吲哚美辛防治增殖性玻璃体视网膜病变的实验研究

Therapeutic Effect of Indomethacin on Experimental Proliferative Vitreoretinopathy

目的研究玻璃体腔内注射吲哚美辛(indomethacin,IN)对兔增殖性玻璃体视网膜病变(PVR)的防治作用,并评价其对视网膜的毒性.方法防治实验15只健康有色成年兔分为3组(每组5只10只眼):对照组、低剂量组、高剂量组.兔眼玻璃体腔内注入富含血小板的血浆制作PVR动物模型.术后1d,对照组玻璃体腔内注入溶剂无水乙醇,低剂量组注入含5mgIN的无水乙醇溶液,高剂量组注入含7.5mgIN的无水乙醇溶液.给药后7、14、21、28d分别行眼底检查并记录玻璃体腔内PVR的增殖程度.处死动物,抽取玻璃体及剪取玻璃体中的增殖条带,TUNEL法检测凋亡细胞,400倍光镜下计数各组的凋亡细胞数.毒性实验5只健康有色成年兔共10只眼行闪光视网膜电图检查(FERG)后玻璃体腔内注入含7.5mgIN的无水乙醇溶液,28d后行FERG检查,对给药前后的a波和b波的潜伏期及波幅进行统计分析.处死动物,取视网膜组织行透射电镜检查.结果防治实验:术后7d3个组间的PVR的增殖程度无差别(χ2=6.00P≥0.05),术后14、21、28d,与对照组相比,低剂量组和高剂量组的PVR的增殖程度均比对照组低(P<0.05),但高剂量与低剂量组间的PVR增殖程度无差异(P>0.05).高剂量与低剂量组的凋亡细胞数比对照组明显增多(P<0.01),但治疗组间的凋亡细胞数无差异(P>0.05).毒性实验:玻璃体腔内注射IN后28d,FERG的a波、b波的潜伏期延长(P<0.05),波幅降低(P<0.01).透射电镜示:视网膜有一定的改变.结论吲哚美辛能使实验性PVR模型的增殖程度降低,并能诱导PVR形成时玻璃体中及增殖膜上的增殖细胞凋亡.玻璃体腔内注射IN7.5mg时,对视网膜存在一定的毒性作用.

Objective To investigate the therapeutic effect of intravitreal administration of indomethacin on experimential proliferative vitreoretinopathy （PVR） , and also to study the toxicity of indomethacin on retina in the pigment rabbits. Methods The rapeutic effect of indomethacin： Fifteen pigment rabbits were divided randomly and evenly into three groups ： high-dose group, low-dose group, control group. In the first three groups, rabbit eyes were intravitreally injected platelet-rich plasma to induce the experimential proliferative vitreoretinopathy. One day later, animals in high-dose group were intravitreally injected alcohol containing 7.5 mg indomethacin, and in low-dose, 5 mg indomathin. Alcohol was intravitreally administrated in the control-group. After injection,PVR changes were evaluated according to Fastenserg method on 7, 14, 21, 28 days. On 28 days, eyes were enucleated, vitreous fluids and proliferative vitreous membranes were prepared to be stained by TdT-mediated biotin-dUTP nick-end labeling （TUNEL） method for detection of apoptosis cells. Apotosis cells have been numbered under the light microscope. Toxicity of indomethacin on retina： 10 eyes of 5 rabbits were intravitreally injected 0.1 mL alcohol containing 7.5 mg indomethacin. The amplitudes （Aa, Ab） and latent times （La, Lb） of a, b-wave of F-ERG were recorded before injection and after 28 days. 28 days later, eyes were enucleated. Retina were prepared for electron-microscopic examination. Result The rapeutic effect of indomethacin ： The proliferative degrees of the first three groups showed no differences on 7 days after injection （ χ 2 = 6.00 P〉0.05 ）. On 14, 21, 28 days, the differences of proliferative degrees of PVR were observed. The proliferative changes in the treated groups were fewer compared with those in control group respectively （P 〈 0.05）. But there was no difference of proliferative degree between the treatment groups （P 〉 0.05 ）. Compared to the control respectively, the number of apoptosis cells of the treated groups significantly increased （P 〈 0.01 ）.But there was no difference of apoptosis cell number between the treated groups （P 〉 0.05）. Toxicity of indomethacin on retina： Both La and Lb were significantly prolonged after injection （P 〈 0.05 ）. Both Aa and Ab were significantly decreased （P 〈 0.01 ）. The electron-microscopic examination showed that the uhrastructure of retina was slightly changed. Conclusion Intravitreal administration of indomethacin can decrease the proliferative changes of experimential proliferative vitreoretinopathy induced by platelet-rich plasma and also can induce apoptosis of proliferative cells in vitreous and proliferative membrane. There are some toxic effects on the retina when 7.5 mg indomethacin is injected into vitreous cavity.