摘要
目的:探讨马齿苋保护四氯化碳(CCl4)所致急性肝损伤的作用及机制。方法:60只昆明小鼠随机分为正常组、模型组、水飞蓟宾组(200 mg·kg^-1)及马齿苋高、中、低(2,1,0.5 g·kg^-1)剂量组,连续灌胃给药5 d,除正常组小鼠外,各组小鼠腹腔注射0.2%CCl4花生油溶液10 mL·kg^-1,建立急性肝损伤模型。造模23 h后,收集血清和肝脏组织。全自动分析法检测小鼠血清肝功能指标;取肝脏组织进行苏木素-伊红(HE)染色,观察肝脏病理学变化;应用转录组测序技术(RNA-seq)分析差异基因及功能富集情况,并利用实时荧光定量聚合酶链式反应(Real-time PCR)检测细胞色素P450家族成员(CYP)26A1,CYP2C37,CYP2C44,CYP2C50,CYP2C54 mRNA的表达。结果:与正常组比较,模型组小鼠的丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST),乳酸脱氢酶(LDH),总胆红素(TBIL),丙二醛(MDA)水平均明显升高(P<0.05),甘油三酯(TG)和超氧化物歧化酶(SOD)活性明显降低(P<0.05);与模型组比较,马齿苋显著降低急性肝损伤小鼠ALT,AST,TBIL,MDA水平(P<0.05),明显升高SOD活性(P<0.01),降低小鼠肝脏组织损伤程度;与正常组比较,急性肝损伤小鼠的CYP2C44,CYP2C50 mRNA表达明显降低(P<0.05);与模型组比较,马齿苋各剂量组小鼠的CYP26A1,CYP2C37,CYP2C44,CYP2C50,CYP2C54 mRNA表达明显升高(P<0.05,P<0.01)。结论:马齿苋对CCl4所致急性肝损伤具有显著的保护作用,其作用机制可能与调节细胞色素P450相关基因有关。
Objective:To explore the effect and mechanism of Portulacae Herba protecting carbon tetrachloride(CCl4)-induced acute liver injury.Method:Sixty Kunming mice were randomly divided into normal group,model group,silybin group(200 mg·kg^-1)and Portulacae Herba high,medium,low(2,1,0.5 g·kg^-1)dose groups.After continuous intragastric administration for 5 days,mice in each group were intraperitoneally injected with 0.2%CCl4 peanut oil solution to establish acute liver injury model,except normal mice.After 23 hours of modeling,serum and liver tissue were collected.Fully automatic analysis of serum serum liver function indicators in mice.Liver tissues were taken for hematoxylin-eosin staining(HE)staining to observe liver pathological changes.RNA Sequencing(RNA-seq)was used to analyze differential genes and functional enrichment,real-time fluorescence quantification PCR(Real-time PCR)was used to verify the mRNA expression of cytochrome P450 family members(CYP)26A1,CYP2C37,CYP2C44,CYP2C50,CYP2C54.Result:Compared with normal group,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),total bilirubin(TBIL),malondialdehyde(MDA)in model group were significantly increased(P<0.05),and the activities of triglyceride(TG)and superoxide dismutase(SOD)were significantly decreased(P<0.05).Compared with model group,Portulaca Herba significantly reduced ALT,AST,TBIL and MDA levels in mice with acute liver injury(P<0.05),significantly increased SOD activity(P<0.01),and decreased the degree of liver tissue damage in mice.Compared with normal group,the mRNA expressions of CYP2C44,CYP2C50 in mice with acute liver injury were significantly decreased(P<0.05).Compared with model group,the mRNA expressions of CYP26A1,CYP2C37,CYP2C44,CYP2C50 and CYP2C54 were significantly increased in all dose groups of Portulaca Herba(P<0.05,P<0.01).Conclusion:Portulacae Herba has significant protective effects on acute liver injury caused by CCl4,and its mechanism may be related to the regulation of cytochrome P450 related genes.
作者
周璐
宋新龙
吕军苹
贺薏帆
庞宗然
鲁碧楠
ZHOU Lu;SONG Xin-long;LYU Jun-ping;HE Yi-fan;PANG Zong-ran;LU Bi-nan(School of Pharmacy,Minzu University of China,Beijing 100081,China;Key Laboratory of Ethnomedicine of Education Ministry,Minzu University of China,Beijing 100081,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第10期35-43,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
中央民族大学硕士研究生自主科研项目(SSZZKY-2019112)。
