血管内皮生长因子表达与丹参预防肝小静脉闭塞病机制的研究
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摘要
目的利用不同剂量丹参干预土三七诱导小鼠肝小静脉闭塞病(HVOD)模型,检测血管内皮生长因子(VEGF)表达,探讨丹参预防HVOD发生的作用机制。方法将100只小鼠随机分为4组,分别予磷酸缓冲液(PBS)、土三七、土三七+100 mg/kg丹参、土三七+200 mg/kg丹参灌胃,连续30 d后处死小鼠。通过修改后Deleve评分标准评价小鼠HVOD成模情况;免疫组化检测VEGF蛋白表达水平;RT-PCR检测VEGF mRNA水平。结果丹参干预组与土三七模型组比较,VEGF蛋白及mRNA表达水平显著降低(P<0.05),200 mg/kg丹参组的VEGF表达水平较100 mg/kg丹参组下降更明显(P<0.05)。结论不同剂量丹参可减少土三七诱导小鼠HVOD的发生,抑制VEGF的表达可能是丹参预防HVOD发生的重要作用机制之一。
Objective To investigate the mechanism of Salvia miltiorrhiza in preventing mice hepatic veno-occlusive disease(HVOD) induced by gynura segetum, VEGF expression was detected and different concentrations of Salvia miltiorrhiza was used to prevent the HVOD.Methods One hundred female Kunming mice were randomly classified into four groups. The control group was treated with PBS, model group was induced by gynura segetum, gynura segetum groups preventively treated with Salvia miltiorrhiza at two dosages(gynura segetum+Salvia miltiorrhiza,100 mg/kg, 200 mg/kg). The mice were sacrificed on the 30 st day. The modified Deleve scoring standard was used to evaluate the modeling of mice HVOD. The expression of VEGF was detected by immunohistochemistry and RT-PCR.Results Compared with gynura segetum group, the Salvia miltiorrhiza groups had significant decreased in the level of VEGF(P<0.05).Conclusion Salvia miltiorrhiza with different concentrations has therapeutic effect on HVOD induced by gynura segetum, and inhibition expression of VEGF may be one of the important mechanisms of Salvia miltiorrhiza in preventing HVOD.
Objective To investigate the mechanism of Salvia miltiorrhiza in preventing mice hepatic veno-occlusive disease(HVOD) induced by gynura segetum, VEGF expression was detected and different concentrations of Salvia miltiorrhiza was used to prevent the HVOD.Methods One hundred female Kunming mice were randomly classified into four groups. The control group was treated with PBS, model group was induced by gynura segetum, gynura segetum groups preventively treated with Salvia miltiorrhiza at two dosages(gynura segetum+Salvia miltiorrhiza,100 mg/kg, 200 mg/kg). The mice were sacrificed on the 30 st day. The modified Deleve scoring standard was used to evaluate the modeling of mice HVOD. The expression of VEGF was detected by immunohistochemistry and RT-PCR.Results Compared with gynura segetum group, the Salvia miltiorrhiza groups had significant decreased in the level of VEGF(P<0.05).Conclusion Salvia miltiorrhiza with different concentrations has therapeutic effect on HVOD induced by gynura segetum, and inhibition expression of VEGF may be one of the important mechanisms of Salvia miltiorrhiza in preventing HVOD.
引文
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[9] HELMY A.Review article:updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome [J].Aliment Pharmacol Ther,2006,23(1):11-25.DOI:10.1111/j.1365-2036.2006.02742.x.
[10] NAKAMURA K,HATANO E,NARITA M,et al.Sorafenib attenuates monocrotaline-induced sinusoidal obstruction syndrome in rats through suppression of JNK and MMP-9 [J].J Hepatol,2012,57(5):1037-1043.DOI:10.1016/j.jhep.2012.07.004.
[2] DELEVE L D,VALLA D C,GARCIA-TSAO G,et al.Vascular disorders of the liver [J].Hepatology,2009,49(5):1729-1764.DOI:10.1002/hep.22772.
[3] YANG L,ZHU H Y,CHEN Z,et al.Comparison of the hepatic veno-occlusive disease models induced by gynura segetum,monocrotaline and cyclophosphamide [J].Zhonghua Gan Zang Bing Za Zhi,2010,18(12):944-945.DOI:10.3760/cmaj.issn.1007-3418.2010.12.017.
[4] MCDONALD G B,SHARMA P,MATTHEWS D E,et al.Veno-occlusive disease of the liver after bone marrow transplantation:diagnosis,incidence,and predisposing factors [J].Hepatology,1984,4(1):116-122.
[5] JONES R J,LEE K S,BESCHOMER W E,et al.Venoocclusive disease of the liver following bone marrow transplantation [J].Transplantation,1987,44(6):778-783.
[6] KUMAR S,DELEVE L D,KAMATH P S,et al.Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation [J].Mayo Clin Proc,2003,78(5):589-598.DOI:10.4065/78.5.589.
[7] 杨丽,霍继荣,朱洪怡,等.丹参对土三七诱导小鼠肝小静脉闭塞病预防治疗效果的观察[J].肝脏,2013,18(2):105-107.DOI:10.3969/j.issn.1008-1704.2013.02.013.
[8] IGUCHI A,KOBAYASHI R,YOSHIDA M,et al.Vascular endothelial growth factor (VEGF) is one of the cytokines causative and predictive of hepatic veno-occlusive disease (VOD) in stem cell transplantation [J].Bone Marrow Transplant,2001,27(11):1173-1180.DOI:10.1038/sj.bmt.1703061.
[9] HELMY A.Review article:updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome [J].Aliment Pharmacol Ther,2006,23(1):11-25.DOI:10.1111/j.1365-2036.2006.02742.x.
[10] NAKAMURA K,HATANO E,NARITA M,et al.Sorafenib attenuates monocrotaline-induced sinusoidal obstruction syndrome in rats through suppression of JNK and MMP-9 [J].J Hepatol,2012,57(5):1037-1043.DOI:10.1016/j.jhep.2012.07.004.