首页|顺铂致肝损伤小鼠Notch信号通路差异基因筛选及针灸对其调控的研究

顺铂致肝损伤小鼠Notch信号通路差异基因筛选及针灸对其调控的研究

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目的 通过筛选顺铂(Cisplatin,DDP)致肝损伤小鼠肝组织中Notch信号通路显著性差异基因,探讨针灸改善肝损伤的作用机制。方法 雄性KM小鼠随机分成空白组、模型组、针刺组、艾灸组、阻断剂针刺组、阻断剂艾灸组,每组10只。空白组以10 mg·kg-1剂量腹腔注射0。9%NaCl溶液,其余各组腹腔注射同等剂量的DDP溶液,24 h后模型成功。针刺组、阻断剂针刺组取"大椎"和双侧"肝俞""肾俞""足三里"干预,艾灸组、阻断剂艾灸组取相同腧穴干预,阻断剂组均于治疗前30 min腹腔注射同等剂量的DAPT。连续干预5天,于第6天取肝脏左外侧叶备检DEGseq、免疫组化以及透射电镜。结果 DEGseq初步筛选出57个与Notch信号通路相关差异基因,7个热点基因Notch1、Hes1、Adam17、Lfng、Numb、Hdac1、Notch2与肝损伤关系密切。免疫组化法对7个热点基因进一步筛选,与空白组比,模型组中Notch1、Hes1、Adam17、Lfng、Numb、Notch2、Hdac1蛋白含量上调,差异有统计学意义(P<0。05);与模型组比,其余4组中Notch1、Hes1、Adam17、Lfng蛋白含量均降低,差异有统计学意义(P<0。05);Numb、Hdac1、Notch2各组间差异无统计学意义(P>0。05)。超微病理示针灸对损伤的肝细胞具有明显的修复作用,且优于阻断剂组。结论 针刺和艾灸可能通过良性调节与Notch信号通路显著性相关的差异基因Notch1、Hes1、Adam17、Lfng的表达,抑制Notch信号通路异常激活,并能改善受损的肝细胞微观结构,减轻DDP化疗所致肝损伤,这可能是针灸减轻DDP致肝损伤的机制之一。
Screening of Differential Genes in Notch Signaling Pathway in Cisplatin-Induced Liver Injury Mice and Its Regulation by Acupuncture and Moxibustion
Objective To investigate the mechanism of acupuncture in improving liver injury by screening the significant differential genes of the Notch signaling pathway in the liver tissue of cisplatin(DDP)-induced mice.Methods Sixty male SPF mice were randomly divided into a blank group,model group,acupuncture group,moxibustion group,blocker acupuncture group,and blocker moxibustion group.The blank group was injected with 0.9%NaCl solution intraperitoneally at a dose of 10 mg·kg-1,and the other groups were injected with the same dose of DDP solution intraperitoneally,and the model was successfully established after 24 h.The acupuncture group and blocker acupuncture group were treated with"Dazhui"(GV 14),"Ganshu"(BL 18),"Shenshu"(BL 23)and"Zusanli"(ST 36),the moxibustion group and the blocker moxibustion group were treated with the same acupoint intervention,and the blocker group was injected with the same dose of DAPT intraperitoneally 30 minutes before treatment.After 5 days of continuous intervention,the left lateral lobe of the liver was taken for DEGseq,immunohistochemistry,and transmission electron microscopy to observe the ultrastructure of the liver on the 6th day.Results DEGseq preliminarily screened 57 differential genes related to the Notch signaling pathway,and 7 hotspot genes Notch1,Hes1,Lfng,Adam17,Numb,Hdac1,and Notch2 were closely related to liver injury.Compared with the blank group,the contents of Notch1,Hes1,Lfng,and Adam17 proteins in the model group were further screened by immunohistochemistry,and the differences were statistically significant(P<0.05).Compared with the model group,the contents of Notch1,Hes1,Lfng,and Adam17 proteins in the remaining four groups were reduced,with statistically significant differences(P<0.05).There was no significant difference between the Numb,Hdac1,and Notch2 groups(P>0.05).Pathological acupuncture showed that acupuncture had an obvious repair effect on the structure of hepatocytes and was superior to the blocker group.Conclusion Acupuncture and moxibustion may inhibit the abnormal activation of the Notch signaling pathway by benign regulation of the expression of differential genes Notch1,Hes1,Lfng,and Adam17 are related to the significance of the Notch signaling pathway,can improve the microstructure of damaged hepatocytes and reduce liver damage caused by DDP chemotherapy,which may be one of the mechanisms for acupuncture to reduce liver damage caused by DDP.

AcupunctureCisplatinLiver injuryNotch signaling pathway

王建明、韩乐、于冬冬、杜雪源、晁利芹、范世东、王文哲、张晨、魏星宇

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河南中医药大学针灸推拿学院 郑州 450046

河南中医药大学第三附属医院 郑州 450003

河南中医药大学中医学院 郑州 450046

河南中医药大学医学院 郑州 450046

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针灸 顺铂 肝损伤 Notch信号通路

国家自然科学基金青年基金河南省科技厅优势学科培育类项目河南省卫生健康委普通课题

818041962223014200772022ZY2041

2024

世界科学技术-中医药现代化
中科院科技政策与管理科学研究所,中国高技术产业发展促进会

世界科学技术-中医药现代化

CSTPCD北大核心
影响因子:1.175
ISSN:1674-3849
年,卷(期):2024.26(2)
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