补骨合剂对全反式维甲酸诱导的骨髓基质细胞凋亡的保护作用  

Effect of Bugu Mixture on all-trans retinoic acid-induced apoptosis of bone marrow stromal cells

作　　者：李楠[1] 王和鸣[1] 林旭[2] 郑良朴[3] 沈霖[4] 林一萍[5] 周琳瑛[6] 钟秀容[6] 林芳[7] 

机构地区：[1]福建中医学院骨伤系,福建福州350003 [2]福建医科大学分子医学中心,福建福州350004 [3]福建中医学院医学实验中心,福建福州350003 [4]华中科技大学同济医学院附属协和医院,湖北武汉430022 [5]福建省中医药研究院中医基础研究室,福建福州350003 [6]福建医科大学电镜室,福建福州350004 [7]福建医科大学附属协和医院血液病研究所,福建福州350005

出　　处：《中西医结合学报》2004年第5期367-371,共5页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金资助项目(No.30271630)福建省卫生厅资助项目(No.2002-201)

摘　　要：目的:应用体外培养骨髓基质细胞,在细胞和分子水平观察补骨合剂对细胞凋亡的影响,探讨补骨合剂治疗骨质疏松症的机制。方法:分离SD大鼠骨髓基质细胞,通过形态学方法和流式细胞术检测凋亡细胞周期和线粒体膜电位改变以及Bcl-2、Bax蛋白基因表达,对补骨合剂在细胞凋亡过程中的作用进行评价。结果:补骨合剂的早期应用可以使阻滞于G0/G1期的细胞减少,进入S期进行DNA合成的细胞增多;诱导凋亡的细胞在补骨合剂组Bcl-2表达明显高于全反式维甲酸(all-transretinoicacid,ATRA)诱导组,而Bax表达明显低于ATRA诱导组,且补骨合剂组线粒体的膜电位下降均显著低于ATRA诱导组。结论:补骨合剂治疗骨质疏松症的机制是补骨合剂的早期应用可以使ATRA诱导的凋亡细胞减少,从而促进细胞有丝分裂,抑制细胞凋亡;对骨髓基质细胞线粒体膜上的Bcl-2具有保护作用,同时通过阻止Bax从胞浆中移至线粒体膜上而使Bcl-2在与Bax形成的同源二聚体中占据优势来阻止线粒体膜上的通透性转换孔道开放,从而阻止线粒体释放凋亡诱导因子造成的线粒体膜电位改变和生物合成的破坏,达到抑制凋亡的目的。Objective: We used the SD rat's bone marrow stromal cells (BMSCs) cultured in vitro to observe the effects of Bugu Mixture on the apoptosis and to explore the molecular biologic mechanism of the treatment of osteoporosis with Bugu Mixture. Methods: BMSCs were separated from the bones of the extremities of SD rats in vitro. The morphologic changes, the apoptosis cell cycles, the mitochondrion membrane potential changes, and the Bcl-2 and Bax gene expression were observed, and the effects of Bugu Mixture on the course of cell apoptosis were evaluated. Results: The earlier use of Bugu Mixture could decrease the cells blocked in G0/G1 phase, and promote their synthesis of DNA in S phase. The expression of Bcl-2 was higher in the Bugu Mixture group than that in the all-trans retinoic acid(ATRA) induced group, and the expression of Bax was lower in the Bugu Mixture group than that in the ATRA induced group. The mitochondrion membrane potential descended significantly in the Bugu Mixture group than that in the ATRA induced group. Conclusion: The mechanism of the treatment of osteoporosis with Bugu Mixture is that the earlier use of Bugu Mixture can decrease the amount of apoptostic cells induced by ATRA, thus promoting the cell mitosis and restraining the apoptosis. It can also act as a protector to Bcl-2 located on the mitochondrion membrane. By preventing the transferring of the Bax protein from cell-plasm to mitochondrion membrane, it takes the advantage of Bcl-2 in forming Bcl-2/Bax homodimer so as to prevent the opening of the permeability transition pore to avoid the changing of mitochondrion membrane potential and the destruction of biosynthesis caused by the mitochondrion release of apoptosis inducing factors and to reach the objective of restraining apoptosis.

关 键 词：补骨合剂 骨髓基质细胞 诱导 ATRA 治疗 全反式维甲酸 保护作用 目的 转换 方法 

分 类 号：R96[医药卫生—药理学]