硫化氢:生物和病理化学

I. Fomenko, T. Bondarchuk
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摘要

硫化氢(H2S)属于 "气体递质 "家族,可以由酶系统合成,也可以非酶生成。在生理浓度下,它能调节各种器官和组织的一系列生物功能。H2 S 参与生化变化,在癌症、COVID-19、糖尿病和神经退行性病变等疾病的发病机制中发挥重要作用。在致癌过程中,H2S 影响癌细胞增殖,抑制癌细胞凋亡,调节细胞周期、细胞内信号通路,刺激血管生成和癌细胞自噬。在 COVID-19 引起的肺部炎症中,H2S 可破坏粘液中的二硫键,降低粘度;阻断 NF-κB 通路的激活,防止 "细胞因子风暴 "的发生;促进 Nrf2 的激活,增加抗氧化分子和酶的表达;激活钾通道;阻断 Na+/K+-ATP 酶,促进电解质的吸收。在胰腺中,H 2 S 可调节胰岛素分泌,并在胰岛素反应组织的胰岛素敏感性调节中发挥重要作用。它能抑制葡萄糖摄取和糖原累积,这对糖尿病至关重要。在脂肪组织中,H 2 S 促进脂肪生成,抑制脂肪分解,调节 2 型糖尿病患者体内脂肪连素和 MCP-1 的分泌。在神经组织中,H2 S 可作为神经调节剂,增加 GABA 的表达,诱导 Ca2+ 浓度增加,参与长期电位、神经递质调节,影响 NADPH 水平,并发挥表观遗传效应。了解 H2 S 的作用可能对开发治疗各种疾病的有效策略至关重要。
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Hydrogen sulfide: biological and pathochemistry
Hydrogen sulfide (H2S) belongs to the family of «gasotransmitters» can by synthesized by enzymatic systems and also formed non-enzymatically. At physiological concentrations, it regulates a range of biological functions in various organs and tissues. H2 S is involved in biochemical changes that play an important role in the pathogenesis of diseases such as cancer, COVID-19, diabetes mellitus, and neurodegenerative pathologies. In carcinogenesis, H2S influences cancer cell proliferation, inhibits cancer cell apoptosis, regulates the cell cycle, intracellular signaling pathways, stimulates angiogenesis, and autophagy of cancer cells. In lung inflammation caused by COVID-19, H2S disrupts disulfide bonds in mucus, reducing its viscosity, blocks NF-κB pathway activation, preventing the onset of a «cytokine storm», promotes Nrf2 activation, increasing the expression of antioxidant molecules and enzymes, activates potassium channels, and blocks Na+/K+-ATPase, promoting electrolyte absorption. In the pancreas, H 2 S regulates insulin secretion and plays a significant role in insulin sensitivity regulation in insulin-responsive tissues. It inhibits glucose uptake and glycogen accumulation, which is crucial in diabetes mellitus. In adipose tissue, H 2 S promotes adipogenesis, inhibits lipolysis, and regulates the secretion of adiponectin and MCP-1 in type 2 diabetes. In neural tissue, H2S acts as a neuromodulator, increases GABA expression, induces Ca2+ concentration increase, participates in long-term potentiation, neurotransmitter modulation, affects NADPH levels, and exerts epigenetic effects. Understanding the role of H2 S may be crucial in developing effective therapy strategies for various diseases.
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