桃红四物汤增强顺铂化疗对肺腺癌小鼠的抑瘤作用  

The antitumor effect of cisplatin chemotherapy promoted by Taohong Siwu Decoction on mice with lung adenocarcinoma

作　　者：李白坤[1,2] 陈诗雨 吴晓红 叶明君 朱婷 朱继民[2,4] 李庆林[2,3] LI Bai-kun;CHEN Shi-yu;WU Xiao-hong;YE Ming-jun;ZHU Ting;ZHU Ji-min;LI Qing-lin(School of Traditional Chinese Medicine,Anhui University of Chinese Medicine,Hefei 230012,China;Key Laboratory of Xin'an Medicine,the Ministry of Education,Anhui University of Chinese Medicine,Hefei 230038,China;School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;School of Life Sciences,Anhui University of Chinese Medicine,Hefei 230012,China)

机构地区：[1]安徽中医药大学中医学院,安徽合肥230012 [2]安徽中医药大学新安医学教育部重点实验室,安徽合肥230038 [3]安徽中医药大学药学院,安徽合肥230012 [4]安徽中医药大学生命科学学院,安徽合肥230012

出　　处：《中国药理学通报》2023年第3期588-593,共6页Chinese Pharmacological Bulletin

基　　金：安徽省自然科学基金项目(No 2208085MH279);安徽中医药大学自然科学研究重点项目(No 2021zrzd06);安徽中医药大学人才支持计划项目(No 2022rcyb027);安徽高校自然科学研究重点项目(No KJ2019A0460,2022AH050519);新安医学教育部重点实验室开放课题(No 2020xayx05)。

摘　　要：目的研究桃红四物汤(Taohong Siwu Decoction,TSD)增强顺铂(cisplatin,DDP)化疗对肺腺癌移植小鼠的抑瘤作用。方法以鼠源肺腺癌细胞系Lewis制备鼠肺腺癌细胞移植瘤模型,设5组:正常对照、模型、TSD、DDP、TSD+DDP。观察给药后移植瘤体积变化,称量移植瘤质量,免疫组化法检测移植瘤组织Ki67表达量,荧光染色法检测移植瘤TUNEL表达量,Western blot法检测移植瘤组织Bcl-2、Bax、cleaved Caspase-3、cleaved Caspase-9表达量,ELISA法测鼠血浆中D-二聚体含量。结果TSD和DDP联用明显抑制移植瘤增长,瘤组织中Ki67表达水平(28.3%±3.1%)低于DDP单用组(40.3%±2.1%)。TSD和DDP联用明显促进移植瘤的凋亡水平,TUNEL阳性率明显高于DDP单用组(41.0%±3.0%vs 30.7%±4.5%),瘤组织中Bax、cleaved Caspase-3、cleaved Caspase-9表达量也高于DDP单用组,而Bcl-2表达量则明显低于DDP单用组,且TSD与DDP在4种凋亡蛋白表达量呈现明显的交互作用(P<0.05)。TSD和DDP联用组血浆中D-二聚体含量(188.50±28.46)μg·L^(-1)明显降低,且与DDP单用组(269.80±35.92)μg·L^(-1)间的差异有统计学意义(P<0.05)。结论TSD可能通过改善肿瘤高凝状态而增强DDP化疗对肺腺癌移植瘤的抑制作用。Aim To study the antitumor effect of cisplatin(DDP)chemotherapy promoted by Taohong Siwu Decoction(TSD)on mice with lung adenocarcinoma mice.Methods Lewis lung carcinoma cell line was used to make homologous lung adenocarcinoma transplantation mouse model.Normal control,Model,TSD,DDP,TSD+DDP groups were set up.The change of transplanted tumor volume after administration was observed,the weight of transplanted tumor was weighed,the expression of Ki67 in transplanted tumor tissue was detected by immunohistochemistry,TUNEL was detected by fluorescence staining,Bcl-2,Bax,cleaved Caspase-3 and cleaved Caspase-9 were detected by immunoblotting,and the content of D-dimer in plasma was measured by ELISA.Results DDP plus TSD significantly inhibited the growth of transplanted tumor.Ki67 expression in tumor tissue was lower than that in DDP group(28.3%±3.1%vs 40.3%±2.1%).The combined use of TSD and DDP significantly promoted the apoptosis level of transplanted tumor.The positive rate of TUNEL was significantly higher than that of DDP group(41.0%±3.0%vs 30.7%±4.5%).Bax,cleaved Caspase-3 and cleaved Caspase-9 expressions in tumor tissue were also higher than those of DDP group,while the expression of Bcl-2 was significantly lower than that of DDP group.Moreover,we found a significant interaction between TSD and DDP on the expression of four apoptotic proteins(P<0.05).The plasma D-dimer content in TSD+DDP group was significantly lower than that in DDP group(188.50±28.46 vs 269.80±35.92)μg·L^(-1)(P<0.05).Conclusion TSD may promote the inhibitory effect of DDP chemotherapy on transplanted lung adenocarcinoma by alleviating carcinoma hypercoagulale state.

关 键 词：肺腺癌 化疗 顺铂 高凝状态 桃红四物汤 小鼠模型 

分 类 号：R332[医药卫生—人体生理学] R289.5[医药卫生—基础医学] R734.2R979.1