艾灸足三里对化疗后骨髓抑制小鼠Notch信号通路的影响

Effect of Moxibustion at Zusanli on Notch Signaling Pathway in Mice with Myelosuppression after Chemotherapy

目的:探索艾灸足三里对化疗后骨髓抑制小鼠Notch信号通路的影响。方法:C57BL/6J小鼠移植肿瘤采用环磷酰胺(CTX)治疗建造荷瘤鼠骨髓抑制模型,观察比较正常组、空白组、模型组以及艾灸组的小鼠在治疗过程中的行为以及血液中白细胞数的变化,苏木素-伊红染色(HE)检测骨髓组织的病理变化,免疫组化检测骨髓组织中CBF-1/Suppressor of hairless/Lag(CSL)、Jagged1、Jagged2蛋白的变化,Western bloting实验检测骨髓组织中Notch1、Notch2、Notch3蛋白表达及其激活情况,实时荧光定量PCR(RT-PCR)实验检测骨髓组织中Notch1、Notch2、Notch3 mRNA表达。结果:通过艾灸足三里可使骨髓抑制模型组小鼠精神状态、行为、体质量、外周血白细胞数目以及受到破坏的骨髓组织均恢复正常,在分子水平上,艾灸足三里可使骨髓抑制模型小鼠骨髓组织中受到抑制的CSL、Jagged1、Jagged2、Notch1、Notch2、Notch3蛋白表达水平恢复至正常水平。结论:CTX可抑制荷瘤小鼠骨髓增殖和Notch信号通路,艾灸足三里可缓解CTX导致的骨髓抑制,激活骨髓中被抑制的Notch信号通路。

Objective:To explore the effect of moxibustion at Zusanli on Notch signaling pathway in mice with myelosuppression after chemotherapy.Methods:The tumors were transplanted into C57BL/6J mice,and the bone marrow suppression model of tumor-bearing mice was established by CTX treatment.The changes of behavior and blood leukocyte counts in the normal,blank,model and moxibustion groups were observed.HE examined the pathological changes of bone marrow tissue;immunohistochemistry detected CSL,Jagged1,Jagged2 protein level in bone marrow tissue.The expression of Notch1,Notch2 and Notch3 protein in bone marrow was detected by Western blotting.The expression of Notch1,Notch2 and Notch3 mRNA in bone marrow was detected by RT-PCR.Results Moxibustion Zusanli could restore the mental state,behavior,body weight,peripheral blood leukocyte count and damaged bone marrow tissue of the bone marrow suppression model to normal.At the molecular level,Moxibustion Zusanli can restore the expression levels of CBF-1/Suppressor of hairless/Lag(CSL),Jagged1,Jagged2,Notch1,Notch2 and Notch3 proteins in the bone marrow tissues of bone marrow suppression mice to normal levels.Conclusion CTX can inhibit bone marrow proliferation and Notch signaling pathway in tumor-bearing mice.Moxibustion Zusanli can alleviate bone marrow suppression induced by CTX and activate the inhibited Notch signaling pathway in bone marrow.