靶向抑制GLUT1對糖尿病視網(wǎng)膜病變中視錐細胞的保護作用
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本文關(guān)鍵詞: 葡萄糖轉(zhuǎn)運蛋白- RNA 小分子干擾 糖尿病視網(wǎng)膜病變 視錐細胞 出處:《第三軍醫(yī)大學(xué)學(xué)報》2014年15期 論文類型:期刊論文
【摘要】:目的觀察抑制視網(wǎng)膜上葡萄糖轉(zhuǎn)運蛋白-1(glucose transporter-1,GLUT1)對糖尿病視網(wǎng)膜病變中視錐細胞的影響。方法 27只8周齡C57BL/6小鼠按隨機數(shù)字表法分為正常對照組、糖尿病對照組和GLUT1小干擾核糖核酸(siRNA)治療組。腹腔注射鏈脲佐菌素建立糖尿病模型后,GLUT1 siRNA治療組予以玻璃體腔注射靶向GLUT1的siRNA,正常對照組和糖尿病對照組注射等量非靶向性siRNA,以上操作每2周重復(fù)注射1次,共注射9次。建模第18周3組小鼠行明適應(yīng)視網(wǎng)膜電圖檢查視錐細胞功能,免疫熒光共定位法和免疫印跡法檢查視網(wