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1.中央民族大学 药学院,北京 100081
2.中央民族大学 民族医药教育部重点实验室,北京 100081
3.天津中医药大学,天津 301617
[第一作者] 周璐,在读硕士,从事民族医药防治肝损伤研究,E-mail:zhoulu5661@163.com
*鲁碧楠,博士,助理研究员,从事民族医药防治肝损伤研究,E-mail:binanlu@muc.edu.cn
收稿日期:2019-12-07,
网络出版日期:2020-02-06,
纸质出版日期:2020-05-20
移动端阅览
周璐, 宋新龙, 吕军苹, 等. 马齿苋对四氯化碳诱导小鼠急性肝损伤的保护作用[J]. 中国实验方剂学杂志, 2020,26(10):35-43.
Lu ZHOU, Xin-long SONG, Jun-ping LYU, et al. Hepatoprotective Effect of Portulacae Herba on Carbon Tetrachloride Induced Acute Liver Injury in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(10): 35-43.
周璐, 宋新龙, 吕军苹, 等. 马齿苋对四氯化碳诱导小鼠急性肝损伤的保护作用[J]. 中国实验方剂学杂志, 2020,26(10):35-43. DOI: 10.13422/j.cnki.syfjx.20201036.
Lu ZHOU, Xin-long SONG, Jun-ping LYU, et al. Hepatoprotective Effect of Portulacae Herba on Carbon Tetrachloride Induced Acute Liver Injury in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(10): 35-43. DOI: 10.13422/j.cnki.syfjx.20201036.
目的:
2
探讨马齿苋保护四氯化碳(CCl
4
)所致急性肝损伤的作用及机制。
方法:
2
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% CCl
4
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:
2
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:
2
马齿苋对CCl
4
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:
2
To explore the effect and mechanism of Portulacae Herba protecting carbon tetrachloride (CCl
4
)-induced acute liver injury.
Method:
2
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% CCl
4
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:
2
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:
2
Portulacae Herba has significant protective effects on acute liver injury caused by CCl
4
and its mechanism may be related to the regulation of cytochrome P450 related genes.
J LUAN , D JU . Inflammasome: a double-edged sword in liver diseases [J]. Front Immunol , 2018 , 9 : 2201 .
H MALHI , M E GUICCIARDI , G J GORES . Hepatocyte death: a clear and present danger [J]. Physiol Rev , 2010 , 90 ( 3 ): 1165 - 1194 .
吴艳玲 , 廉丽花 , 南极星 . 中药有效成分治疗肝损伤及肝纤维化作用机制的研究进展 [J]. 世界华人消化杂志 , 2016 , 24 ( 30 ): 4144 - 4150 .
黄鹏 , 李家焕 , 邱华 , 等 . 肝损伤中医药治疗研究概况 [J]. 世界最新医学信息文摘 , 2019 , 19 ( 66 ): 111 - 113 .
汪青楠 , 吕文良 , 倪瑶 , 等 . 中医治疗药物性肝损伤的研究进展 [J]. 中医药导报 , 2019 , 25 ( 14 ): 125 - 128 .
A M AMIRUL , A S JURAIMI , M Y RAFII , et al . Genetic improvement of purslane ( Portulaca oleracea L.) and its future prospects [J]. Mol Biol Rep , 2014 , 41 ( 11 ): 7395 - 7411 .
国家药典委员会 . 中华人民共和国药典:一部 [M]. 北京 : 中国医药科技出版社 , 2015 : 49 .
陈维维 , 张小莉 , 桑晓林 . 马齿苋保肝作用的研究进展 [J]. 中医临床研究 , 2017 , 9 ( 35 ): 142 - 144 .
S HONGGUANG , L XUEFENG , T GUSHENG , et al . Ethanol extract of Portulaca oleracea L.reduced the carbon tetrachloride induced liver injury in mice involving enhancement of NF- κ B activity [J]. Am J Transl Res , 2014 , 6 ( 6 ): 746 - 755 .
