首页|"扶正益肝"针灸穴方基于肌醇需求酶1信号通路改善顺铂致小鼠肝损伤的机制

"扶正益肝"针灸穴方基于肌醇需求酶1信号通路改善顺铂致小鼠肝损伤的机制

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目的:基于与肝细胞内质网应激反应相关的肌醇需求酶(IRE)-1信号通路,探讨"扶正益肝"针灸穴方改善顺铂(DDP)所致小鼠肝损伤的作用机制.方法:昆明种小鼠随机分为空白组、模型组、针刺组和艾灸组,每组10只.一次性腹腔注射DDP(10 mg/kg)复制肝损伤模型.针刺组和艾灸组分别选取"大椎""肝俞""肾俞""足三里"进行针刺、艾灸治疗,每次6 min,1次/d,治疗7 d.采用TUNEL染色检测肝细胞凋亡情况,免疫组织化学法、Western blot法检测肝组织中磷酸化(p)-IRE-1α、葡萄糖调节蛋白(Grp)78、半胱氨酸天冬氨酸蛋白酶(Caspase)-12的表达,实时荧光定量PCR法检测肝组织中Grp78、Caspase-12 mRNA表达.结果:与空白组比较,模型组小鼠肝细胞凋亡率升高(P<0.05),肝组织中p-IRE-1α、Grp78、Caspase-12阳性表达和蛋白表达升高(P<0.05),Grp78、Caspase-12 mRNA相对表达量升高(P<0.05).与模型组比较,针刺组、艾灸组小鼠肝细胞凋亡率降低(P<0.05),肝组织中p-IRE-1α、Grp78、Caspase-12阳性表达和蛋白表达降低(P<0.05),Grp78、Caspase-12 mRNA相对表达量降低(P<0.05).结论:"扶正益肝"针灸穴方可能通过调控IRE-1信号通路,抑制内质网应激的过度激活,减轻肝细胞凋亡,从而改善DDP化疗所致的肝损伤.
Mechanism of acupuncture and moxibustion in ameliorating liver injury induced by cisplatin by regulating IRE-1 signaling pathway
Objective To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury in cisplatin(DDP)induced liver injury model mice by observing the changes of inositol-requiring enzyme(IRE)-1 signaling pathway.Methods Forty KM mice were randomly divided into control,model,acupuncture and moxibustion groups,with 10 mice in each group.The liver injury model was replicated by intraperitoneal injection of DDP(10 mg/kg).In the acupuncture group and the moxibustion group,acupuncture and moxibustion were performed at"Dazhui"(GV14),and bilateral"Ganshu"(BL18),"Shenshu"(BL23),and"Zusanli"(ST36),respectively for 6 min,once per day for 7 d.The apoptosis of hepatocytes was detected by TUNEL staining.The expression of phosphorylation(p)-IRE-1α,glucose-regulated protein(Grp)78 and cysteine aspartic protease(Caspase)-12 in liver tissue were detected by immunohistochemistry and Western blot,respectively.The expression levels of Grp78 and Caspase-12 mRNA in liver tissue were detected by quantitative real-time PCR.Results Compared with the control group,the apoptosis rate of hepatocytes was increased(P<0.05),the positive expression and protein expression of p-IRE-1α,Grp78,and Caspase-12 were increased(P<0.05),the expression levels of Grp78 and Caspase-12 mRNA were increased(P<0.05)in the model group.Compared with the model group,all these indicators showed opposite trends(P<0.05)in the acupuncture and moxibustion groups.Conclusion Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating IRE-1 signaling pathway,inhibiting the excessive activation of endoplasmic reticulum stress,and reducing liver cell apoptosis.

Acupuncture and moxibustionCisplatinLiver injuryEndoplasmic reticulum stressIRE-1α

于冬冬、王建明、韩乐、杜雪源、晁利芹、张欢欢、吴昊、王晴晴、刘文姣

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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 450008

河南中医药大学中医学院,郑州 450001

河南中医药大学医学院,郑州 450046

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针灸 顺铂 肝损伤 内质网应激 肌醇需求酶-1α

国家自然科学基金青年基金项目河南省省级科技研发计划联合基金项目(优势学科培育类)河南中医药大学2023年度研究生科研创新项目

818041962223014200772023KYCX074

2024

针刺研究
中国中医研究院针灸研究所,中国针灸学会

针刺研究

CSTPCD北大核心
影响因子:1.656
ISSN:1000-0607
年,卷(期):2024.49(7)
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