异质金属调控下医用镁的氢气释放对肿瘤细胞的影响

Effect of Hydrogen Released from Biomedical Magnesium Regulated by Dissimilar Metals on Tumor Cell

目的通过异质金属引发的电偶腐蚀效应,引起高纯镁在不同程度上的氢气释放,达到不同程度的抗肿瘤效应。方法将高纯镁(Mg)与镁合金(AZ91)、纯钛(TA2)、不锈钢(316L)分别连接。在37℃水浴环境、PBS溶液环境中,通过电化学工作站测定了高纯镁的开路电位和极化曲线,同时,通过浸泡试验测定了析氢曲线。最后,在体外研究了不同异质金属调控下,高纯镁的不同氢气释放量对Cal-62肿瘤细胞系的生物学效应,包括氢气对肿瘤细胞的抑制增殖、促进凋亡和阻滞细胞周期的影响。结果三种金属都引起了不同程度的极化作用,且极化作用越强,高纯镁的开路电位、腐蚀电位和腐蚀电流密度越大,试样的析氢量也随之增多。氢气释放48 h后,显著抑制了Cal-62肿瘤细胞的增殖,抑制率最高可达55%。一方面,氢气能够促进肿瘤细胞凋亡;另一方面,氢气使肿瘤细胞G0/G1期比例增加,S期比例减少,将肿瘤细胞周期阻滞在G0/G1期,且随着氢气释放量增多,凋亡和阻滞周期的作用更为显著。结论异质金属调控下,能够通过引起高纯镁不同程度的腐蚀,加速释放产生更多的氢气,达到更为显著的抗肿瘤效应。

Different degrees of anti-tumor effect by hydrogen release from high purity magnesium(Mg)through galvanic corrosion induced by dissimilar metals can be achieved.High-purity Mg was connected to Mg alloy AZ91,pure titanium TA2 and stainless steel 316L respectively.The open circuit potential and polarization curve of high-purity Mg were measured by electrochemical workstation in PBS solution under 37℃water bath condition,and hydrogen evolution curve was measured by immersion experiment under the same conditions.Finally,the biological effects of different amounts of hydrogen released by high-purity Mg under the regulation of dissimilar metals on Cal-62 tumor cell line were studied in vitro,including the effects of hydrogen on proliferation,apoptosis and cycle of tumor cells.It was found that the three metals cause different degrees of polarization.The open circuit potential,corrosion potential and corrosion current density of high purity Mg all increased with the increase of polarization,which caused more significant hydrogen evolution in the meantime.48 hours after the release of hydrogen,the proliferation of Cal-62 tumor cells was significantly inhibited,up to 55%.On the one hand,hydrogen could promote apoptosis of tumor cells.On the other hand,hydrogen could increase the proportion of cells in G0/G1 phase and decrease the proportion of cells in S phase,arresting the cell cycle of tumor cells in G0/G1 phase.As the amount of hydrogen released increased,the effects of promoting apoptosis and arresting the cell cycle were more significant.Under the control of these three dissimilar metals,Mg can accelerate the release of more hydrogen through different degrees of corrosion,and achieve a more significant anti-tumor effect.