糖尿病兔后囊膜混浊发生过程中血清及房水中AGE和IGF-1的变化及去整合素echistatin对二者的影响

Levels of AGE and IGF-1 in serum and aqueous humor of posterior capsular opacification models in diabetic rabbits and effects of disintegrin echistatin on them

目的观察糖尿病兔后囊膜混浊(posterior capsule opacification,PCO)发生过程中血清及房水中晚期糖基化终末产物(advanced glycation end products,AGE)和胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)的含量变化,同时观察去整合素echistatin(Ecs)对二者的干预作用。方法将24只兔随机分为对照组、糖尿病组及Ecs组,后2组应用四氧嘧啶建立糖尿病模型,所有兔行晶状体摘出术,Ecs组术中晶状体囊袋内注入10 mg·L-1Ecs,其余2组注入等量高压灭菌蒸馏水。分别于术后10 d、6周提取3组血清及房水,应用ELISA法检测AGE和IGF-1含量。结果术后10 d房水中AGE浓度在三组中分别为(0.189±0.200)μg·L-1、(0.467±0.190)μg·L-1、(0.527±0.130)μg·L-1;6周为(0.255±0.640)μg·L-1、(0.716±0.340)μg·L-1、(0.830±0.330)μg·L-1。术后10 d血清中AGE浓度在对照组、糖尿病组和Ecs组中分别为(0.074±0.013)μg·L-1、(0.270±0.120)μg·L-1、(0.213±0.690)μg·L-1;6周为(0.054±0.010)μg·L-1、(0.166±0.460)μg·L-1、(0.149±0.200)μg·L-1。术后10 d房水中IGF-1浓度在3组中分别为(0.279±0.080)μg·L-1、(0.914±0.130)μg·L-1、(0.556±0.290)μg·L-1;6周为(0.176±0.030)μg·L-1、(0.508±0.040)μg·L-1、(0.367±0.090)μg·L-1。术后10 d血清中IGF-1浓度在对照组、糖尿病组和Ecs组中分别为(0.075±0.030)μg·L-1、(0.293±0.160)μg·L-1、(0.305±0.160)μg·L-1;6周为(0.032±0.020)μg·L-1、(0.833±0.570)μg·L-1、(0.788±0.530)μg·L-1。术后10 d及6周对照组血清及房水中AGE和IGF-1含量均低于糖尿病组及Ecs组(均为P<0.05)。糖尿病组及Ecs组中AGE含量比较,差异均无统计学意义(均为P>0.05),糖尿病组及Ecs组中IGF-1含量在血清中差异均无统计学意义(均为P>0.05),但在房水中Ecs组IGF-1含量明显低于糖尿病组(P=0.003、0.031)。结论 AGE和IGF-1可能促进了糖尿病兔PCO的发生和发展,降低房水中IGF-1的含量可能是去整合素Ecs抑制PCO发展的机制之一。

Objective To investigate the levels of advanced glycation end products （AGE） and insulin-like growth factor-1 （IGF-1） in serum and aqueous humor of posterior capsular opacification in diabetic rabbits, and observe the effects of disintegrate echistatin （Ecs） on them. Methods Twenty-four New Zealand white rabbits were randomly divided into three groups：control group, diabetic group and Ecs group. The rabbits of diabetic group and Ecs group were treated with ear vein injection of alloxan. The rabbits of control group were given the same volume of sterilization distilled water. After the model constructed, all the rabbits were implemented lens extraction surgery. During the surgery,the rabbits of control group and diabetic group were injected with sterilization distilled water into lens capsular bags and the Ecs group was injected with 10 mg·L^-1 Ecs. The serum and aqueous humor of rabbits were extracted at 10 days and 6 weeks after surgery,and the levels of AGE and IGF-1 were determined using enzyme-linked immunosorbent assay （ELISA） technique. Results Ten days after surgery, AGE concentration in serum of the control group, diabetes group and Ecs group were （0.074 ±0. 013） μg·L^-1 , （0. 270 ±0. 120） μg·L^-1 , （0.213 ±0.590）μg·L^-1 ,respectively,which at 5 weeks after surgery were （ 0. 054 ±0. 010 ）μg·L^-1, （ 0. 155± 0.450）μg·L^-1, （0. 149 ±0. 200） μg·L^-1 ,respectively. Ten days after surgery,AGE concentration in aqueous humor of the control group, diabetes group and Ecs group respectively were （0. 189 ±0. 200）μg·L^-1, （0. 467 ± 0. 190） μg·L^-1, （0. 527 ± 0. 130） μg·L^-1 ,respectively,which at 6 weeks after surgery were （0. 255 ±0. 540）μg·L^-1 , （0. 715 ±0.340）μg·L^-1 , （0.830 ±0.330） μg·L^-1,respectively. Ten days after surgery,IGF-1 concentration in serum of the control group ,diabetes group and Ecs group respectively were （0.075 ±0.030） μg·L^-1, （0.293 ±0. 160）μg·L^-1 , （0.305 ±0. 160） μg·L^-1 ,respectively,which at 6 weeks after surgery were （0.032 ±0. 020） μg·L^-1, （0.833 ±0.570）μg·L^-1 , （0.788 ±0.530）μg·L^-1 ,respectively. Ten days after surgery,IGF-1 concentration in aqueous humor of the control group,diabetes group and Ecs group respectively were （0. 279 ± 0. 080）μg·L^-1 , （0. 914 ± 0. 130）μg·L^-1 ,（0.556 ±0.29）μg·L^-1 ,respectively,which at 6 weeks after surgery were （0. 176 ±0. 030）μg·L^-1, （0. 508±0.040）μg·L^-1 , （0. 367 ±0.090）μg·L^-1 ,respectively. The levels of AGE and IGF-1 in serum and aqueous humor of rabbits in control group at 10 days or 6 weeks after surgery were lower than those in diabetic group and Ecs group（ all P 〈 0.05 ）. There was no difference in AGE levels in serum or aqueous humor between diabetic group and Ecs group （ all P〉0. 05）. The IGF-1 levels in aqueous humor in Ecs group was lower than those in diabetic group （P =0. 003,0. 031 ） ,but there was no difference in serum between two groups （ all P 〉0.05）. Conclusion AGE and IGF-1 may promote the occurrence and development of posterior capsular opacification in diabetic rabbits,and lower IGF-1 levels in the aqueous humor may be one of the mechanisms that disintegrin Ecs inhibiting the development of posterior capsular opacification in diabetic rabbits.