糖基化终末产物对活化肝星状细胞合成前胶原及致纤维化细胞因子的影响

目的探讨不同浓度的糖基化终末产物（AGEs）对肝星状细胞（HSC）活性的影响。方法体外合成糖基化牛血清白蛋白（AGE-BSA）,以不同浓度的AGE-BSA刺激HSC,观察AGE受体（RAGE）、转化生长因子（TGFβ1）,结缔组织生长因子（CTGF）、Ⅰ、Ⅲ型前胶原mRNA;ELISA法检测细胞上清液TGFβ1及Ⅰ、Ⅲ型前胶原蛋白的水平。结果高浓度的AGE-BSA（100μg/ml）培养24 h便能促进RAGE、TGFβ1、CTGF和Ⅰ、Ⅲ型前胶原mRNA的表达,并随着时间延长而升高,细胞上清液蛋白水平有同样改变。结论一定浓度的AGEs能促进HSC前胶原及致纤维化细胞因子的表达,并呈时效性改变。AGEs对肝纤维化可能起到促进作用。

The effect of advanced glycation end products on biological activity of hepatic stellate cell

Objective To investigate the effect of advanced glycation end products on the biological activity of rat hepatic stellate cell（HSC）.Methods AGE-BSA was synthesized by incubating glucose with BSA in vitro.HSC-T6 was incubated with different concentrations of AGE-BSA.Messenger RNA type I and type Ⅲ precollagen,receptor of AGEs（RAGE）,TGF β1 and CTGF were determined by real-time PCR.Cell supernatant Type I and type Ⅲ precolagen,and TGF β1 were determined by ELISA.Results The expressions of mRNA type I and type Ⅲ precollagen,RAGE,TGF β1 and CTGF were increased after incubated with 100μg/ml AGE-BSA for 24 hours.The expression of mRNA level in cell supernatant increased with prolonged incubation time.Conclusion Glycation end products induce a time-dependant expression of precollagen and fibrogenic cytokines.Glycation end products may have a role in the development of liver fibrosis.