X F LIU , C G ZHENG , H G SHI , et al . Ethanol extract from Portulaca oleracea L.attenuated acetaminophen-induced mice liver injury [J]. Am J Transl Res , 2015 , 7 ( 2 ): 309 - 318 .
A EIDI , MORTAZAVI , J Z MOGHADAM , et al . Hepatoprotective effects of Portulaca oleracea extract against CCl 4 -induced damage in rats [J]. Pharm Biol , 2014 , 53 ( 7 ): 1 - 10 .
徐淑云 , 卞如廉 , 陈修 . 药理实验方法学 [M]. 3版 . 北京 : 人民卫生出版社 , 2001 : 1346 .
L ZHAO , Y JIN , K DONAHUE , et al . Tissue repair in the mouse liver following acute carbon tetrachloride depends on injury-induced Wnt/ β -catenin signaling [J]. Hepatology , 2019 , 69 ( 6 ): 2623 - 2635 .
P HE , B ZENG , X L ZHANG , et al . Protective effect of apoptosis signal-regulating kinase 1 inhibitor against mice liver injury [J]. Asian Pac J Trop Med , 2016 , 9 ( 3 ): 283 - 287 .
B Y YANG , X Y ZHANG , S W GUAN , et al . Protective effect of Procyanidin B 2 against CCl 4 -induced acute liver injury in mice [J]. Molecules , 2015 , 20 ( 7 ): 12250 - 12265 .
B G BRUINSMA , W WU , S ZAER , et al . Warm ischemic injury is reflected in the release of injury markers during cold preservation of the human liver [J]. PLoS One , 2015 , 10 ( 3 ): 1 - 9 .
S B GUO , Q LI , Z J DUAN , et al . Octreotide attenuates liver fibrosis by inhibiting hepatic heme oxygenase-1 expression [J]. Mol Med Rep , 2015 , 11 ( 1 ): 83 - 90 .
I G PECHENKINA , S V KOZIN , D V BULANOV . Immunohistochemical assay of murine liver tissue using monoclonal antibodies to NO-synthase 2 and TNF- α under tetrachloromethane toxic injury conditions [J]. Eksp Klin Farmakol , 2015 , 78 ( 2 ): 20 - 23 .
J LYKKESFELDT . Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking [J]. Clin Chim Acta , 2007 , 380 ( 1/2 ): 50 - 58 .
S W ROCHA , M E DE FRANCA , G B RODRIGUES , et al . Diethylcarbamazine reduces chronic inflammation and fibrosis in carbon tetrachloride-induced liver injury in mice [J]. Mediators Inflamm , 2014 , doi: 10.1155/2014/696383 http://dx.doi.org/10.1155/2014/696383 .
H JIANG , W H WONG . Statistical inferences for isoform expression in RNA-Seq [J]. Bioinformatics , 2009 , 25 ( 8 ): 1026 - 1032 .
T NIWA , N MURAYAMA , H YAMAZAKI . Oxidation of endobiotics mediated by xenobiotic-metabolizing forms of human cytochrome P450 [J]. Curr Drug Metab , 2009 , 10 ( 7 ): 700 - 712 .
H WANG , Y ZHAO , J A BRADBURY , et al . Cloning,expression,and characterization of three new mouse cytochrome P450 enzymes and partial characterization of their fatty acid oxidation activities [J]. Mol Pharmacol , 2004 , 65 ( 5 ): 1148 - 1158 .
W WANG , J YANG , W QI , et al . Lipidomic profiling of high-fat diet-induced obesity in mice:importance of cytochrome P450-derived fatty acid epoxides [J]. Obesity , 2017 , 25 ( 1 ): 132 - 140 .
H SUN , X Y LOU , X Y WU , et al . Up-regulation of CYP2C19 expression by BuChang NaoXinTong via PXR activation in HepG2 cells [J]. PLoS One , 2016 , 11 ( 7 ): e0160285 .
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