摘要
目的研究重组人角质细胞生长因子(K102)在体内和体外的生物活性。方法运用3T3BALB/c细胞和大鼠CCl4肝纤维化模型对K102在体内体外的生物活性进行测定。结果体外生物活性检测:K102明显抑制成纤维细胞的生长,bFGF对K102有一定拮抗作用,且具有剂量依赖性;体内生物活性检测:治疗给药组血清ALT,AST和肝组织羟脯氨酸含量较CCl4模型组明显改善。病理组织学检查见K102大、小剂量组肝细胞脂肪变性和水样变性比较轻,汇管区纤维组织仅有轻微增生。结论K102的抗肝纤维化作用可能是通过促进肝细胞增生、合成代谢,以及抑制成纤维细胞生长、减少纤维组织增生而产生的。
Abstract
OBJECTIVE To study the bioactivities of K102 in vivo and in vitro.METHODS The 3T3 BALB/c cell line and the rat model with liver fibrosis were Utilized to evaluate the bioactivities of K102 in vivo and in vitro. RESULTS The proliferation of fibroblasts was inhibited by K102 in vitro. A dose-dependent antagonistic effect was found between K102 and bFGF. The serum levels of ALT, AST and the liver hydroxyproline level in the treated groups were lower than that in the CCl4 model group. Pathological examination showed a slight fatty degeneration and hydropic degeneration was observed in the group treated with the high dose K102, the low dose K102, and the control group. And the fibroustissue hyperplasia of the portal area in the first two groups was more slight than that in the control group. CONCLUSION In vivo, K102 may play an important role in anti-fibrosis by promoting the proliferation and anabolism of hepatocytes, inhibiting the proliferation of liver fibroblasts and hyperplasia of fibroustissue.
关键词
角质细胞生长因子 /
生物活性 /
成纤维细胞
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Key words
keratinocyte growth factor /
bioactivities /
fibroblast /
liver fibrosis
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霍黉琦;李新平;范开;曹志飞;路冠南;汪成富.
重组人角质细胞生长因子的体内外作用研究[J]. 中国药学杂志, 2005, 39(22): 1749-1751
HUO Hong-qi;LI Xin-ping;FN Ki;CO Zhi-fei;LU Gun-nn;WNG Cheng-fu.
Functional evaluation of recombinant human kerotinocyte growth factor in vivo and in vitro[J]. Chinese Pharmaceutical Journal, 2005, 39(22): 1749-1751
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参考文献
[1］重庆富进生物医药有限公司. 新型人角质细胞生长因子突变体[P］. 中国. 发明专利. 03101156.X，2003-01-13
[2］王慧芳， 曾林. 肝纤维化动物模型研究进展[J］. 实用医药杂志， 2002， 19 (6)： 475.
[3］刘平， 高云华. 肝纤维化动物模型的建立[J］. 世界华人消化杂志， 2002， 10 (6)： 673.
[4］杨吉成，宋礼华，周建华，等.医用细胞工程[M］. 上海：上海交通大学出版社， 2001：92～93.
[5］玉涛， 魏红山， 王志荣，等.大黄素抗肝纤维化作用的实验研究[J］.中国肝脏病杂志， 2001， 9 (3)： 235.
[6］文才， 张锦生， 李华，等. 肝组织羟脯氨酸含量测定方法的优化[J］. 上海医科大学学报， 2000， 27 (4)： 295.
[7］Roint RS， Dafna BB， Ester S，et al. Differential effect of cell-associated heparan sulfates on the binding of keratinocyte growth factor (KGF) and acidic fibroblast growth factor to the KGF receptor [J］.J Biol Chem，1994，269(51)：32279.
[8］Hously RM， Charles F， Boyle W. Keratinocyte growth factor induces proliferation of hepatocytes and epithelial cells throughout the rat gastrointestinal tract [J］.J Clin Invest，1994，94 (5)：1764.
[9］Lawrence SP， Philip HK， Thomas OM，et al. KGF alters gene expression in human airway epithelia： potential regulation of the inflammatory response [J］.Physiol Genomics，2001，6：81.
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脚注
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基金
江苏省资源生物技术重点实验室开发基金(RBT20040504)
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