反应的渐强开始。
在这快速而夸张的第二乐章中，中性粒细胞是最先设定紧迫旋律的白细胞。 这些吞噬细胞协调先天性和适应性免疫反应。 它们被血小板释放的介质所吸引，从而受到化学伤害。 这些介质还会使该区域的血管更加渗漏，促进更多白细胞的迁移，并顺便使伤口周围的皮肤肿胀。 中性粒细胞会产生更多的炎症细胞因子，例如 IL-1α 和 IL-1β，通过调用其他白细胞通过协调、不协调和最终解决来分层和谐，从而增强炎症反应。 当中性粒细胞开始吞噬细菌时，它们就开始了这种谐波探索。
巨噬细胞和白细胞是下一个加入炎症运动的白细胞，其中巨噬细胞处于领先地位。 它们通过释放称为自由基的分子（例如活性氧）来阻止细菌的生长。 这些自由基会对细菌和我们自己的细胞造成损害。 巨噬细胞还释放一氧化氮，这也会导致局部血管扩张，通过其他免疫细胞为受伤部位带来更多的血液援助。 那是低音下降的时候。 当一氧化氮合成受到损害（如糖尿病）时，伤口愈合也会受到损害。 在发挥作用的同时，巨噬细胞也会清理舞台，吞噬死亡的细菌和其他碎片，并使用酶去除和消化伤口上的死亡组织。 它们还调节新皮肤在其上生长的脚手架的创建。 同时，他们呼吁并邀请将增殖形成新皮肤的细胞和将刺激新血管生长的细胞的参与。
伤口愈合的第三个动作是增殖。 新的声音出现，带来了修复的希望。 成纤维细胞、内皮细胞和上皮细胞在那里设定情绪。 它们受到血小板和巨噬细胞释放的细胞因子和生长因子的诱导，沉积出治愈皮肤所需的物质。 而炎症运动则充满了张力。 成纤维细胞迁移到伤口部位，在那里产生足够的胶原蛋白，这表明伤口修复的精确、显着的生物控制。 构成血管内壁的内皮细胞会产生新血管，这一过程称为血管生成。 同样，形成皮肤外层的上皮细胞在伤口边缘开始增殖，以响应相同的炎症细胞因子和生长因子来覆盖伤口。
最后的乐章，结局，是成熟。 在这里，前一个乐章的主题被分解，并阐述了一个更强但更慢的变奏——慢板。 原来的凝块被溶解，最初沉积的胶原蛋白被另一种胶原蛋白取代，从而增加了伤口的整体拉伸强度。 构成伤口愈合床的肉芽组织被疤痕所取代。 然后，这种运动会持续数月，重塑发生在细胞水平上，细胞与它们产生的细胞外基质和周围的细胞外基质之间进行着美妙的呼唤和反应。 三个月后，疤痕达到最大抗拉强度，仅为未受伤皮肤的 80%。 免疫细胞安静下来，伤口修复过程停止，愈合完成。
As you speed through the pages of this book, the paper slices into one of your fingers. Cue the orchestra, Wound healing is a symphony in four overlapped movements: hemostasis, inflammation, proliferation, and maturation. Hemostasis = blood + stoppage. It is the body’s attempt to staunch bleeding. When paper slices skin, the rupture of blood vessels exposes circulating platelets to the protein collagen, which forms the stretchy matrix of connective tissue that sits right under the vessel wall’s inner lining. This contact starts the process of blood clotting, setting off the coagulation cascade, a biochemical counterpoint between platelets and chemical messengers, that leads to clot formation and laying down the matrix upon which repair cells can work. Assuming the coordinating duties of conductor, cytokines released by platelets motion the orchestra to the next movement, which opens with a crescendo in the inflammatory response.
In this second movement, which is fast and bombastic, neutrophils are the first white blood cells to set the urgent melody. These are phagocytes that harmonize the innate and adaptive immune responses. They are chemically drawn to the injury by the mediators that the platelets released. These mediators also make the blood vessels in the area leakier, facilitating the migration of more white blood cells- and incidentally swelling the skin around the cut. Neutrophils make even more inflammatory cytokines, such as IL-1alpha and IL-1beta, amping up the inflammatory response by calling in other white blood cells to layer the harmony, by way of consonance, dissonance, and ultimately resolution. Neutrophils tart this harmonic exploration as they begin eating up bacteria.
Macrophages and leukocytes are the next white blood cells to join the inflammatory movement, with macrophages taking the lead. They stop bacteria in their tracks by releasing molecules called free radicals, such as reactive oxygen species. These free radicals cause damage to the bacteria and to our own cells. Macrophages also release nitric oxide, which also causes local blood vessels to dilate, bringing more blood-borne assistance by way of other immune cells to the site of injury. That’s when the bass drops. When nitric oxide synthesis is impaired as it is in diabetes, wound healing is also impaired. As they play their part, macrophages also clean up the stage, phagocytizing dead bacteria and other debris and using enzymes to remove and digest dead tissue from the wound. They also regulate the creation of the scaffolding upon which the new skin will grow. At the same time, they call on and invite the participation of cells that will proliferate to make the new skin and cells that will stimulate the growth of new blood vessels.
The third movement of wound healing is proliferation. New voices emerge, bringing the promise of repair. Fibroblasts, endothelial cells, and epithelial cells set the mood there. They are coaxed by the cytokines and growth factors released by platelets and macrophages to lay down the substances needed to heal the skin. While the inflammatory movement was full of tension. Fibroblast migrate to the wound site, where they produce collagen just until enough has been laid down - indicating the precise, remarkable biological control of wound repair. Endothelial cells, which constitute the inner lining of blood vessels, create new blood vessels - a process called angiogenesis. Likewise, epithelial cells, which form the skin’s outer layer, start proliferating at the wound’s edges to cover it up in response to the same inflammatory cytokines and growth factors.
The final movement, the denouement, is maturation. Here the theme of the prior movement is broken down, and a stronger but slower variation is elaborated - adagio. The original clot is dissolved, and the collagen that was initially laid down is replaced with another version that increases the wound’s overall tensile strength. Granulation tissue, which makes up the wound healing bed, is replaced with a scar. Then the movement continues over months, with remodeling occurring on the cellular level, in a beautiful call-and-response between the cells and the extracellular matrix that they create and that surrounds them. After three months, the scar reaches its maximal tensile strength, just 80 percent that of unwounded skin. The immune cells go quiet, the wound repair process switches off, and the healing is complete.
