丙戊酸钠对视网膜色素变性小鼠光感受器细胞的保护作用

Neuroprotective Effect of Sodium Valproate on Photoreceptor Cell in rd Mice

观察在视网膜变性小鼠(retinal degeneration mouse,rd小鼠)视网膜色素变性过程中,丙戊酸钠(valproate sodium,VPA)是否对光感受细胞具有保护作用。取48只新生rd小鼠,随机分为VPA组和正常对照组,每组24只。(1)VPA组,出生后每日以VPA100mg/kg的剂量进行腹腔注射;(2)对照组,出生后每日腹腔注射与VPA相同体积的生理盐水。于出生后7天、14天、21天、28天分别将VPA组和对照组的6只小鼠处死,取眼球做冰冻切片,行HE染色,对两组视网膜光感受器细胞数进行计数,并测量外核层厚度;用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(terminal deoxy-nucleotidyl transferase-mediated dUTP nick-end labeling,TUNEL法)检测凋亡细胞数,并对凋亡细胞数目进行统计分析。结果显示:(1)出生后7天VPA组光感受器细胞数和外核层厚度与对照组相比并无统计学差异,出生后14天、21天、28天,VPA组光感受器细胞和外核层厚度多于对照组,两者具有统计学差异(P<0.05);(2)两组光感受器细胞均于出生后7天开始出现凋亡,在出生后7天、14天VPA组外核层凋亡数少于对照组,两者具有统计学差异。提示VPA具有对抗视网膜色素变性小鼠光感受器细胞凋亡的作用,能延缓光感受器细胞的进行性退变。

To explore whether sodium valproate （VPA） can protects photoreceptor cells on a mouse model of retinitis pigmentosa, 48 rd mice were divided into VPA group and Normal Control group at random, 24 in each group. VPA group received intraperitoneal injection of VPA 100mg/kg （10ml/kg） while the control group received saline 10ml/kg every day from the postnatal day 1 （ P1 ）. Six mice were sacrificed at P7, P14, P21 and P28 respectively. Eyeballs were enucleated, and cut into frozen section and measured the number of photoreceptor cells and the thickness of outer nuclear layer （ONL） by HE. Apoptotic cells in the section were counted by terminal deoxynucleotidyl transferase dUPT nick-end labeling （TUNEL）. Differences between two groups were analyzed by statistic method. The results showed that the number of photoreceptor cells and thickness of ONL were observed in mice at P7 and no difference was found in two groups. The number of survived photoreceptor cells and the thickness of ONL in the VPA group were more than that in the control group at P14, P21, P28 （ P 〈 0.05 ）. Apoptosis of photoreceptor cells in both groups were observed since PT. The number of apoptotic cells in VPA group at PT, P14, and P28 were significantly less than that in Normal Control group. The resuits indicate that VPA appears to protect photoreceptor cells from apoptosis in the stage of the retinitis pigmentosa, and delays retinal degeneration.