NFκ-B抑制剂PDTC抑制鼠眼滤过术后瘢痕化的研究

The prevention effect of pyrrolidine dithiocarbamate against scarring of filtering bleb in rats

目的探讨NFκ-B抑制剂四氢化吡咯二硫代氨基甲酸酯(PDTC)在大鼠滤过性手术中抗瘢痕化的作用。方法将24只SD大鼠随机分为阴性对照组、PDTC组、丝裂霉素C(MMC)组3组,双眼均行手术。术后每日观察滤过泡形态及并发症,记录滤过泡存活时间。另取9只SD大鼠,每组3只,单眼手术,7 d后处死,观察滤过泡组织病理学改变。结果滤过泡存活时间,PDTC组为(13.16±2.588)d,MMC组为(13.75±2.352)d,阴性对照组为(10.06±1.806)d,前2组与阴性对照组相比差异均有统计学意义(P<0.01)。术后角膜混浊,MMC组3眼,PDTC组1眼。病理切片显示术后7 d,对照组见较多纤维母细胞及胶原组织。结论PDTC抗瘢痕作用与MMC类似,无明显不良反应,有望成为青光眼术中抗瘢痕增生的辅助用药。

Objective Pyrrolidine dithio-carbamate（PDTC） ,a NF-κB inhibitor,was confirmed to be a inhibitor of nuclear factor kappa B（NF-κB） and can induce apoptosis and suppress the secretion of inflammatory factors. Our previous study has demonstrated its inhibiting effect on Tenon＇ s capsule fibroblasts（TCFS） in SD rats. The purpose of this study was to evaluate the effect of PDTC on the prevention of filtering hleb scarring after anti-glaucoma surgery. Methods Filtration surgery was performed on both eyes of twenty-four female SD rats and divided into three groups,including negative control group,PDTC group and mitomycin C（ MMC ） group, lmol/L PDTC and 0. 4 mg/mL MMC was topically utilized for 5 minutes during the operations in the latter two groups respectively. The postoperative bleb appearance and complications were clinically observed in everyday. The other 9 SD rats were used for the monocular filtration surgery and grouped according to mentioned above. The SD rats were killed and the operative eyes were enucleated for HE staining on day 7 after surgery. Results Bleb survival was （ 13.16 ± 2. 588） days in PDTC group and （13.75 ±2. 352） days in MMC group, showing a longer survival time than control group（ 10.06±1. 806）days （P 〈0. 01 ）. There was no significant difference in survival time of filtering bleb between PDTC group and MMC group （ P = 0. 442）. Postoperative blebs of PDTC group were pallor on the first few days. New vessels grow toward filtering bleb on day 4 -7 after surgery in PDTC group and day 3 -5 in MMC group. Cornea opacity was observed in three eyes in MMC group and one eye in PDTC group. Pathological morphology examination demonstrated that more fibroblasts and collagen fibers were seen in control group compared with PDTC group and MMC group on day 7 after surgery. Conclusion PDTC has a good effectiveness in preventing filtering bleb scarring formation and decreasing complications,showing a similar outcome to MMC. Therefore,PDTC could be a new anti-scar drug in ophthalmology.