摘要
目的:研究25-羟维生素D3-1α-羟化酶(1α-羟化酶)质粒转染对角质形成细胞增殖、分化和凋亡的影响。方法:体外培养小鼠角质形成细胞(KC)转染1α-羟化酶后,观察细胞在形态上的变化对分化进行研究;利用Giemsa染色法和Tunel荧光素原位末端标记法对凋亡诱导作用进行观察。利用小鼠阴道上皮有丝分裂模型和小鼠尾部鳞片表皮模型对1α-羟化酶质粒转染对KC增殖和分化的影响进行研究。结果:携带1α-羟化酶的质粒转染KC可以非常显著的促进其分化,剂量与效应呈正相关;10-6mol/L的维生素D3和0.015μg/μL1α羟化酶质粒转染联合应用即可诱导KC细胞凋亡。1α-羟化酶质粒转染可以非常显著的抑制小鼠阴道上皮有丝分裂(P<0.01),显著促进小鼠尾部鳞片表皮模型中颗粒层的形成(P<0.05)。结论:1α-羟化酶质粒转染角质形成细胞可以明显抑制其增殖,促进其分化,诱导其凋亡。1α-羟化酶质粒转染为以增殖过渡分化不全为特征的皮肤病比如银屑病以及某些肿瘤的基因治疗提供了新思路。
AIM:To study the effect of 25-hydroxyvitamin D_3-1α-hydroxylase(1α-hydroxylase for short) plasmid translation on the proliferation differentiation and apoptosis of keratinocyte(KC).METHODS:Translating the keratinocyte grown in serum-free conditions and investigating the morphologic changes and differentiation; using Giemsa dyeing and Tunel to investigate apoptosis induced by plasmid transfected; also using mouse vaginal epithelium in estrus cycle and mouse tail scaled epidermis to study the effect of plasmid transfected in vivo.RESULTS:Translation of 1α-hydroxylase can significantly promote the differentiation of KC and this effect positively depends on the dose of plasmid; and KC can be induced toward apoptosis by the association of 1α-hydroxylase plasmid translation (0.015 μg/μL) and vitamin D_(3) (10^(-6) mol/L).Transfection of 1α-hydroxylase cDNA can very significantly inhibit the mitosis in mouse vaginal epithelium(P<0.01) and significantly promote the formation of granular layer in scale epidermis of mouse tail(P<0.05).CONCLUSION:Transfection of plasmid taking 1α-hydroxylase cDNA can inhibit proliferation of KC,promote differentiation of KC and induce apoptosis,thus providing a new therapy for the treatment of gene cancer and dermal disease of characterized by hyperproliferation and differentiation disorder such as psoriasis.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2005年第3期279-283,共5页
Journal of China Pharmaceutical University
