生物可降解镁对人胆管癌细胞和小鼠H22肿瘤抑制作用研究  

The inhibition effect of biodegradable magnesium on human bile duct carcinoma cells and mouse H22 tumors

作　　者：李天 刘冲 何金瞳 张丹阳 隋凯达 张洲博 邵海波[1] LI Tian;LIU Chong;HE Jintong;ZHANG Danyang;SUI Kaida;ZHANG Zhoubo;SHAO Haibo(Department of Interventional Radiology,First Affiliated Hospital of China Medical University,Shenyang,Liaoning Province 110001,China)

机构地区：[1]中国医科大学附属第一医院介入科,沈阳110001

出　　处：《介入放射学杂志》2021年第8期792-798,共7页Journal of Interventional Radiology

基　　金：国家自然科学基金面上项目(82072037、81771944);沈阳市高层次人才支持计划项目(RC170048)。

摘　　要：目的评价可降解金属镁对人胆管癌细胞(RBE)和小鼠H22肿瘤的抑制作用。方法RBE细胞分别与纯镁和钛合金第1、3、5天浸提液共培养,细胞计数试剂盒(CCK)-8检测细胞毒性,流式细胞仪分析细胞凋亡。采用H22荷瘤小鼠模型,分别植入纯镁、钛合金后,于第3、6、9、12、15天测量肿瘤重量和体积变化,并通过钼靶X线摄影观察金属在体内降解情况。脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色和免疫组化染色检测细胞凋亡和相关蛋白表达水平。结果第1、3、5天,纯镁浸提液和钛合金浸提液对RBE细胞抑制率分别为24.7%、60.2%、70.7%和-3.1%、1.3%、1.0%,差异均有统计学意义(P<0.05);细胞凋亡率分别为13.8%、33.8%、46.7%和6.1%、7.1%、5.6%,差异均有统计学意义(P<0.05)。随着时间推移,纯镁在小鼠H22肿瘤中可部分降解。纯镁组肿瘤生长受到抑制,第9、12、15天平均体积(5.6 cm^(3)、8.2 cm^(3)、11.2 cm^(3))均显著低于钛合金组(11.4 cm^(3)、18.0 cm^(3)、21.7 cm^(3))(P<0.05)。纯镁组、钛合金组凋亡细胞比率分别为9.7%、5.3%(P<0.05),纯镁组小鼠肿瘤组织碳酸酐酶(CA)Ⅸ蛋白表达与钛合金组相比显著降低(P<0.05),其上游蛋白低氧诱导因子(HIF)-1α虽有下降,但差异无统计学意义(P>0.05)。结论可降解金属镁可抑制RBE细胞和小鼠H22肿瘤生长。Objective To evaluate the inhibition effect of biodegradable magnesium on human bile duct carcinoma cells(RBE) and mouse H22 tumors. Methods RBE cells were separately co-cultured with pure magnesium and titanium alloys in the 1 st, 3 rd and 5 th day extract solution. Cell counting kit-8(CCK-8)was used to detect cytotoxicity and flow cytometry was used to analyze cell apoptosis. The pure magnesium and titanium alloy was separately implanted into H22 tumor-bearing mouse models, the changes of tumor weight and tumor volume were separately calculated at post-implantation 3, 6, 9, 12 and 15 days.Radiography with molybdenum target tube was performed to observe the degradation of the metals in vivo.TUNEL staining and immunohistochemical staining were adopted to detect apoptosis and related protein expression levels. Results On the 1st, 3rd, 5th day, the RBE cell inhibition rates in the pure magnesium group and titanium alloy group were 24.7%, 60.2%, 70.7% and-3.1%, 1.3%, 1.0% respectively, the differences between the two groups were statistically significant(P<0.05);the apoptosis rates in the pure magnesium group and titanium alloy group were 13.8%, 33.8%, 46.7% and 6.1%, 7.1%, 5.6% respectively, the differences between the two groups were statistically significant(P<0.05). With the time passing, the biodegradable magnesium in mice H22 tumors become partially degraded. Tumor growth was inhibited in the pure magnesium group, and the average tumor volumes at the 9th, 12th and 15th day were 5.6 cm^(3), 8.2 cm^(3) and 11.2 cm^(3) respectively,which were remarkably lower than 11.4 cm^(3), 18.0 cm^(3) and 21.7 cm^(3) respectively in the titanium alloy group(P<0.05). The proportion of apoptotic cells in the pure magnesium group and titanium alloy group were 9.7% and 5.3% respectively(P<0.05). The expression level of carbonic anhydrase Ⅸ(CAⅨ) protein in tumor tissue in the pure magnesium group was strikingly lower than that in the titanium alloy group(P<0.05). The expression of upstream protein hypoxia-inducible factor-1α(

关 键 词：可降解金属镁 胆管癌 小鼠H22肿瘤 细胞凋亡 

分 类 号：R735.8[医药卫生—肿瘤]