第二十一篇：Oxidative Stress in Atherosclerosis[1]
动脉粥样硬化中的氧化应激
Postulated mechanisms by which cardiovascular risk factors affect ROS generation and endothelial function along the interplay ofoxidant and antioxidant systems, in generation of ROS.
假设的机制：心血管危险因素通过氧化与抗氧化系统的相互作用影响活性氧（ROS）的生成及内皮功能。
Role ofOx-LDL and LOX-1 in atherogenesis and thrombosis.
Ox-LDL和LOX-1在动脉粥样硬化形成和血栓形成中的作用
第二十二篇：Oxidative Stress and Hypertension[2]
氧化应激与高血压
The major source of ROS in the cardiovascular system is the NOX (NADPH oxidase) family. NOX1–4 are p22phox-dependent oxidases, whereas NOX5, a Ca2+-sensitive NOX, does not require p22phox for its activation. In the cardiovascular system, NOXes are regulated by prohypertensive and inflammatory factors, including Ang II (angiotensin II), ET-1 (endothelin-1), aldosterone, salt, growth factors (VEGF [vascular endothelium growth factor] and epidermal growth factor [EGF]), and TNF (tumor necrosis factor). ROS are also generated by eNOS (endothelial nitric oxide synthase) uncoupling, and mitochondrial and endoplasmic reticulum (ER) mechanisms, which are influenced by NOX/ROS. AT1R indicates Ang II type 1 receptor; BH4, tetrahydrobiopterin; ETAR, ET-1 type A receptor; GFR, growth factor receptor; and MR, mineralocorticoid receptor.
心血管系统中活性氧（ROS）的来源：
心血管系统中ROS的主要来源是NOX（NADPH氧化酶）家族。NOX1至NOX4为依赖p22phox的氧化酶，而NOX5是一种钙敏感型NOX，其活化不依赖p22phox。在心血管系统中，NOX酶的活性受多种促高血压和炎症因子的调控，包括血管紧张素II（Ang II）、内皮素-1（ET-1）、醛固酮、盐、各种生长因子（如血管内皮生长因子VEGF和表皮生长因子EGF）以及肿瘤坏死因子（TNF）。此外，ROS还可通过内皮型一氧化氮合酶（eNOS）解偶联、线粒体以及内质网（ER）机制产生，而这些机制亦受NOX/ROS调控影响。
Increased NADPH oxidase (Nox)-induced reactive oxygen species (ROS) generation promotes activation of ER stress signaling pathways and the unfolded protein response that influences vascular function in hypertension.
氧化应激与内质网（ER）应激在高血压中的相互作用：
NADPH氧化酶（Nox）诱导的活性氧（ROS）生成增加，促进内质网应激信号通路及未折叠蛋白反应（UPR）的激活，从而影响高血压中的血管功能。
Main reactions leading to reversible and irreversible oxidation of proteins in cardiovascular cells.
蛋白质的翻译后氧化修饰。 心血管细胞中导致蛋白质可逆性和不可逆性氧化的主要反应过程。
ROS (reactive oxygen species) influence many signaling molecules that regulate cardiovascular function, including kinases, phosphatases, Ca2+ channels, transcription factors, genes. These processes involve Ox-PTM (oxidative posttranslational modifications) of downstream redox-sensitive targets. Oxidative stress causes abnormal redox signaling leading to cardiovascular dysfunction and remodeling in hypertension. Decreased antioxidants contribute to oxidative stress. MMP indicates matrix metalloproteinases; PTP, protein tyrosine phosphatases; and UPR, unfolded protein response.
高血压中参与的氧化还原敏感性信号通路示意图：
活性氧（ROS）影响多种调控心血管功能的信号分子，包括激酶、磷酸酶、钙通道（Ca²⁺通道）、转录因子及相关基因。这些过程涉及下游氧化还原敏感靶点的氧化性翻译后修饰（Ox-PTM）。氧化应激导致异常的氧化还原信号传导，从而引发高血压中的心血管功能障碍和结构重塑。抗氧化物水平的下降亦促进氧化应激的发展。
Prohypertensive factors induce activation of NLRP3 (nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome through ROS (reactive oxygen species). ROS influences signal 1 (cytokines, PAMPS (pathogen-associated molecular patterns, DAMPS (danger-associated molecular patterns), leading to activation of NF-κB (nuclear factor-κB) and gene expression of components of the inflammasome. ROS also influence signal 2, by PAMPS, DAMPS, oxLDL (oxidized low-density lipoprotein), oxPL (oxidized phospholipids), ATP, Ang II (angiotensin II), ET-1 (endothelin-1), aldo (aldosterone), and cations (K+, Ca2+, and Na+). These processes lead to assembly of the inflammasome complex (NLRP3, ASC [apoptosis-associated speck-like protein], and procaspase-1) and consequent activation of caspase-1, cleavage of pro-IL (interleukin)-1β and pro-IL-18, and production of active forms of IL-1β and IL-18, which increase the inflammatory response, fibrosis, and vascular remodeling in hypertension. MR indicates mineralocorticoid receptor; and question mark (?), possible effect.
