摘要
目的通过观察针灸对顺铂(Cisplatin,DDP)所致肝损伤小鼠与肝细胞炎症反应相关的肿瘤坏死因子-α(TNF-α)、Toll样受体4(TLR4)和核因子-κB(NF-κB)表达含量的变化,以及血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)和谷氨酸脱氢酶(GLDH)活性变化,并结合小鼠肝脏病理变化,阐释针灸对DDP引起肝损伤小鼠的作用机制。方法选用SPF雄性KM小鼠,随机分为4组,按照10 mL·kg^(-1)空白组腹腔注射0.9%NaCl溶液,其余3组按照体质量腹腔注射同剂量DDP溶液,24 h后模型成功。干预组采用“大椎”“肝俞”“肾俞”“足三里”,分别给予针刺和艾灸干预,其余两组陪同固定不干预,每天1次,持续5天。断食1天后取材,生化检测血清中ALT、AST、GLDH含量,Western blot测定肝脏中TNF-α、TLR4、NF-κB蛋白表达含量。结果与空白组比,模型组血清中ALT、AST、GLDH活性增高,肝脏中TNF-α、TLR4、NF-κB蛋白表达升高,均有统计学意义(P<0.05)。与模型组比,针刺组和艾灸组ALT、AST、GLDH活性和TNF-α、TLR4、NF-κB蛋白表达均降低,均有统计学意义(P<0.05)。与针刺组比,艾灸组血清中ALT、AST活性降低,GLDH活性升高,TNF-α蛋白表达降低,但均无统计学意义(P>0.05),TLR4、NF-κB蛋白表达降低,有统计学意义(P<0.05)。结论针灸可能通过抑制TNF-α、TLR4的过度表达,从而降低NF-κB过度表达,减少炎症因子的过度释放,从而减轻DDP小鼠肝脏炎症的发生,降低DDP对肝脏产生的毒副作用,对肝脏起到有效的保护作用。
Objective To observe the changes of tumor necrosis factor-α(TNF-α),Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)expression levels related to hepatocyte inflammation in mice with liver injury induced by Cisplatin(DDP).And the activity changes of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and glutamate dehydrogenase(GLDH)in serum,combined with the pathological changes of mouse liver,to explain the mechanism of acupuncture and moxibustion on DDP induced liver injury in mice.Methods SPF male Kunming mice were randomly divided into 4 groups.The blank group was intraperitoneally injected with 0.9%NaCl solution according to 10 mL·kg^(-1),and the other 3 groups were intraperitoneally injected with the same dose of DDP solution according to body weight.In the intervention group,"Dazhui(DU14)","Ganshu(BL18)","Shenshu(BL23)"and"Zusanli(T36)"were given acupuncture and moxibustion intervention respectively,while the other two groups were accompanied and fixed without intervention,once a day for 5 days.The serum ALT,AST and GLDH levels were detected by biochemical analysis.The protein expressions of TNF-α,TLR4 and NF-κB in liver were determined by Western blot analysis.Results Compared with the blank group,the activities of ALT,AST and GLDH in serum of the model group were increased,and the protein expressions of TNF-α,TLR4 and NF-κB in liver were increased,with statistical significance(P<0.05).Compared with the model group,the activities of ALT,AST and GLDH and the protein expressions of TNF-α,TLR4 and NF-κB in the acupuncture and moxibustion groups were significantly decreased(P<0.05).Compared with the acupuncture group,the activities of ALT and AST in serum of the moxibustion group were decreased,the activity of GLDH was increased,the protein expression of TNF-αwas decreased,but there was no statistical significance(P>0.05),the protein expression of TLR4 was decreased,and the protein expression of NF-κB was decreased,and there was statistical significance(P<0.05).Conclusion Acupuncture and moxibustion may reduce the overexpression of TNF-αand TLR4,thereby reducing the overexpression of NF-κB and the excessive release of inflammatory factors,so as to reduce the occurrence of liver inflammation in DDP mice,reduce the toxic and side effects of DDP on the liver,and play an effective protective role on the liver.
作者
王文哲
魏星宇
于冬冬
杜雪源
张晨
王建明
韩乐
Wang Wenzhe;Wei Xingyu;Yu Dongdong;Du Xueyuan;Zhang Chen;Wang Jianming;Han Le(College of Acupuncture and Massage,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China;The Third Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,China;College of Traditional Chinese Medicine,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第3期1055-1060,共6页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会青年基金项目(81804196):基于Notch信号通路及肝脏超微结构的针灸拮抗顺铂化疗小鼠肝损伤的机制研究,负责人:于冬冬
河南省科学技术厅河南省省级科技研发计划联合基金(优势学科培育类)(222301420077):基于JNK/c-Jun凋亡通路针灸拮抗DDP肝损伤的机制研究,负责人:于冬冬
河南中医药大学博士科研启动项目(RSBSJJ2019-16):针灸拮抗CTX化疗所致骨髓损伤的作用机制,负责人:杜雪源
关键词
针灸
顺铂
肝损伤
肿瘤坏死因子-α
TOLL样受体4
核因子-ΚB
Acupuncture and moxibustion
Cisplatin
Liver injury
Tumor necrosis factor-α
Toll-like receptor 4
Nuclear factor kappa-B predominate
作者简介
通讯作者:于冬冬,副教授,硕士研究生导师,博士,主要研究方向:针灸抗放化疗毒副作用及脏器损伤的研究。
