去整合素echistatin对糖尿病兔后发性白内障形成中信号通路PI3-K/Akt和ERK1/2的影响

Effects of disintegrin echistatin on PI3-K/Akt and ERK1 /2 signaling pathways in posterior capsule opacification model of diabetic rabbit

目的观察去整合素echistatin对糖尿病兔后发性白内障形成中信号通路PI3-K/Akt和ERK1/2的影响,从分子水平上探讨echistatin的作用。方法建立糖尿病兔模型(n=24),随机分组并行透明晶状体囊外摘出术,术毕前房分别注入0.2 m L灭菌蒸馏水(对照组,n=12)或0.2 m L 10.0 mg·L^(-1)echistatin溶液(echistatin干预组,n=12)。术后10 d及6周(每个时间点6眼),裂隙灯显微镜观察两组术眼PCO分级情况,同时摘取术眼应用RT-PCR法检测后囊膜上信号因子Akt和ERK1/2 mRNA表达情况。结果术后10 d对照组和echistatin干预组PCO分级比较差异无统计学意义(P=0.093),但echistatin干预组PCO1级眼数少于对照组;术后6周echistatin干预组PCO级别明显低于对照组(P=0.006)。对照组和echistatin干预组Akt mRNA相对表达量术后10 d分别为0.981 7±0.380 4、0.481 7±0.166 5,术后6周分别为0.651 7±0.204 7、0.401 7±0.151 3,echistatin干预组均明显低于对照组(P=0.015,0.037)。对照组和echistatin干预组ERK1/2 mRNA相对表达量术后10 d分别为0.948 3±0.227 5、0.610 0±0.280 6,术后6周分别为0.921 7±0.299 4、0.465 0±0.180 0,echistatin干预组均明显低于对照组(P=0.045,0.009)。结论去整合素echistatin对糖尿病兔后发性白内障的发生和发展有一定的抑制作用,其发生的机制可能与抑制信号因子Akt和ERK1/2表达,进而阻断信号通路PI3-K/Akt和ERK1/2的转导有关。

Objective To investigate the effects of disintegrin echistatin on PI3-K /Akt and ERK1 /2 signaling pathways in the posterior capsule opacification（ PCO） m odel of diabetic rabbit. Meth od s Rabbits were induced diabetic m odel（ n = 2 4）,then accepted extracapsular lens extraction,and injected 0. 2 m L distilled water（ control group; n = 1 2） or 0. 2 m L 1 0. 0 m g · L^-1echistatin（ echistatin-treated group; n =1 2） into the anterior cham ber random ly and intraoperatively. At postoperative1 0 days and 6 weeks,PCO severity of two groups was evaluated with slit lam p m icroscope,and the posterior capsules（ n = 6 for each tim e point） were extracted to analyze the level of Akt and ERK1 /2 m RNA. R esu lts At 1 0 days postoperatively,the num ber of grade 1of PCO in echistatin-treated group was lower than the control group,though there was no significant difference in PCO grades in the two groups（ P = 0. 0 9 3）; At 6 weeks postoperatively,PCO grades of the echistatin-treated group were significantly lower than those of the control group（ P = 0. 0 0 6）. Akt m RNA expression in control group and echistatin-treated group were 0. 9 8 1 7 ± 0. 3 8 0 4 and 0. 4 8 1 7 ± 0. 1 6 6 5 at postoperative 1 0 days,respectively,0. 6 5 1 7 ± 0. 2 0 4 7 and 0. 4 0 1 7 ± 0. 1 5 1 3 at postoperative 6 weeks,respectively,the echistatin-treated group were lower than the control group（ P = 0. 015,0. 037）. ERK1 /2 mRNA expression in control group and echistatintreated group were 0. 9 4 8 3 ± 0. 2 2 7 5 and 0. 6 1 0 0 ± 0. 2 8 0 6 at postoperative 1 0days,respectively,0. 9 2 1 7 ± 0. 2 9 9 4 and 0. 4 6 5 0 ± 0. 1 8 0 0 at postoperative 6weeks,respectively,the echistatin-treated group were lower than the control group（ P =0. 0 4 5,0. 0 0 9）. C on clu sion Echistatin can inhibit diabetic rabbit PCO occurrence and developm ent after extracapsular lens extraction,which m ay be related to down-regu-late the expression of Akt and ERK1 /2,then inhibit the PI3-K / Akt and ERK1 /2 signaling pathways.