环孢霉素A抗增殖作用的实验研究

Experimental study on the inhibiting effects of cyclosporine A on the cell proliferation

目的 通过环孢霉素A(cyclosporine A,CsA)与丝裂霉素C(mytomycin C,MMC)进行对比研究,用免疫组织化学方法,探讨CsA在抗青光眼滤过性手术中的抗增殖作用。方法 25只50眼健康新西兰大白兔随机分为3组,均行小梁切除术。术中分别在Tenon's囊和巩膜之间放置浸有20g·L^(-1)CsA、0.2g·L^(-1)的MMC和生理盐水(normalsaline,NS)海绵片4min,用NS 100mL充分冲洗干净。分别在术后1、4、7、14和28d检查眼压、滤过泡、角膜和眼底情况,取滤过泡及周围组织作病理检查,并用免疫组织化学方法观察成纤维细胞的增殖情况。结果 CsA组和MMC组增殖细胞核抗原(proliferation cellnuclear antigen,PCNA)阳性细胞出现较晚,细胞总数低于NS组。CsA组和MMC组之间无明显差异;CsA组和MMC组眼压多控制在1.93kPa((1kPa=7.5mmHg))以下,形成功能性滤过泡;CsA无明显副作用,MMC组可见角膜混浊及前房反应。结论 CsA能抑制成纤维细胞的增殖,有助于功能性滤过泡的形成,有效控制术后眼压,和MMC组相比无明显差异,值得推广应用。

Objective To investigate the inhibiting effects of cyclosporine A(CsA)on the cell proliferation in wound healing following experimental filtration surgery in rabbit eyes. Methods In a prospective randomized control experimental study, 25 New Zealand white rabbits randomly divided into 3 different groups. They were underwent bilateral trabeculectomy. Before preparations of a half-thickness scleral flap,20g L-1 CsA,0.2g L-1 mytomycin C(MMC) and balanced salt solution were applied on episclera for 4 minutes. The area was irrigated with 100mL balanced salt solution. At 1,4,7,14 and 28 days after surgery ,the filtering blebs were observed, the filtering site was examined by light microscope, and the expresion of proliferation cell nuclear antigen (PCNA) was also examined with immunohistochemical methods. Results In the MMC and CsA-treated eyes, immunoreactive cells appeared the 4th day after surgery and decreased markedly at around 14 days. The number of immunoreative cells in the treated eyes was much lower than that in controls that received balanced salt solution. There was no significant difference between the CsA-treated groups and the MMC-treated groups. In CsA-treated and MMC-treated eyes, the intraocular pressure( IOP) after operation was under 1. 93 kPa(1kPa= 7. SmmHg), the functioning blebs were observed without fibrosis of conjunctive tissue. In control group the effects on the IOP were lower than that of CsA-treated and MMC-treated groups. Conclusion CsA suppress the proliferation of fibroblasts in the filtering site, decrease the IOP after surgery and have effects on the formation of the functioning blebs. CsA have a better effect on inhibiting proliferation and have fewer side effects, so it is worth improving its use.