雷帕霉素在兔眼滤过性手术中的抗瘢痕作用  

Anti-scarring effect of rapamycin in rabbits following glaucoma filtering surgery

作　　者：康欣 申颖[1] 赵海霞[1] 王召格[1] 关文英[1] 葛瑞春[1] 王瑞芳[1] 邰雪 KANG Xin;SHEN Ying;ZHAO Haixia;WANG Zhaoge;GUAN Wenying;GE Ruichun;WANG Ruifang;TAI Xue(Center of Myopia,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学附属医院近视眼激光治疗中心,内蒙古呼和浩特010050

出　　处：《南方医科大学学报》2018年第11期1389-1394,共6页Journal of Southern Medical University

基　　金：内蒙古自治区卫生和计划生育委员会科研计划项目(201702078);内蒙古自治区自然科学基金面上项目(2011MS1137)

摘　　要：目的探讨雷帕霉素在兔眼滤过性手术中抑制瘢痕的作用。方法取健康成年的青紫兰兔96只,雌雄不限,左眼行小梁切除术后随机分为4组,3组对照组,1组实验组,每组24只。术后实验组左眼分别滴1%、3%、5%的雷帕霉素,对照组左眼滴药用蓖麻油,4次/d。监测眼压并观察结膜、角膜、前房、晶状体情况。常规HE染色,免疫组化方法标记PCNA(抗增殖细胞核抗原)观察滤过道成纤维细胞增殖情况。将RTFs进行体外培养,检测不同浓度(0、0.06、0.25、1、4mg/L)的雷帕霉素处理成纤维细胞后caspase-3,caspase-8,caspase-9的表达变化。结果术后各实验组较对照组眼压低,各时间点实验组PCNA阳性细胞数低于对照组,均具有显著性差异(P<0.05)。采用不同浓度的雷帕霉素处理后,caspase-3,caspase-9的mRNA表达量和蛋白的相对表达量随着雷帕霉素浓度的增加而增加(P<0.001),表现出浓度依赖性。但是caspase-8的mRNA表达量和蛋白相对表达量与对照组相比却未表现出显著的差别(P>0.05)。结论雷帕霉素具有抑制兔青光眼滤过术后滤过道中成纤维细胞过分增生,减少瘢痕形成的作用,还可以通过增加caspase-3和caspase-9的表达诱导RTFs细胞凋亡的发生。Objective To study the anti-scarring effect of rapamycin in rabbits receiving glaucoma filtering surgery. Methods Ninety-six Chinchilla rabbits were randomized equally into 3 rapamycin treatment groups and one control group. All the rabbits underwent trabeculectomy, after which the rabbits in the 3 rapamycin groups were treated with eye drops containing1%, 3%, or 5% rapamycin in the operated eyes, and those in the control groups were given castor oil 4 times a day. The intraocular pressure(IOP) and inflammatory reaction in the treated eyes were observed, and the PCNA-positive cells in the filtering bleb were detected using immunohistochemistry. RTFs isolated from the Tenon’s capsule of the rabbits were cultured in vitro, and the expressions of caspase-3, caspase-8, and caspase-9 in the fibroblasts were detected after treatment with different concentrations of rapamycin. Results The IOP was significantly lower in rapamycin-treated group than in the control group after the surgery(P<0.05). The counts of the PCNA-positive cells were significantly lower in rapamycin-treated rabbits than in the control group(P<0.05). Rapamycin treatment dose-dependently increased the expressions of caspase-3 and caspase-9 at both the mRNA(P<0.001) and protein(P<0.001) levels without causing significant changes in the expressions of caspase-8.Conclusion Rapamycin can inhibit excessive proliferation of the fibroblasts in the filtering bleb to reduce scar formation after glaucoma filtration surgery in rabbits. Rapamycin also increases the expressions of caspase-3 and caspase-9 to induce apoptosis of the RTFs.

关 键 词：雷帕霉素 青光眼 滤过手术 抗瘢痕 细胞凋亡 

分 类 号：R779.6[医药卫生—眼科]