首页|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

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

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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10 μg/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TGF β1、JAM3 mRNA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.
Mechanism of moxibustion on improving chemotherapy-induced neutropenia in breast cancer through TGFβ1/TSC22D1 signaling pathway
Objective:To observe the mechanism of moxibustion on improving chemotherapy-induced neutropenia(CIN)in breast cancer through transforming growth factor beta 1(TGF β1)/transforming growth factor beta stimulated clone-22 domain family protein-1(TSC22D1)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 10 μg/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 TGFβ 1,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 TGF β 1,TSC22D1,JAM3,ESAM,ICAM-1,and VCAM-1.Results:Compared with tumor control group,the mRNA and protein expressions of TGF β 1 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 TGF β1 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).Conclusion:Moxibustion could increase the adhesion function of neutrophils through the TGFβ1/TSC22D1 signaling pathway,induces neutrophils from infantile to mature,and then improves CIN of breast cancer.

MoxibustionBreast cancerChemotherapy-induced neutropenia(CIN)Transforming growth factor beta 1(TGF β1)Transforming growth factor beta stimulated clone-22 domain family protein 1(TSC22D1)

乔宇、薛晓红、杨茗橘、李思雨、曹璐璐、高超、张惜音、吴焕淦、季亚婕

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上海市针灸经络研究所,上海 200030

上海中医药大学附属岳阳中西医结合医院,上海 200437

上海中医药大学附属曙光医院,上海 200021

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

国家自然科学基金项目上海市针灸临床医学研究中心促进市级医院临床技能与临床创新能力三年行动计划上海市科学技术委员会科技计划项目上海市科学技术委员会科技计划项目国家中医药领军人才"岐黄学者"

8200444620MC1920500SHDC2020CR405722Y1192300020Y21901100

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(9)