川芎嗪对视网膜色素变性小鼠干预作用的机制

目的:观察川芎嗪对视网膜色素变性rds小鼠的干预作用和机制。 方法:rds新生小鼠 84只，随机分为实验组和对照组，每组42只小鼠。实验组小鼠从出生时开始，腹腔注射盐酸 川芎嗪80 mg/kg，2次/d，直至生后35 d；对照组同时注射等量生理盐水。分别在用药 后0、3、7、1 4、21、28、35 d取实验组和对照组小鼠眼球，立即经10%中性甲醛固定，常规病理切片。另取眼球经2.5%戊二醛溶液固定，电子显微镜观察。用末端脱氧核苷酸转移酶介导的dUTP缺口标 记技术(TUNEL)方法检测视网膜光感受器细胞的凋亡，用免疫组织化学方法测定bcl-2在视网膜的表达。 结果:病理观察结果显示，经盐酸川芎嗪治疗后14、21、28 、35 d，rds小鼠光感 受器细胞核层数与未用药的对照组相比较，明显增加（P＜0.01）。电子显微镜观察结果显示，川芎嗪可减缓rds小鼠光感受器细胞和视网膜外段盘膜部位线粒体的病变，减少盘膜和外界膜的破坏。rds小鼠经盐酸川芎嗪治疗后3、7、14、21、28、35 d，光感受器细胞凋 亡率比对照组明显减少（P＜0.01）；治疗后3、7、14、21、28、35 d时，bcl -2在视网膜光感受器细胞及光感受器细胞内外段的表达明显增强（P＜0.05） 。 结论:盐酸川芎嗪可延缓rds小鼠视网膜光感受器细胞的减少，其作用机制可能是通过上调视网膜 外核层及光感受器细胞内外段bcl-2的表达延缓rds小鼠视网膜光感受器细胞的凋亡。

Intervention effect of the tetramethylpyrazine on the rds mice with retinitis pigmentosa

Objective:To observe the intervention effect of the tetra methylpyraz ine on the rds mice with retinitis pigmentosa. Methods:A total of 84 rds mice were randomly divided into 2 groups, with 42 mice in each group. The mice in the experimental group underwent intra peritoneal cavity injection with hydrochlor i c tetramethylpyrazine (80 mg/kg, twice per day) at the date of birth and till 35 days after birth, whereas the normal saline was injected into the intra perito n eal cavity of rats in the control group. The mice were sacrificed 0, 3, 7, 14, 2 1, 28, 35 days after birth, and the eyeballs were enucleated for the routine pat hologic examination with the light microscope. The apoptosis of photoreceptor ce ll nuclei was detected by terminal deoxynucleotidyl transferase mediated dUTP n i ck end labeling (TUNEL) technigue and the expression of bcl 2 in retina was de tect by immunohistochemistry method. Results:The results of li ght microscopy s howed that the layer number of retinal photoreceptor cell nuclei with tetramethy lpyrazine treatment was increased 14, 21, 28, 35 days after the treatment compar ed with that in the control group（P＜0.01）. The results of electron-micro scope suggested that tetramethylpyrazine might reduce lesions in the photoreceptor cells and the destruction of the disc member, mitochondrion，and outer limiting me mbrane in the photoreceptor outer segment in rds mice. The apoptosis of the phot oreceptor cell nuclei reduced in rds mice 3, 7, 14, 21, 28 and 35 days after the treatment compared with that in the control group （P＜0.01）. The express ion of bcl-2 in the matrix of retinal photoreceptor cell nuclei and its inner and o u ter segments increased significantly in rds mice 3，7, 14, 21, 28 and 35 days af ter the treatment （P＜0.05）. Conclusions:Tetramethylpyra zine might reduce ret inal photoreceptor apoptosis by up regulating the expression of bcl-2 in the m at rix of retinal photoreceptor cell nuclei or its inner and outer segments in rds mice.