艾灸通过TGFβ1/TSC22D1信号通路干预乳腺癌化疗性中性粒细胞减少症的机制  

Mechanism of moxibustion on improving chemotherapy-induced neutropenia in breast cancer through TGFβ1/TSC22D1 signaling pathway

作　　者：乔宇 薛晓红[2] 杨茗橘 李思雨 曹璐璐 高超 张惜音 吴焕淦[1] 季亚婕[1,3] QIAO Yu;XUE Xiaohong;YANG Mingju;LI Siyu;CAO Lulu;GAO Chao;ZHANG Xiyin;WU Huangan;JI Yajie(Shanghai Research Institute of Acupuncture and Meridian,Shanghai 200030,China;Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China)

机构地区：[1]上海市针灸经络研究所,上海200030 [2]上海中医药大学附属岳阳中西医结合医院,上海200437 [3]上海中医药大学附属曙光医院,上海200021

出　　处：《中华中医药杂志》2024年第9期4612-4618,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82004446);上海市针灸临床医学研究中心(No.20MC1920500);促进市级医院临床技能与临床创新能力三年行动计划(No.SHDC2020CR4057);上海市科学技术委员会科技计划项目(No.22Y11923000,No.20Y21901100);国家中医药领军人才“岐黄学者”。

摘　　要：目的:探讨艾灸通过转化生长因子β1(TGFβ1)/转化生长因子β诱导基因22结构域家族蛋白1(TSC22D1)信号通路干预乳腺癌化疗性中性粒细胞减少症的作用机制。方法:以4T1乳腺癌细胞接种于Balb/c小鼠第3对乳腺脂肪垫下构建乳腺癌小鼠模型,以环磷酰胺(CTX)溶液腹腔注射乳腺癌小鼠构建乳腺癌化疗性中性粒细胞减少症(CIN)小鼠模型。分为正常对照组、荷瘤对照组、化疗模型组、艾灸组和西药组,每组4只。艾灸组取“神阙”“足三里”“三阴交”穴进行艾灸,西药组予以人粒细胞集落刺激因子10μg/kg皮下注射。干预结束后采用HE染色观察骨髓组织病理变化,取眼眶静脉血采用磁珠吸附法提取外周血中性粒细胞,流式细胞术鉴定提取纯度,采用ELISA法检测小鼠中性粒细胞TGFβ1、TSC22D1、JAM3、ESAM、ICAM-1、VCAM-1蛋白含量,RT-qPCR法和Western Blot法检测TGFβ1、TSC22D1、JAM3、ESAM、ICAM-1、VCAM-1 mRNA和蛋白表达。结果:与荷瘤对照组比较,化疗模型组TGFβ1、JAM3 mRNA和蛋白表达显著升高(P<0.05),TSC22D1、ESAM、ICAM-1、VCAM-1 mRNA和蛋白表达显著降低(P<0.05);与化疗模型组比较,艾灸组、西药组TGFβ1、JAM3mRNA和蛋白表达显著降低(P<0.05),艾灸组TSC22D1、ESAM、ICAM-1、VCAM-1 mRNA和蛋白表达显著升高(P<0.05)。结论:艾灸通过干预TGFβ1/TSC22D1信号通路并调控JAM3、ESAM、ICAM-1、VCAM-1黏附分子的表达,增加中性粒细胞黏附功能,可能是艾灸改善乳腺癌化疗性中性粒细胞减少症的机制之一。Objective:To observe the mechanism of moxibustion on improving chemotherapy-induced neutropenia(CIN)in breast cancer through transforming growth factor beta 1(TGFβ1)/transforming growth factor beta stimulated clone-22 domain family protein-1(TSC22DI)signaling pathway.Methods:4T1 breast cancer cells were inoculated under the third pair of breast pads in Balb/c mice to establish a mouse model of breast cancer.Breast cancer mice were subjected to intraperitoneal injection of cyclophosphamide(CTX)solution to develop a breast cancer CIN mouse model.The mice were divided into normal control group,tumor-bearing control group,chemotherapy model group,moxibustion group,and western medicine group,with 4 mice in each group.In the moxibustion group,Shenque,Zusanli,and Sanyinjiao were used for moxibustion.The western medicine group received a subcutaneous injection of G-CSF 10μug/kg.After the intervention,hematoxylin-eosin(HE)staining was used to observe pathological changes in the bone marrow tissue.Peripheral blood neutrophils were extracted from the orbital vein blood using a magnetic bead adsorption method,and flow cytometry was used to identify extraction purity.The ELISA method was applied to detect the protein levels of TGFβ1,TSC22D1,JAM3,ESAM,ICAM-1,and VCAM-1 in the mice's neutrophils,while RT-qPCR and Western Blot methods were used to examine the mRNA and protein expressions of TGFβ1,TSC22DI,JAM3,ESAM,ICAM-1,and VCAM-1.Results:Compared with tumor control group,the mRNA and protein expressions of TGFβ1 and JAM3 of neutrophils in chemotherapy group were increased(P<0.05),while the mRNA and protein expressions of TSC22D1,ESAM,ICAM-1,VCAM-1 of neutrophils in chemotherapy group were decreased(P<0.05).Compared with the chemotherapy model group,the mRNA and protein expressions of TGFβ1 and JAM3 of neutrophils in the moxibustion group and western medicine group were decreased(P<0.05),while the mRNA and protein expressions of TSC22D1,ESAM,ICAM-1 and VCAM-1 of neutrophil in moxibustion group were increased(P<0.05).Concl

关 键 词：艾灸 乳腺癌 化疗性中性粒细胞减少症 转化生长因子β1 转化生长因子β诱导基因22结构域家族蛋白1 

分 类 号：R245.81[医药卫生—针灸推拿学]