金线莲多糖调控p38MAPK信号通路改善对乙酰氨基酚诱导的小鼠急性肝损伤  

Improvement of Anoectochilus roxburghii polysaccharides on acetaminophen-induced acute liver injury in mice by inhibiting p38 MAPK signaling pathway

作　　者：吕贵杰 陈艳成 殷金可 张勋[1] 林羽[1] LYU Guijie;CHEN Yancheng;YIN Jinke;ZHANG Xun;LIN Yu(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Department of Pharmacy,the 924th Hospital of the Joint Logistics Support Force of the Chinese PLA,Guilin 541002,China)

机构地区：[1]福建中医药大学药学院,福州350122 [2]中国人民解放军联勤保障部队第924医院药剂科,桂林541002

出　　处：《中华中医药杂志》2025年第3期1386-1391,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：福建省人力资源和社会保障厅高层次人才和青年优秀人才培养资助项目(No.GBXX2024039);福建省科技厅项目(No.2019Y4009);福建省卫生健康委员会中药研究项目(No.2021zyyj59)。

摘　　要：目的:研究金线莲多糖(ARP)对对乙酰氨基酚(APAP)诱导的急性肝损伤小鼠p38丝裂原活化蛋白激酶(p38MAPK)信号通路的影响。方法:60只雄性ICR小鼠随机分成正常组,模型组(APAP,300mg/kg),ARP低、高剂量组(200、400mg/kg)和阳性药物组(乙酰半胱氨酸,600mg/kg)。小鼠连续灌胃给药7d,末次给药2h后,一次性腹腔注射APAP(300mg/kg),建立急性肝损伤模型。观察肝脏形态和病理学变化,TUNEL染色法检测小鼠肝组织细胞凋亡情况;检测各组小鼠血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,试剂盒分别测定小鼠肝组织中谷胱甘肽(GSH)、超氧化物歧化酶(SOD)的活性。ELISA法检测小鼠肝组织肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)水平;WesternBlot法检测各组小鼠肝组织中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)和p38MAPK表达。Real-timePCR检测肝脏组织中炎症因子TNF-α、IL-1β、IL-6基因表达。结果:与模型组比较,ARP给药组能有效改善肝组织病理损伤情况,且能降低肝损伤小鼠血清中ALT、AST水平(P<0.01),提高CSH和SOD的活性(P<0.05,P<0.01);同时能够抑制APAP上调的p38MAPK磷酸化水平(P<0.01),并且降低下游靶点TNF-α、IL-1β、IL-6mRNA水平(P<0.05),提高Bcl-2/Bax比值(P<0.05)。结论:ARP能有效保护APAP诱导的急性肝损伤,其机制可能与抑制APAP激活的p38 MAPK信号通路,降低炎症因子的转录水平和增强肝脏抗氧化能力有关。Objective:To explore the effects of Anoectochilus roxburghi polysaccharides(ARP)against acetaminophen(APAP)-induced acute liver injury in mice.Methods:Sixty male ICR mice were randomly divided into six groups,including control group,model group(APAP,300 mg/kg),ARP low(200 mg/kg),high(400 mg/kg)dose group,positive drug control group(NAC,600 mg/kg).The mice were given corresponding medicines for 7 days by intragastric administration and then additionally administered APAP(300 mg/kg)to induce acute liver injury.Liver morphology and pathology in mice were observed,and hepatocyte apoptosis was analyzed by TUNEL staining;the level of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the serum were examined;the content of glutathione(GSH)and superoxide dismutase(SOD)in the liver tissue were measured.Tumor necrosis levels such as factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were tested by enzyme-linked immunosorbent assay(ELISA).B-cell lymphoma-2(Bcl-2),B lymphoma-2 gene related X protein(Bax)and p38 mitogen-activated protein kinase(p38 MAPK)protein expression in liver tissues were measured by Western Blot.The liver inflammatory cytokines TNF-α,IL-1βand IL-6 were examined by Real-time PCR.Results:Compared with the model group,ARP could effectively improve the pathological of liver tissue,the mice in the ARP groups showed significant decreases in the level of ALT,AST(P<0.01),but excited remarkable increases in the content of GSH and SOD(P<0.05,P<0.01).Additionally,ARP could down-regulate p38 MAPK Phosphorylation level(P<0.01),TNF-α,IL-1βand IL-6 transcription levels(P<0.05).At the same time,the protein expression ratio of Bcl-2/Bax were greatly improved in liver tissues(P<0.05).Conclusion:ARP played a protective effect on APAP-induced acute liver injury in mice,which could be related to the enhancement of antioxidant capacity in the liver,alleviation of liver inflammation,alleviation of oxidative stress and inhabitation the p38 MAPK signaling pathway activated byAPAP.

关 键 词：金线莲多糖 对乙酰氨基酚 急性肝损伤 P38丝裂原活化蛋白激酶 

分 类 号：R285.5[医药卫生—中药学]