Yang Hong-Wei, Chen Xiao-Long, Liu Zhe-Li, Liu Jie, Bu Li-Min
Department of Ophthalmology, the Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
Int J Ophthalmol. 2010;3(2):120-4. doi: 10.3980/j.issn.2222-3959.2010.02.06. Epub 2010 Jun 18.
To detect the effect of connective tissue growth factor (CTGF) on the apoptosis in the diabetic retina with small interfering RNAs (siRNA) targeting CTGF.
A total of 60 rats were divided into 6 groups including control group, diabetic 4, 8, 12, 16 weeks groups, and interference group. Diabetic rats were induced by intraperitoneal streptozotocin (STZ). Retinas were obtained from control, diabetic rats and diabetic rats of interference group treated by intravitreal injection of CTGFsiRNA to suppress the expression of CTGF mRNA. Retinal cells apoptosis was detected by Tunnel staining and mRNA expression of CTGF was analyzed by RT-PCR.
The levels of CTGF and the apoptosis in the retinas of diabetic rats were significantly higher than those in the controls. Apoptosis occurred at 4 weeks after a diabetic model being set up, became serious with the diabetes developing, while CTGF elevated at 8 weeks. The apoptosis cell counts increased to 25.8cells/mm(2) at 24weeks of diabetes. SiRNA-mediated inhibition of CTGF mRNA resulted in a significant decrease in apoptosis. Significant correlations were found between CTGF and apoptosis in the retina.
It was suggested that CTGF might be involved in retinal cells apoptosis which is a characteristic of early diabetic retina. SiRNA targeting CTGF seems to have the advantage of ameliorating retinal cells apoptosis.
利用靶向结缔组织生长因子(CTGF)的小干扰RNA(siRNA)检测其对糖尿病视网膜细胞凋亡的影响。
60只大鼠分为6组,包括对照组、糖尿病4周、8周、12周、16周组及干扰组。腹腔注射链脲佐菌素(STZ)诱导大鼠糖尿病模型。分别从对照组、糖尿病大鼠及经玻璃体注射CTGF siRNA抑制CTGF mRNA表达的糖尿病干扰组大鼠获取视网膜。采用Tunnel染色检测视网膜细胞凋亡,应用RT-PCR分析CTGF的mRNA表达。
糖尿病大鼠视网膜中CTGF水平及细胞凋亡率均显著高于对照组。糖尿病模型建立4周后出现细胞凋亡,且随糖尿病病程进展而加重,CTGF在8周时升高。糖尿病24周时凋亡细胞计数增加至25.8个/mm²。siRNA介导的CTGF mRNA抑制导致细胞凋亡显著减少。视网膜中CTGF与细胞凋亡之间存在显著相关性。
提示CTGF可能参与糖尿病早期视网膜特征性的细胞凋亡过程。靶向CTGF的siRNA似乎具有改善视网膜细胞凋亡的优势。