氧化应激与炎症小体在高血压中的作用：
促高血压因子通过活性氧（ROS）介导NLRP3炎症小体（即含吡啶结构域的NOD样受体家族成员3，nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3）的激活。ROS影响信号1，即细胞因子、PAMPs（病原体相关分子模式）和DAMPs（损伤相关分子模式），从而激活NF-κB（核因子-κB）并诱导炎症小体相关组分的基因表达。
ROS还通过PAMPs、DAMPs、氧化低密度脂蛋白（oxLDL）、氧化磷脂（oxPL）、ATP、血管紧张素II（Ang II）、内皮素-1（ET-1）、醛固酮（aldo）以及钾、钙、钠等阳离子（K⁺、Ca²⁺、Na⁺）影响信号2。这些过程促使炎症小体复合物的组装（包括NLRP3、ASC［凋亡相关斑点样蛋白］和前体caspase-1），进而激活caspase-1，切割前体IL-1β和前体IL-18，生成活性的IL-1β和IL-18，增强炎症反应、纤维化及高血压中的血管重塑。文中缩略词解释如下：MR为盐皮质激素受体；问号（?）表示可能的作用。
Functional effects of oxidative stress in regulatory systems and organs in the pathophysiology of hypertension.
系统生物学、氧化应激与高血压 氧化应激在高血压病理生理过程中对调控系统和器官的功能性影响。
第二十二篇：Oxidative stress and regulated cell death in Parkinson’s disease[3]
帕金森病中的氧化应激和调节性细胞死亡
Due to its lipophilic nature, MPTP can cross the blood-brain barrier after systemic administration. When in the brain, MPTP is metabolized to MPDP+ by MAOB, mainly in astrocytes. Then, MPDP+ diffuses to the intracellular space and is converted by auto-oxidation to the active metabolite MPP+, which concentrates in dopaminergic neurons due to its high affinity for the plasma membrane DATs. Within the neuron, MPP+ can concentrate inside mitochondria, where it inhibits complex I of the electron transport chain, therefore disrupting the electron flux, which leads to decreased ATP synthesis and increased ROS production, especially superoxide.
MPTP在体内代谢的示意图。
由于其亲脂性，MPTP在系统给药后能够穿过血脑屏障。进入脑组织后，MPTP主要在星形胶质细胞中被单胺氧化酶B（MAOB）代谢为MPDP⁺（1-甲基-4-苯基-2,3-二氢吡啶鎓）。随后，MPDP⁺扩散至细胞内空间，并通过自发氧化反应转化为活性代谢产物MPP⁺（1-甲基-4-苯基吡啶鎓）。由于MPP⁺对多巴胺转运体（DATs）具有高度亲和力，因此其在多巴胺能神经元中高度聚集。在神经元内，MPP⁺进一步富集于线粒体中，在此抑制电子传递链的复合物I，导致电子流受阻，进而引发ATP合成减少和活性氧（ROS）生成增加，尤其是超氧阴离子（superoxide）。
详见：
详见：《TNF驱动的程序性坏死机制》
详见：《铁死亡的分子机制》
参考文献：
[1] A. J. Kattoor, N. V. K. Pothineni, D. Palagiri, and J. L. Mehta, “Oxidative Stress in Atherosclerosis,” Nov. 01, 2017, Current Medicine Group LLC 1. doi: 10.1007/s11883-017-0678-6.
[2] K. K. Griendling, L. L. Camargo, F. J. Rios, R. Alves-Lopes, A. C. Montezano, and R. M. Touyz, “Oxidative Stress and Hypertension,” Apr. 02, 2021, Lippincott Williams and Wilkins. doi: 10.1161/CIRCRESAHA.121.318063.
[3] P. A. Dionísio, J. D. Amaral, and C. M. P. Rodrigues, “Oxidative stress and regulated cell death in Parkinson ’ s disease,” Ageing Res Rev, vol. 67, no. January, p. 101263, 2021, doi: 10.1016/j.arr.2021.101263.