栀子油对ConA诱导的小鼠急性免疫性肝损伤的保护作用
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摘要
研究栀子油对刀豆蛋白A(ConA)诱导的小鼠免疫性肝损伤的保护作用,并探讨其作用机制。将小鼠随机分成空白组、模型组、联苯双酯组,栀子油低、中、高剂量组,各给药组每天给药1次,连续给药10 d,末次给药1 h后,除空白组外,其他各组尾静脉注射ConA(15 mg/kg),制备小鼠急性免疫性肝损伤模型。测定小鼠血清中ALT、AST和LDH的含量及肝脏组织匀浆中SOD活性和NO、MDA的含量,RT-PCR检测肝组织中TNF-α、CXCL-10 mRNA和IFN-γmRNA的表达量,HE染色观察肝组织的病理学变化。结果表明:与模型组相比,栀子油各剂量组均能降低血清ALT、AST和LDH的含量,提高SOD活性,降低肝组织NO、MDA的产生,下调TNF-α、CXCL-10mRNA和IFN-γmRNA的相对表达量,肝组织变性及坏死等病理症状明显改善,尤以栀子油高剂量组效果最佳。栀子油对ConA诱导小鼠免疫性肝损伤有明显的保护作用,其保肝的机制可能与提高抗氧化酶体系活力,抑制氧化应激反应及炎性因子表达有关。
The protective effect of Gardenia oil on acute immunologic liver injury induced by concanavalin A( ConA) in mice was investigated and the action mechanism was discussed. Mice were randomly divided into blank,model,biphenyl dimethylester,Gardenia oil low,middle and high dose groups. The medicine was performed once daily for 10 d,then the model of immunologic liver injury was prepared by intravenous injection of ConA( 15 mg/kg) in the tail of mice in each group except for blank group one hour after the last treatment. The contents of ALT,AST and LDH in the blood serum,the activity of SOD and the levels of MDA and NO in the liver organs of mice were determined,the expressions of TNF-αmRNA,CXCL-10 mRNA and IFN-γ mRNA expressions in liver tissue were detected by RT-PCR,and pathological morphological changes in liver tissue were monitored by HE dyeing. The results showed that compared with model group,each dose group of Gardenia oil could reduce the contents of serum ALT,AST and LDH, improve the activity of SOD,reduce the productions of NO and MDA in liver tissue,and decrease the relative expressions of TNF-α mRNA,CXCL-10 mRNA and IFN-γmRNA in liver tissue,also pathological damage in liver was relieved,meanwhile the effect of the high dose group of Gardenia oil was the best.Gardenia oil had markedly protective effect on immunologic injury induced by ConA in mice,and the mechanism might be depended on elevating antioxidant enzymes activity,inhibiting oxidative stress and inflammation factors expression.
The protective effect of Gardenia oil on acute immunologic liver injury induced by concanavalin A( ConA) in mice was investigated and the action mechanism was discussed. Mice were randomly divided into blank,model,biphenyl dimethylester,Gardenia oil low,middle and high dose groups. The medicine was performed once daily for 10 d,then the model of immunologic liver injury was prepared by intravenous injection of ConA( 15 mg/kg) in the tail of mice in each group except for blank group one hour after the last treatment. The contents of ALT,AST and LDH in the blood serum,the activity of SOD and the levels of MDA and NO in the liver organs of mice were determined,the expressions of TNF-αmRNA,CXCL-10 mRNA and IFN-γ mRNA expressions in liver tissue were detected by RT-PCR,and pathological morphological changes in liver tissue were monitored by HE dyeing. The results showed that compared with model group,each dose group of Gardenia oil could reduce the contents of serum ALT,AST and LDH, improve the activity of SOD,reduce the productions of NO and MDA in liver tissue,and decrease the relative expressions of TNF-α mRNA,CXCL-10 mRNA and IFN-γmRNA in liver tissue,also pathological damage in liver was relieved,meanwhile the effect of the high dose group of Gardenia oil was the best.Gardenia oil had markedly protective effect on immunologic injury induced by ConA in mice,and the mechanism might be depended on elevating antioxidant enzymes activity,inhibiting oxidative stress and inflammation factors expression.
引文
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[15]莫凤珍,孔晓龙.软坚护肝片对刀豆蛋白A所致小鼠免疫性肝损伤的保护作用[J].广西医学,2015(6):752-754.
[16]DAI T,WU Y,LENG A S,et al.RXRα-regulated liver SAMe and GSH levels influence susceptibility to alcoholinduced hepatotoxicity[J].Experim Mol Pathol,2003,75(3):194-200.
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[3]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,2015:248.
[4]孟祥乐,李红伟,李颜,等.栀子化学成分及其药理作用研究进展[J].中国新药杂志,2011,20(11):959-967.
[5]邵坚,罗光明,朱继孝,等.栀子炮制前后7种成分的比较研究[J].中草药,2015,46(11):1629-1633.
[6]张风波,罗光明,肖日传,等.栀子油对四氯化碳所致小鼠急性肝损伤的保护作用[J].中国油脂,2017,42(7):128-131.
[7]TIEGS G,HENTSCHEL J,WENDEL A.A T cell-dependent experimental liver injury in mice inducible by concanavalin A[J].J Clin Investig,1992,90(1):196-203.
[8]JUNG K,KANG M,PARK C,et al.Protective role of V-set and immunoglobulin domain-containing 4 expressed on kupffer cells during immune-mediated liver injury by inducing tolerance of liver T-and natural killer T-cells[J].Hepatology,2012,56(5):1838-1848.
[9]WANG H X,LIU M,WENG S Y,et al.Immune mechanisms of Concanavalin A model of autoimmune hepatitis[J].World J Gastroenterol,2012,18(2):119-125.
[10]HEGDE V L,HEGDE S,CRAVATT B F,et al.Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids:involvement of regulatory Tcells[J].Mol Pharmacol,2008,74(1):20-33.
[11]FUJII Y.Management of postoperative nausea and vomiting in women scheduled for breast cancer surgery[J].JAnesth,2011,25(6):917-922.
[12]ANTONELLI A,FERRARI S M,GIUGGIOLI D,et al.Chemokine(C-X-C motif)ligand(CXCL)10 in autoimmune diseases[J].Autoimmun Rev,2014,13(3):272-280.
[13]秦佩,雷志明,吴双,等.槲皮素对Con A诱导自身免疫性肝损伤作用[J].中国公共卫生,2015,31(6):757-759.
[14]陈璐,张梅,姚红娥,等.波棱瓜子脂肪油对小鼠免疫性肝损伤的保护作用[J].华西药学杂志,2014,29(2):143-145.
[15]莫凤珍,孔晓龙.软坚护肝片对刀豆蛋白A所致小鼠免疫性肝损伤的保护作用[J].广西医学,2015(6):752-754.
[16]DAI T,WU Y,LENG A S,et al.RXRα-regulated liver SAMe and GSH levels influence susceptibility to alcoholinduced hepatotoxicity[J].Experim Mol Pathol,2003,75(3):194-200.