冷大气压等离子体诱导的交变电场对白细胞介素-6结构及功能的影响

Effect of alternating electric field induced by cold atmospheric plasma on conformation and function of interleukin-6

冷大气压等离子体(cold atmospheric plasma,CAP)由于其具有“选择性”杀伤癌细胞的效果,而被认为是一种极具潜力的癌症治疗手段.CAP可以通过降低关键炎症因子白细胞介素-6(interleukin-6,IL-6)的表达,抑制肿瘤炎症反应并激活免疫系统.然而CAP携带的强交变电场对IL-6构象及功能的影响仍缺乏了解.本文采用分子动力学方法,模拟了不同频率及强度的交变电场对IL-6构象及其与受体对接过程的影响.结果表明,当电场频率小于30 MHz且电场强度大于0.5 V/nm时,IL-6的平均偶极矩增大,长螺旋间维持稳定的盐桥断裂,α螺旋数量减少,从而影响了IL-6与其受体的结合,对其发挥正常生物效应机制产生潜在影响.本文从微观层面上解释了CAP诱导的电场通过IL-6影响相关生物学效应的内部相互作用机制,并为实际应用CAP治疗肿瘤炎症的参数选取、探索有效的癌症治疗策略提供重要的理论依据.

Cold atmospheric plasma(CAP)is considered to be a very promising cancer treatment method due to its“selective”killing effect on cancer cells.The CAP can inhibit tumor inflammatory responses and activate the immune system by reducing the expression of the key inflammatory factor Interleukin-6(IL-6).However,the influence of the strong alternating electric field induced by CAP on the conformation and function of IL-6 remains unclear.In this study molecular dynamics simulation is used to investigate the effects of alternating electric fields with different frequencies and intensities on the conformation of IL-6.We statistically analyze the root mean square fluctuations,root mean square deviation,secondary structural alterations,and dipole moment changes of IL-6 under different electric field parameters.Furthermore,molecular docking is utilized to assess the influence on the receptor-binding process.The results show that when the electric field frequency is below 30 MHz and the intensity exceeds 0.5 V/nm,the average dipole moment of IL-6 increases,leading to changes in the rigid regions at the C-terminus which maintain structural stability.Specifically,the salt bridges that stabilize the long helices rupture,and the number ofα-helices decreases.The docking outcomes reveal that the distance between the key binding residues of the conformationally altered IL-6 and its receptor increases,thereby disrupting the normal binding process and potentially impairing its normal biological functionality.This study explains the internal interaction mechanism of CAP-induced electric fields affecting IL-6-related biological effects at the micro level,and provides important theoretical basis for optimizing parameters in the practical application of CAP in tumor inflammation treatment and the development of effective cancer therapy strategies.