吉林大学学报(医学版)

• 基础研究 • 上一篇    下一篇

雷帕霉素对四氯化碳油致肝纤维化模型大鼠的治疗作用

钟志宏1,颜文贞2,戴 东1,陈土明1,胡祖超1   

  1. 1.广东医学院附属医院肝胆外科,广东 湛江 524001;2.广东医学院护理学院,广东 湛江 524023
  • 收稿日期:2013-06-20 发布日期:2013-12-12
  • 通讯作者: 戴 东(Tel:0759-2387417,E-mail: daidong2008@126.com; 颜文贞(Tel:0769-22896280,E-mail:39367849@qq.com) E-mail:daidong2008@126.com;39367849@qq.com
  • 作者简介:钟志宏(1984-),男,广东省深圳市人,医师,医学硕士,主要从事肝胆 外科方面的研究。
  • 基金资助:

     广东省湛江市2012年度财政资金科技专项竞争性项目资助课题 (湛科2012C0302)

Therapeutic effect of rapamycin on  liver fibrosis model
rats induced by carbon tetrachloride  oil  


ZHONG  Zhi-hong1,YAN  Wen-zhen2,DAI  Dong1,CHEN Tu-ming1,HU Zu-chao1   

  1. 1.Department of Hepatobiliary Surgery,Affilicted Hospital,Guangdong Medical College,Zhanjiang  524001,China;2.College of Nursing,Guangdong Me
    dical College,Zhanjang 524023,China
  • Received:2013-06-20 Published:2013-12-12

摘要:

目的:探讨雷帕霉素(RAPA)和脾切除对肝纤维化大鼠肝和脾组织中转化生长因子β1(TGF-β1)表达水平及肝和脾组织病理形态学的影响,阐述其治疗肝纤维化的作用。方法:30只大鼠随机分成正常对照组、肝纤维化模型组、RAPA组、脾切除组和联合治疗组,每组6只。以四氯化碳(CCl4)花生油诱导建立大鼠肝纤维化模型。光镜
下观察各组大鼠肝和脾组织病理形态学改变;检测TGF-β1在肝和脾组织中的表达水平;动态监测大鼠肝纤维化进程中血清TGF
-β1水平的变化。结果:形态学表现为肝纤维化模型组大鼠肝组织呈混合滴性脂肪变,炎症细胞侵润,小胆管增
生,纤维间隔增生穿插包绕肝细胞;RAPA组、脾切除组和联合治疗组大鼠肝组织形态呈不同程度的改善,尤以联合治疗组明显。与肝纤维化模型组比较,脾切
除组、联合治疗组和RAPA组大鼠肝组织中TGF-β1表达水平降低(P<0.05或P<0.01),与肝纤维化模型组比较,RAPA组大鼠脾组织TGF-β1表达水平降低显著(
P<0.01)。与正常对照组比较,肝纤维化模型组和RAPA组大鼠脾组织中TGF-β1表达水平升高(P<0.01);第8周时,与肝纤维化模型组比较,RAPA组、脾切除组和联合治疗组大鼠血清TGF-β1水平降低(P<0.05或P<0.01)。联合治疗组大鼠血清TGF-β1表达水平较脾切除组降低明显(P<0.05),但与RAPA
组比较差异无统计学意义(P>0.05)。结论:RAPA和脾切除能显著下调大鼠肝和脾组织中TGF-β1表
达水
平及血清TGF-β1表达水平,减轻肝组织形态学改变程度,缓解大鼠肝脏纤维变性的进程。

关键词: 肝纤维化,  , 雷帕霉素,  , 脾切除,  , 转化生长因子&beta, 1

Abstract:

Objective To  study the effects of rapamycin(RAPA) and splenectomy on
 the  expression levels of transforming growth factor-β(TGF-β1) in liver and
 spleen tissues of rats  with liver fibrosis and the pathological morphology of
 
  liver and spleen tissues,and to disscuss  its role in the treatment of
 liver fibrosis.Methods  30 rats were randomly divided into normal control group,

RAPA group,liver  fibrosis model group,splenectomy group, and combination treatment
 group; there were 6 rats in  each group.Carbon tetrachloride (CCl4) peanut oil was used to 

establish the  liver fibrosis  rat  models.The  morphological changes of liver and spleen tissues of the  rats in various  grou
ps were observed under light microscope;the  expression levels of TGF-β1  in liver  and spleen tissues and the expressi
on level of  serm TGF-β1 were detected.Results The morphology  results showed that the 
 rats in  liver fibrosis model group presented  mixing drops of fatty degenerati
on,and the inflammatory cells invasion,and small bile duct hyperplasia,and there
 were hyperplasia of fibrous septum wrapping liver cells; the pathomorphological changes of the
 
 rats in RAPA  group,splenectomy  group and combination treatment  group  were  improved with different
 degrees,especially  in combination treatment group.Compared with  liver fibrosis model  group,the expression levels of TGF-β1 of the rats in

splenectomy group,combination  treeatment  group, and RAPA group were decreased (P<0.05 or P<0.01).Compared with liver fibrosis model group,the

expression level of  TGF-β1 in spleen tissue of the rats in  RAPA group was decreased(P<0.01).Compared with normal control group,the expression levels of TGF-β1 in spleen tissue of the rats in liver fibrosis group and RAPA group were increased(P<0.01).At the 8th week,compared with  liver fibrosis model group,the expression lev
els of serum TGF-β1 of the rats in RAPA group,splenectomy group, and combination treatment group were decreased(P<0.05 or P<0.01).Compared with splen
ectomy group,the expression level of serum TGF-β1 of the rats in combination treatment group was decreased(P<0.05),


but there was no significant difference of the expression levels of serum TGF-β1 between combination treatment
 group and RAPA group(P>0.05).Conclusion RAPA and splenectomy can significantly lower the
 expression level of serum  TGF-β 1 and  the expression level of TGF-β1 in liver  and spleen tissues of the rats
 and reduce the morphological changes in the liver tissue and  ease the process of liver fibrosis  in rats.

Key words: liver fibrosis, rapamycin, splenectomy, transforming growth factor-beta 1

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