雌激素受体α在平滑肌收缩过程中钙转运的作用
The role of estrogen receptor alpha on calcium transport during smooth muscle contractions
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中文总结 AI 辅助
本研究通过扩展平滑肌细胞钙信号数学模型，结合数值模拟等分析，揭示雌激素受体α主要作为定量调节剂影响平滑肌钙转运，为激素依赖性细胞生理模型奠定基础。
中文摘要 AI 辅助
生殖激素调节人类整个生命周期中的多种生理过程，其中雌激素在月经周期中变化显著，被广泛应用于避孕药和激素替代疗法。尽管雌激素具有重要生理意义，但鲜有实验研究，数学模型更是极少明确探究雌激素如何调节平滑肌功能。由于平滑肌分布于血管、气道、子宫及其他多个器官，了解雌激素对平滑肌的影响对深化对终身健康中性别差异的认识具有重要意义。本研究扩展了已建立的平滑肌细胞钙信号数学模型，纳入雌激素对细胞内钙转运通路的依赖性调节，随后通过数值模拟、全局敏感性分析和数值分岔分析，量化雌激素对细胞内钙动力学及由此产生的稳态和振荡行为的影响。结果表明，生理相关的雌激素变化会改变细胞内钙浓度，但不会改变潜在的分岔结构和定性动力学，提示雌激素主要作为平滑肌钙信号的定量调节剂发挥作用，本研究也为未来激素依赖性细胞生理学的机制模型奠定了基础。
英文摘要
Reproductive hormones regulate a wide range of physiological processes throughout the human lifespan. Estrogen, in particular, varies substantially across the menstrual cycle and is widely used in contraceptives and hormone replacement therapies. Despite its physiological importance, few experimental studies and even fewer mathematical models explicitly investigate how estrogen regulates smooth muscle function. As smooth muscle lines our blood vessels, airways, uterus, and several other organs, understanding how estrogen impacts smooth muscle is important to improving the understanding of sex differences in lifelong health. Here we extend an established mathematical model of smooth muscle cell calcium signalling to incorporate estrogen-dependent modulation of intracellular calcium transport pathways. Numerical simulations, global sensitivity analysis, and numerical bifurcation analysis are then used to quantify the influence of estrogen on intracellular calcium dynamics and the resulting steady-state and oscillatory behaviours. Our results demonstrate that physiologically relevant changes in estrogen shift intracellular calcium concentrations while leaving the underlying bifurcation structure and qualitative dynamics largely unchanged, suggesting that estrogen acts primarily as a quantitative modulator of smooth muscle calcium signalling. This work also serves to establish a foundation for future mechanistic models of hormone-dependent cell physiology.
