摘要
目的探讨复方药物翁沥通(WLT)对顺铂(cisplatin,CDDP)诱导肝细胞损伤的保护作用。方法通过CDDP(80μmol/L)处理小鼠肝细胞系BNL CL.2,构建细胞损伤模型,并进行实验分组,CDDP组仅造模,WLT组(1 g/L WLT干预)和WLT+CDDP联合用药组(CDDP作用的同时给予1 g/L WLT);并另设对照组(正常培养)。通过CCK-8、PI染色、结晶紫染色、Western blotting、活性氧(ROS)检测和细胞凋亡分析,评价复方药物WLT对CDDP介导肝细胞损伤的保护作用。结果与对照组相比,CDDP组的细胞死亡数量增多(P<0.001),而WLT组未造成细胞毒性;与CDDP组细胞收缩形态相比,WLT+CDDP联合用药组的肝细胞形态改善,无明显收缩,PI染色阳性比例降低,同时,结晶紫染色结果显示,与CDDP组比较,联合用药组细胞数量较多,也体现了WLT对CDDP介导肝损伤的保护作用。在CDDP干预下,细胞凋亡相关蛋白Cleaved Caspase-3表达增加,而联合用药组Cleaved Caspase-3表达降低,抗凋亡蛋白Bcl-2表达增加。此外,与CDDP组比较,联合用药组ROS产生减少[DCFH-DA染色阳性率(%):56.20±1.65 vs.44.57±0.31]及细胞凋亡比例下降[早期、晚期凋亡细胞比例(%):43.60±0.44 vs.19.57±0.78;33.30±1.02 vs.14.83±0.57]。结论复方药物WLT对CDDP介导的肝细胞损伤具有保护作用,该药物可能在急性肝损伤模型中也具有重要的应用价值。
Objective To investigate the protective effect of the compound drug Weng-Li-Tong(WLT)against cisplatin(CDDP)-induced hepatocyte injury.Methods A cellular injury model was established by treating murine hepatocyte line BNL CL.2 with CDDP(80μmol/L).Experimental groups were divided as follows:CDDP group(modeling only),WLT group(intervention with 1 g/L WLT),WLT+CDDP group(co-administration of CDDP and 1 g/L WLT),and a control group(normal culture).The protective effect of the compound drug WLT on CDDP-mediated hepatocyte injury was evaluated using CCK-8 assay,PI staining,crystal violet staining,Western blotting,reactive oxygen species(ROS)detection,and apoptosis analysis.Results Compared with the control group,the number of dead cells increased significantly(P<0.001)in the CDDP group,but no cytotoxicity was observed in the WLT group.The hepatocyte morphology in the WLT+CDDP group showed improvement with no obvious shrinkage compared to the CDDP group,as evidenced by the reduced proportion of PI-positive cells.Crystal violet staining results also indicated a higher cell count in the WLT+CDDP group than in the CDDP group,suggesting the protective effect of WLT against CDDP-mediated liver injury.Under CDDP intervention,the expression of the apoptosis-related protein Cleaved Caspase-3 increased.However,in the WLT+CDDP group,the expression of Cleaved Caspase-3 decreased,while the expression of the anti-apoptotic protein Bcl-2 increased.Additionally,compared to the CDDP group,the WLT+CDDP group showed a reduction in ROS production[DCFH-DA staining positive rate(%):56.20±1.65 vs.44.57±0.31]and a decrease in the proportion of apoptotic cells[proportion of early and late apoptotic cells(%):43.60±0.44 vs.19.57±0.78;33.30±1.02 vs.14.83±0.57].Conclusion The compound drug WLT exhibits a protective effect against CDDP-mediated hepatocyte injury,suggesting potential therapeutic value in acute liver injury models.
作者
闫亮文
李欣妍
徐嘉怡
白锋云
袁芬越
孙颖
刘朋飞
YAN Liangwen;LI Xinyan;XU Jiayi;BAI Fengyun;YUAN Fenyue;SUN Ying;LIU Pengfei(National and Local Joint Engineering Research Center for Biological Diagnosis and Treatment,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004;Shaanxi Dongtai Pharmaceutical Co.,LTD.,Xianyang 712031,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2024年第5期815-821,共7页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金项目(No.82370585)
陕西省创新能力支撑计划(No.2023KJXX-033)
陕西省重难点研发计划(No.2022-LL-JB-30)
西安市科技计划项目(No.23YXYJ0125)
西安交通大学医学“基础-临床”融合创新项目(No.YXJLRH2022058)。
关键词
翁沥通
顺铂
肝损伤
细胞凋亡
氧化损伤
Weng-Li-Tong
cisplatin
hepatocyte injury
apoptosis
oxidative damage
