丹参单体、三氟拉嗪防治兔眼增生性玻璃体视网膜病变的实验研究

Experimental study of IH764-3 and trifluoperazine on preventing proliferative vitreoretinopathy in rabbit eyes

目的评价丹参单体和三氟拉嗪对实验性兔增生性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)的防治作用。方法有色兔81只随机分为6组:A至C组为药物防治组,E至G组为药物毒性观察组;从A至C组、E至G组中兔另一非实验眼分别选对照组:D组和H组。A至D组眼内注入视网膜色素上皮(retinal pigment epithelial,RPE)细胞后分别注入三氟拉嗪、丹参单体、三氟拉嗪加丹参单体混合液、磷酸盐缓冲液;E至H组注入磷酸盐缓冲液后分别注入三氟拉嗪、丹参单体、三氟拉嗪加丹参单体混合液、磷酸盐缓冲液。通过间接检眼镜观察A至D组玻璃体混浊、视网膜脱离情况,通过间接检眼镜、光学显微镜观察E至H组视网膜病理学改变。结果给药后1d,A组发生Ⅱ级玻璃体混浊8眼,B组Ⅱ级玻璃体混浊6眼,C组Ⅱ级玻璃体混浊7眼,D组Ⅱ、Ⅲ级玻璃体混浊各10眼,3个实验组与D组相比差异均有显著统计学意义(均为P=0.00)。给药后3d,A组Ⅱ级玻璃体混浊3眼,B组及C组未见发生Ⅱ级及以上玻璃体混浊,D组Ⅱ级玻璃体混浊10眼、Ⅲ级玻璃体混浊6眼,3个实验组与D组相比差异也均有统计学意义(均为P=0.00)。给药后5d,A组、B组及C组均未见发生Ⅱ级及以上玻璃体混浊,D组Ⅱ级玻璃体混浊8眼,3个实验组与D组相比差异均有统计学意义(均为P<0.05)。给药后5d,D组Ⅱ级PVR8眼、Ⅲ级PVR2眼,3个实验组无PVR发生,差异均有统计学意义(均为P<0.05)。给药后7d,D组Ⅱ级PVR14眼、Ⅲ级PVR6眼,各实验组无PVR发生,差异也均有统计学意义(均为P<0.05)。给药后14d,A组Ⅱ级PVR3眼,B及C组各有Ⅱ级PVR2眼,D组Ⅱ级PVR2眼、Ⅲ级PVR16眼、Ⅳ级PVR2眼;3个实验组与D组相比差异均有统计学意义(均为P=0.00)。给药后21d,D组Ⅲ级PVR12眼、Ⅳ级PVR8眼;3个实验组PVR发生情况无变化,3个实验组与D组比较差异均有统计学意义(均为P=0.00)。给药后28d,D组Ⅳ级PVR14眼、Ⅲ级PVR6眼,3个实验组PVR发生情况无变化,所有实验组与D组比较,差异也均有统计学意义(均为P=0.00)。E至H组在整个观察期内未见毒性病理学改变。结论三氟拉嗪、丹参单体、三氟拉嗪与丹参单体联合可有效预防实验性PVR。

Objective To investigate the effect of IH764-3 and trifluoperazine on the prevention and treatment of proliferative vitreoretinopathy（PVR） in experimental rabbit models.Methods Eighty one pigmented rabbits were divided into 8 groups randomly.Group A to group D were established for drug prevention groups,while group E to group G were for drug toxicity observation groups.Control eye groups（group D and group H） were made from group A to group C and group E to group G.Rabbits in group A to group D were injected with trifluoperazine（TFP）,IH764-3,combination of trifluoperazine and IH764-3,as well as PBS respectively after the injection of retinal pigment epithelium cells（RPE） intravitreously.Rabbits in group E to group H were injected with trifluoperazine,IH764-3,combination of trifluoperazine and IH764-3,PBS respectively after the injection of PBS.The morbidity of traction retinal detachment and vitreous turbidity in group A to group D were monitored by ophthalmoscope.The toxic damages of the drugs in group E to group H were monitored by ophthalmoscope and light microscopy.Results On the first day after medicine administration,there were 8 cases of grade Ⅱvitreous turbidity in group A,6 cases in group B,7 cases in group C and 10 cases of grade Ⅱ and 10 cases of grade Ⅲ in group D,which showed significant differences between 3 experimental groups and group D（all P=0.00）.On the 3rd day after drug administration,there were 3 cases of grade Ⅱvitreous turbidity in group A,no vitreous turbidity occured in group B and group C,10 of grade Ⅱand 6 cases of grade Ⅲ respectively in group D,which showed significant differences between 3 experimental groups and group D（all P=0.00）.On the 5th day after medicine administration,there was no occurrence of vitreous turbidity in group A,group B and group C,8 cases of vitreous turbidity of grade Ⅱin group D,showing significant differences between 3 experimental groups and group D（all P0.05）.On the 5th day after medicine administration,there was no occurrence of PVR in 3 experimental groups,while 8 cases of grade ⅡPVR and 2 cases of grade Ⅲ PVR in group D,showing significant differences between 3 experimental groups and group D（all P0.05）.On the 7th day after medicine administration,there were still no occurrence of PVR in the experimental groups,while 14 of grade ⅡPVR and 6 cases of grade Ⅲ PVR in group D,showing significant differences between 3 experimental groups and group D（all P0.05）.On the 14th day after medicine administration,there were 2 cases of grade Ⅱand 16 cases of grade Ⅲ,as well as 2 cases of grade Ⅳ PVR in group D,while there were only 3 cases of grade Ⅱ PVR in group A and 2 cases of grade Ⅱ PVR in group B and 2 cases of grade Ⅱ PVR in group D,showing significant differences between 3 experimental groups and group D（all P=0.00）.On the 21st day after medicine administration,there were 12 cases of grade Ⅲ and 8 cases of grade Ⅳ PVR in group D,while no change of PVR occurrence in the 3 experimental groups,showing significant differences between 3 experimental groups and group D（all P=0.00）.On the 28th day after medicine administration,there were 6 cases of grade Ⅲ and 14 cases of grade Ⅳ PVR in group D,while PVR occurrence in 3 control group with no change,showing significant differences between 3 experimental groups and group D（all P=0.00）.No evidence of toxicity was found in group E to group H.Conclusion Trifluoperazine,IH764-3 and the combination of trifluoperazine and IH764-3 have significant preventive effect on experimental PVR.