汉防己甲素对兔结膜成纤维细胞超微结构和兔眼内组织毒性作用

Effects of tetrandrine on ultrastructure of cultured conjunctival fibroblasts and toxicity to intraocular tissues in rabbit

目的 观察汉防己甲素 (Tet)对兔结膜成纤维细胞超微结构的影响及对兔眼内组织的毒性作用。方法 用含 2、4mg·L-1的Tet作用于体外培养的兔结膜成纤维细胞(RCF) 4 8h ,观察Tet对其超微结构的影响 ;用含 30 0、6 0 0mg·L-1的Tet 0 1mL向兔眼玻璃体腔内注射 ,对照组玻璃体腔内仅注入 0 .1mL生理盐水。观察用药前、用药后 3、14d各组视网膜电流图 (ERG)、视觉诱发电位 (VEP)变化。结果 2mg·L-1Tet作用RCF 4 8h后 ,电镜观察细胞超微结构无改变 ,而 4mg·L-1Tet作用RCF 4 8h后 ,细胞次级溶酶体数量增多 ,呈髓鞘样结构。向兔眼玻璃体腔内注射 30 0、6 0 0mg·L-1Tet 0 .1mL后 ,用药前及用药后 3dERG、VEP与对照组相比均无显著性差异 (P >0 .0 5 ) ;而 6 0 0mg·L-1Tet行玻璃体腔内注射达 14d后 ,ERG、VEP与对照组相比有高度显著性差异 (P <0 .0 0 0 1)。结论 汉防己甲素对兔结膜成纤维细胞生长有一定的毒性作用 ,但适宜浓度的汉防己甲素应用于兔眼内组织防止成纤维细胞增殖是安全的。

Objective To observe the effects of tetrandrine on ultrastructure of cultured rabbit conjunctival fibroblasts(RCF) and the retinal toxicity.Methods Cultured fibroblasts were exposed to different concentration of Tetrandrine solution (2,4 mg·L -1 ).Ultrastructure of RCF were investigated by electromicroscope after exposed to tetrandrine for 48 hours.Fifteen healthy rabbits were divided into 3 groups randomly.Different concentration (300,600 mg·L -1 )of tetrandrine were injected intra-vitreous body and 0.1 mL saline was also injected as control.Retinal toxicity were examined by electroretinogram(ERG) and visual evoked potential(VEP)at the third and fourteenth day after injection.Results Ultrastructure of RCF had no change after exposed to tetrandrine 2mg·L -1 48 hours,but the number of secondary lysosome increased and showed myelinated structure after exposed to tetrandrine 4mg·L -1 48 hours.ERG and VEP had no significant difference between control group and(300 and 600 mg·L -1 )tetrandrine groups before and after intra-vitreous body injection 3 days(P>0.05),but markedly reduced after 600 mg·L -1 intra-vitreous body injection 14 days(P<0.000 1).Conclusion Tetrandrine has cytotoxicity for the growth of RCF but low dose concentration of tetrandrine is safety for inhibit proliferation of rabbit conjunctival fibroblasts and clinical use.