目的：研究环孢素A对白内障术后晶状体上皮细胞增殖过程中磷酸肌醇-3激酶(phosphatidylinositol-3 kinase，PI-3k)途径的影响，为后发性白内障的治疗提供实验依据。

方法：将健康白色家兔30只60眼，行双眼透明晶状体皮质吸除术，右眼为治疗组，左眼为对照组。 术后第1d起，对照组眼用生理盐水点眼6次，而治疗组眼应用1%环孢素A(cyclosporine A， CsA)眼药水点眼6次。分别在术后第1d未点药前、术后1wk，2wk，1mo和2mo各处死随机选择的6只兔，摘取双眼球。应用免疫组织化学、原位杂交方法检测赤道部晶状体上皮细胞中增殖细胞核抗原(proliferating cell nuclear antigen，PCNA)及张力蛋白同源的28号染色体缺失磷酸酯酶mRNA(PTEN mRNA)和Ser473-R的表达。

结果：术后两组PCNA和Ser473-R的表达均逐渐降低，其中1wk(0.690±0.035 vs 0.785±0.015，t=6.099，P<0.01)和2wk(0.571±0.038 vs 0.670±0.037，t=4.585，P<0.01)时治疗组PCNA表达均显著低于对照组。另外，1wk(0.374±0.031 vs 0.435±0.030，t=3.486，P=0.006 )和2wk(0.220±0.022 vs 0.251±0.020，t=2.516，P=0.031)时治疗组Ser473-R的表达均显著低于对照组。术后1wk～1mo时，两组PTEN mRNA均逐渐回升。术后1wk，治疗组A值显著高于对照组(0.302±0.027 vs 0.255±0.038，t=2.474，P=0.033)。

结论：环孢素A对兔眼白内障术后晶状体上皮细胞增殖过程中PI-3k途径有显著抑制作用，为研究CsA抑制后发性白内障提供实验依据。

AIM: To investigate the effect of cyclosporine A(CsA)on the phosphatidylinositol-3 kinase(PI-3k)pathway during procession of proliferation in epithelial cells of rabbit lens, and provide treatment strategies for after cataract on the basis of experiment.

METHODS: Sixty eyes of 30 healthy white rabbits were operated by lens cortex removal in cataract surgery, and 30 right eyes were divided in treatment group and the other 30 eyes were divided in control group. From the first postoperative day, the control group eyes were dropped with normal saline 6 times each day, and the treatment group eyes were dropped with 1% CsA 6 times each day. Six rabbits were selected randomly and killed on the day before dropping and 1, 2wk, 1 and 2mo of postoperative day respectively. The lens of those killed rabbits were removed by surgery. The strategies of immunohistochemistry and mount in situ hybridization were used to detect the content of proliferating cell nuclear antigen(PCNA), gene of phosphate and tension homology deleted on chromsome ten(PTEN)mRNA, Ser473-R, respectively.

RESULTS: The expression of PCNA and Ser473-R were both down-regulate after operation in treatment group and control group, and the PCNA levels were significantly lower among treatment group than those in control group on 1wk(0.690±0.035 vs 0.785±0.015, t=6.099, P<0.01)and 2wk(0.571±0.038 vs 0.670±0.037, t=4.585, P<0.01). In addition, the levels of Ser473-R were significantly lower among treatment group than those in control group on 1wk(0.374±0.031 vs 0.435±0.030, t=3.486, P=0.006)and 2wk(0.220±0.022 vs 0.251±0.020, t=2.516, P=0.031). However, the expression levels of PTEN mRNA were continually increased 1wk～1mo after operation, in which the expression levels of PTEN mRNA were significantly higher among treatment group than those in control group on 1wk(0.302±0.027 vs 0.255±0.038, t=2.474, P=0.033).

CONCLUSION: 1% CsA could inhibit the proliferation of epithelial cells in lens of rabbits with after cataract through preventing PI-3k pathway.

中国辽宁省自然科学基金项目(No.201102259)