5-羟色胺受体在肝星状细胞上的表达及5-羟色胺对肝星状细胞生物学活性的影响  

Expression of 5-hydroxytamine receptors in hepatic stellate cell and action of 5-hydroxytamine on biological characteristics of hepatic stellate cell

作　　者：李涛[1] 冷希圣[1] 翁山耕[1] 彭吉润[1] 魏玉华[1] 牟东成[1] 王万祥[1] 朱继业[1] 

机构地区：[1]北京大学人民医院肝胆外科,100044

出　　处：《中华外科杂志》2003年第3期175-179,共5页Chinese Journal of Surgery

基　　金：国家自然科学基金资助项目 ( 39970 72 2 )

摘　　要：目的　探讨 5 羟色胺 ( 5 HT)受体在肝星状细胞 (HSC)的表达及 5 HT通过其受体的介导对HSC生物学活性的影响。　方法　采用肝脏离体胶原酶灌注消化及密度梯度离心的方法来分离培养HSC ;RT PCR方法检测HSC中 5 HT受体 1B、2A、2B、3等亚型的表达 ;Westernblot方法检测 5 HT及其 2A受体阻断剂酮色林、3型受体阻断剂恩丹西隆对HSC表达TGF β1和Smad4的影响。建立聚硅酮膜培养法 ,将HSC培养在聚硅酮膜上 ,研究 5 HT及酮色林、恩丹西隆对HSC收缩的影响。结果　HSC表达 5 HT的 1B、2A、2B等受体亚型 ,不表达 3亚型。5 HT明显促进HSC表达TGF β1和Smad4(P <0 0 5 ) ,酮色林能抑制TGF β1和Smad4的表达。恩丹西隆的作用不明显。 5 HT能促进HSC的收缩 ,并成量效依赖关系 ,这种收缩作用能被酮色林所阻断 ,不被恩丹西隆阻断。　结论　HSC表达 5 HT的多种受体亚型 ,5 HT通过其受体的介导对HSC的生物学活性发生影响 ,在肝硬化、门静脉高压症的发生发展中起了一定的作用。Objective To investigate the expression of 5-hydroxytamine receptors in hepatic stellate cells HSCs and action of 5-hydroxytamine on biological characteristics of HSC. Methods Liver ex vivo perfusion of collagenase and density gradient centrifugation were used to isolate hepatic stellate cell. RT-PCR was used to detect the expression of 5-hydroxytamine receptor subtypes 1A, 2A, 2B and 3. Western blot hybridization was used to elucidate the effect of 5-hydroxytamine and its 2A receptor antagonist ketanserin and 3 receptor antagonist ondanosetron on expression of transforming growth factor-β1 (TGF-β1) and Smad4 in HSC. HSCs were cultured on silicone membrane. The effect of 5-hydroxytamine, ketanserin and ondanosetron on cell contraction were studied. Results HSC expressed 5-hydroxytamine receptors subtypes 1A, 2A and 2B. 5-hydroxytamine significantly increased the expression of TGF-β1 and Smad4 in HSC ( P<0.05). This was antagonized by ketanserin, not by ondanosetron. 5-hydroxytamine induced cell contraction in a dose-dependant manner. Ketanserin antagonized this action, but ondanosetron did not. Conclusions HSCs express 5-hydroxytamine receptors. 5-hydroxytamine could affect the biological characteristics of HSC through its receptor mediation, and may play a role in the pathogenesis of liver cirrhosis and portal hypertension.

关 键 词：5-羟色胺受体 肝星状细胞 5-羟色胺 生物学活性 转化生长因子 肝硬化 门静脉高压症 

分 类 号：R657.3[医药卫生—外科学]