桦褐孔菌提取物对阿托伐他汀致小鼠肝损伤的保护作用  

Protective Effects of Inonotus obiquus Extract on Atorvastatin-induced Liver Injury in Mice

作　　者：李毅 李建宽[2] 杨红 李青山 LI Yi;LI Jiankuan;YANG Hong;LI Qingshan(Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation,College of Traditional Chinese Medicine(TCM)and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 030619,China;School of Pharmaceutical Science,Shanxi Medical Universiry,Jinzhong 030619,China)

机构地区：[1]山西中医药大学中药与食品工程学院,基于炎性反应的重大疾病创新药物山西省重点实验室,山西晋中030619 [2]山西医科大学药学院,山西晋中030619

出　　处：《中国兽医杂志》2024年第2期18-26,共9页Chinese Journal of Veterinary Medicine

基　　金：山西省中医药强省计划项目(202105D121011)。

摘　　要：为了研究桦褐孔菌提取物(IOE)对阿托伐他汀(ATO)致小鼠药物性肝损伤的保护作用及机制,本试验将48只雄性昆明系小鼠随机分为6个组:对照组、模型组、IOE低、中、高剂量组[100、200、400 mg/(kg·bw)]和双环醇组[200 mg/(kg·bw)],采用ATO灌胃造模。除模型组外,IOE低、中、高剂量组给予不同浓度IOE,双环醇组给予双环醇作为阳性对照药物,连续灌胃2个月后,测定各组小鼠肝脏指数,检测肝功能、肝脏抗氧化应激和抗炎指标,观察各组小鼠的肝脏组织病理学特征,并检测丝裂原活化蛋白激酶(MAPK)信号通路相关蛋白表达水平。结果显示,与对照组比较,模型组小鼠肝脏指数极显著升高(P<0.01);血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)水平极显著升高(P<0.01);肝脏组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活性极显著降低(P<0.01),丙二醛(MDA)含量极显著升高(P<0.01);c-Jun氨基末端激酶(JNK)和丝裂原活化蛋白激酶(p38)磷酸化水平极显著升高(P<0.01),B细胞淋巴瘤因子(Bcl-2)相关蛋白X(Bax)蛋白表达极显著升高(P<0.01),Bcl-2蛋白表达无差异(P>0.05)。与模型组比较,IOE高剂量组小鼠血清中ALT、AST、TNF-α、IL-1β和IL-6水平极显著降低(P<0.01),ALP水平显著下降(P<0.05);肝脏组织中SOD、CAT和GSH-Px活性极显著升高(P<0.01),MDA含量显著降低(P<0.05)且具有剂量依赖性;JNK和p38磷酸化水平极显著降低(P<0.01),Bax蛋白表达极显著降低(P<0.01),Bcl-2蛋白表达无差异(P>0.05);与模型组相比,IOE低、中、高剂量组和双环醇组小鼠肝脏病理损伤明显减轻。结果表明,IOE对ATO致小鼠药物性肝损伤具有保护作用,其机制可能与提高体内抗氧化酶活性、抑制炎症和细胞凋亡以及激活MAPK信号通路有关。本试验结果可为预防和治疗临床长To investigate the protective effects and mechanisms of Inonotus obliquus extract(IOE)on atorvastatin(ATO)-induced drug-induced liver injury in mice,48 male Kunming mice were randomly divided into six groups:Control group,Model group,IOE low-,medium-,high-dose groups[100,200,400 mg/(kg·bw)],and Bicyclol group[200 mg/(kg·bw)].ATO was administered by gavage to induce the model.Except for the Model group,IOE low-,medium-,high-dose groups received different concentrations of IOE,the Bicyclol group was given bicyclol as a positive control drug.After continuous gavage for 2 months,the liver index of mice in each group was determined;the liver function,hepatic oxidative stress,and anti-inflammatory indicators were detected;the histopathological characteristics of mouse liver tissues in each group were observed;and the expression levels of proteins related to the mitogen-activated protein kinase(MAPK)signaling pathway were measured.The results showed that compared with the Control group,the liver index of mice in the Model group extremely significant increased(P<0.01);serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)levels extremely significant increased(P<0.01);the activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)in liver tissues extremely significant decreased(P<0.01),malondialdehyde(MDA)content extremely significant increased(P<0.01);phosphorylation levels of c-Jun N-terminal kinase(JNK)and mitogen-activated protein kinase(p38)extremely significant increased(P<0.01),B-cell lymphoma-2(Bcl-2)-associated protein X(Bax)protein expression extremely significant increased(P<0.01),and Bcl-2 protein expression showed no difference(P>0.05).Compared with the Model group,the High-dose IOE group showed extremely significant decreases in serum ALT,AST,TNF-α,IL-1β,and IL-6 levels(P<0.01),and significant decreases in ALP levels(P<0.05);the activities of SOD,CAT,and GSH

关 键 词：桦褐孔菌 阿托伐他汀 药物性肝损伤 氧化应激 

分 类 号：R284[医药卫生—中药学]