"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OA北大核心CSTPCDMEDLINE
Mechanism of acupuncture and moxibustion in ameliorating liver injury induced by cisplatin by regulating IRE-1 signaling pathway
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.
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.
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
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河南中医药大学针灸推拿学院,郑州 450046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
针灸顺铂肝损伤内质网应激肌醇需求酶-1α
Acupuncture and moxibustionCisplatinLiver injuryEndoplasmic reticulum stressIRE-1α
《针刺研究》 2024 (007)
686-692 / 7
国家自然科学基金青年基金项目(No.81804196);河南省省级科技研发计划联合基金项目(优势学科培育类)(No.222301420077);河南中医药大学2023年度研究生科研创新项目(No.2023KYCX074)
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