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肝素和α-干扰素抗肝纤维化的实验研究

Effects of heparin and alpha-interferon on liver fibrosis in rats

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【作者】 石军郝菁华任万华朱菊人孔祥辉

【Author】 SHI Jun,HAO Qing-hua,REN Wan-hua,ZHU Ju-ren,KONG Xiang-hui(Shandong Provincial Hospital,Jinan 250021,P.R.China)

【机构】 山东省立医院山东省立医院 山东济南250021山东济南250021

【摘要】 目的探讨肝素和α-干扰素抗肝纤维化的效果。方法将60只大鼠随机分为六组各10只,对照组(N组)皮下注射生理盐水;肝纤维化组(F组)皮下注射40%CCl4花生油溶液;肝素1组和肝素2组均皮下注射40%CCl4花生油溶液,21 d后分别予0.83 mg/(kg.d)、0.42 mg/(kg.d)肝素同时注射;干扰素1组和干扰素2组均皮下注射40%CCl4花生油溶液,21 d后分别予α-干扰素8.3万U/(kg.d)、5万U/(kg.d)同时注射。连续用药8周后处死各组大鼠,留取血清检测透明质酸(HA)、PC、层黏蛋白(LN)、型胶原(-C)水平;留取肝组织进行组织学观察。结果与F组比较,肝素1组和2组各项血清学指标均显著下降,干扰素1组和2组HA和PC水平显著下降;肝素1组和2组肝组织TGF-β1和PC-表达低于干扰素1组和2组。结论肝素、α-干扰素均有抗肝纤维化作用,前者效果较好。

【Abstract】 [Objective]To evaluate the effects of heparin and interferon-alpha on liver fibrosis.[Methods] 60 rats were randomly divided into 6 groups:rats in control group(N group) were injected subcutaneously with saline solution;in liver fibrosis group(F group)were injected subcutaneously with carbon tetrachloride;in heparin group 1 and 2 were first given carbon tetrachloride,then heparin after 21 days at 0.83 mg/(kg·d),0.42 mg/(kg·d);in interferon group 1 and 2 were given carbon tetrachloride,then interferon-alpha after 21 days at 83 000 U/(kg·d),50 000 U/(kg·d),respectively.All of the rats were killed after eight weeks and the serum levels of hyaluronate,collagen type Ⅳ,laminin,precollagen type Ⅲ and TGF-β1,were determined.Liver tissues were stained with HE and Masson trichrome staining.The expressions of precollagen type Ⅲ and TGF-β1 in liver tissues were measured with immunohistochemistry.[Results] The serum indexes of heparin treatment groups were significantly decreased compared with F group.The serum hyaluronate and precollagen type Ⅲ concentrations in interferon-alpha treatment groups were decreased significantly compared with F group.TGF-β1 PC-Ⅲ in heparin groups were lower than those in interferongroups.The results of collagen staining and immunohistochemistry showed that heparin could significantly inhibit the development of liver fibrosis.[Conclusions] Both heparin and interferon-alpha have antifibrosis effects.The effect of heparin is better than that of interferon-alpha.

【关键词】 肝脏纤维化肝素α-干扰素
【Key words】 liverfibrosisheparininterferon-alpha
【基金】 山东省卫生厅课题资助项目(2001,CA2CKA2号)
  • 【文献出处】 山东医药 ,Shandong Medical Journal , 编辑部邮箱 ,2007年11期
  • 【分类号】R575.2
  • 【下载频次】72
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