选择性α_(1B)、α_(1D)肾上腺素受体亚型阻断剂对大鼠肝星状细胞的影响  

Effect of selective α_(1B)-and α_(1D)-adrenoceptors antagonists on the rat hepatic stellate cells

作　　者：刘婷婷[1,2] 丁体龙[2] 马勇[1,2] 魏伟[1] 

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,合肥230032 [2]解放军第123医院肝病中心,蚌埠233015

出　　处：《安徽医科大学学报》2013年第10期1191-1195,共5页Acta Universitatis Medicinalis Anhui

基　　金：2010年度军区医学科技创新经费资助项目(编号:10MA037)

摘　　要：目的探讨交感神经递质去甲肾上腺素(NA)和α1B、α1D肾上腺素受体(α1B-AR,α1D-AR)亚型阻断剂对大鼠肝星状细胞株(HSC-T6)激活、增殖和细胞外基质(ECM)分泌的影响。方法体外培养HSC-T6,分为以下9组:对照组,为单纯培养HSC-T6;NA(10-4、10-5、10-6、10-7、10-8、10-9mol/L)组;氯乙基可乐定(CEC)(10-5mol/L)组,为α1B-AR阻断剂;BMY7378(10-5mol/L)组,为α1D-AR阻断剂。MTT法测定细胞增殖;RT-PCR法测定HSC-T6活化指标:转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA);ECM分泌指标:金属蛋白酶组织抑制剂-1(TIMP-1)、I型胶原(ColⅠ)的表达。结果 NA对HSC-T6具有明显的促增殖作用,呈浓度依赖性,加入α1B-AR、α1D-AR阻断剂,细胞增殖均受到明显抑制。NA促进HSC-T6的TGF-β1、α-SMA、TIMP-1、ColⅠ表达;加入α1B-AR、α1D-AR阻断剂可显著抑制TGF-β1、α-SMA、TIMP-1、ColⅠ的表达。结论交感神经递质NA对HSC-T6的激活、增殖和ECM分泌有促进作用,可能通过α1B-AR、α1D-AR起作用。Objective To investigate the effect of noradrenaline （ NA ） as an agonist for adenoreceptor and a1D-adrenoceptors （a1B-, a1D-AR） antagonists （ Chloroethylclonidine dihydrochloride, BMY7378 ） as antagonists for adenoreceptors on the activation and proliferation of rat hepatic stellate cells （ HSC-T6 ） and on their synthesis capacity of extracellular matrix （ECM）. Methods Cultured HSC-T6 were divided into 9 groups： Control group, NA （10-4, 10-5, 10-6, 10-7, 10-8, 10-9mol/L） group, Chloroethylblonidine dihydrochloride （CEC） （a1B-AR antagonist） group, BMY7378 （a1D-AR antagonist） group. After NA and the antagonists of adrenoceptor subtypes were delivered to the DMEM containing cultured HSC-T6, MTT assay was used to evaluate the cell proliferation. Meanwhile, the expressions of transforming growth fact beta 1 （TGF-β1） and smooth muscle a-actin （ot-SMA） in HSC-T6 were detected by RT-PCR. The expressions of tissue inhibitor of metalloproteinase 1 （ TIMP-1 ） and collagen-I （Col I ） in HSC-T6 were detected by RT-PCR. Results NA significantly induced HSC-T6 proliferation in a concentration-dependent manner,which was reduced by the antagonists of a1B-AR and a1D-AR. NA induced the mRNA expressions of TGF-β1, tx-SMA, TIMP-1 and Col I , which were reduced by the antagonists of a1B-AR and a1D-AR. Conclusion NA can promote the activation, proliferation and secretion of ECM of HSC-T6, mainly through a1B-AR and a1D-AR.

关 键 词：肝星状细胞 去甲肾上腺素 α1B肾上腺素受体 α1D肾上腺素受体 肝纤维化 

分 类 号：R966[医药卫生—药理学] R575.2[医药卫生—药学]