Netrin-1对糖尿病视网膜病变大鼠的保护作用

目的　探讨Netrin-1对糖尿病视网膜病变（diabetic retinopathy，DR）大鼠的保护作用。方法　通过腹腔注射链脲佐菌素诱导DR大鼠模型，使用生理盐水作为对照。为了研究Netrin-1基因沉默对DR的影响，构建si-NC和si-Netrin-1大鼠模型，并随机分为4组:A组（si-NC大鼠）、B组（si-Netrin-1大鼠）、C组（si-NC大鼠+DR造模）、D组（si-Netrin-1大鼠+DR造模）。为了研究外源性Netrin-1对DR的影响，将WT大鼠随机分为3组:对照组、DR组、Netrin-1组。造模后3个月，HE染色检测各组大鼠视网膜组织各层厚度，免疫荧光染色检测Iba1表达情况，实时荧光定量PCR检测各炎症因子表达水平。结果　与C组相比，D组大鼠视网膜组织中内核层、外核层厚度降低，差异均有统计学意义（均为 P<0.05）；Iba1及IL-1β、IL-6、IL-12、TNF-α表达升高，差异均有统计学意义（均为P<0.05）。与DR组相比，Netrin-1组内核层、外核层厚度升高，差异均有统计学意义（均为 P<0.05）；Iba1及各炎症因子表达水平降低，差异均有统计学意义（均为P<0.05）。结论　Netrin-1基因沉默可加重糖尿病大鼠视网膜损伤和炎症，外源性Netrin-1则具有保护作用。

Protective effect of Netrin-1 on rats with diabetic retinopathy

Objective To explore the protective effect of Netrin-1 on rats with diabetic retinopathy(DR).Methods The DR rat models were constructed by intraperitoneal injection of streptozotocin,and normal saline was used as control.To study the effect of Netrin-1 gene silencing on DR,si-NC and si-Netrin-1 rats were constructed and randomly divided into 4 groups:Group A(si-NC rats),group B(si-Netrin-1 rats),group C(si-NC rats+DR modeling)and group D(si-Netrin-1 rats+DR modeling).To study the effect of exogenous Netrin-1 on DR,WT rats were randomly divided into 3 groups:Control group,DR group and Netrin-1 group.Three months after modeling,the thickness of retinal tissues at each layer were measured by HE staining,the expression of Iba1 was detected by immunofluorescence staining,and the levels of inflammatory factors were measured by real time fluorescence quantitative PCR.Results Compared with group C,the thickness of inner nuclear layer and outer plexiform layer decreased,the expression of Iba1 and levels of IL-1β,IL-6,IL-12 and TNF-αincreased in group D,and statistical differences were observed(all P<0.05).Compared with DR group,the thickness of inner nuclear layer and outer plexiform layer in Netrin-1 group increased,and the expression of Iba1 and levels of inflammatory factors decreased,and statistical differences were observed(all P<0.05).Conclusion Netrin-1 gene silencing can aggravate retinal injury and inflammation in diabetic rats,while exogenous Netrin-1 has protective effect.