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中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (11): 1229-1233.

• 基础研究 • 上一篇    下一篇

Caspase抑制剂F1013对急性肝衰竭大鼠肝细胞凋亡的影响

邓利娟1, 李湛军1, 罗楹2, 范慧红1   

  1. 1中国药品生物制品检定所,北京100050;
    2上海睿星基因技术有限公司,上海 201203
  • 收稿日期:2010-10-08 修回日期:2010-11-20 出版日期:2010-11-26 发布日期:2020-09-16
  • 作者简介:邓利娟,女,硕士,副研究员,主要从事生化药理与生物检定工作。Tel: 010-67095464 E-mail: lisadeng06@yahoo.com.cn

Effect of the caspase selective inhibitor F1013 on hepatocyte apoptosis in rats with fulminant hepatic failure

DENG Li-juan1, LI Zhan-jun1, LUO Ying2, FAN Hui-hong1   

  1. 1National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050,China;
    2Shanghai Genomics Inc.,Shanghai 201203,China
  • Received:2010-10-08 Revised:2010-11-20 Online:2010-11-26 Published:2020-09-16

摘要: 目的: 观察F1013对D-氨基半乳糖(D-GalN)及脂多糖(LPS)所致大鼠急性肝衰竭模型的保护作用,并对其机制进行初步探讨。方法: 采用D-GalN/LPS诱导大鼠急性肝衰竭模型,用全自动生化分析仪检测血清ALT、AST和总胆红素(TBIL)含量;用苏木素-伊红(HE)染色,观察肝组织病理学变化;采用流式细胞学技术和原位末端标记(TUNEL)法检测肝细胞凋亡情况。结果: 模型组大鼠血清ALT、AST、TBIL水平和肝细胞凋亡率较正常对照组均显著升高(P<0.01)。F1013(5,2.5,1.25 mg/kg) 给药组大鼠肝组织病理损伤程度明显轻于模型组;血清ALT、AST水平和肝细胞凋亡率均较模型组明显降低(P<0.01 或P<0.05),另F1013(5 mg/kg)给药组血清TBIL水平较模型组明显降低(P<0.01)。结论: F1013对GalN/LPS引起的大鼠急性肝衰竭有较好的保护作用,其机制可能与抑制肝细胞凋亡有关。

关键词: F1013 , 急性肝衰竭, 凋亡

Abstract: AIM: To observe the protective effect of F1013 on fulminant hepatic failure (FHF) induced by lipopolysaccharide(LPS) plus D-galactosamine (D-GalN) in rats and to investigate its mechanism of action. METHODS: The rat model of FHF was induced by intra-peritoneal injection of LPS plus D-GalN. The contents of ALT, AST and total bilirubin (TBIL) were examined by an entire automatic biochemistry, the hepatic pathological changes were observed with hematoxylin-eosin(HE) stain , and the hepatocyte apoptosis was detected with FCM and TUNEL. RESULTS: Compared with the control group,serum levels of ALT,AST and TBIL and the expression of hepatocyte apoptosis in rats of the model group were significantly elevated (P<0.01).Compared with the model group,5,2.5,1.25 mg/kg F1013 treatment groups could effectively improve the hepatic tissue injury, reduce serum levels of ALT and AST and the expression of hepatocyte apoptosis (P<0.01 or P<0.05) , 5 mg/kg F1013 treatment group reduce serum levels of TBIL(P<0.01). CONCLUSION: It is shown that F1013 has a promising protective effect on rats with FHF caused by LPS plus D-GaIN, and its mechanism is probably related to the inhibition of liver tissue cell apoptosis.

Key words: F1013 , Fulminant hepatic failure , Apoptosis

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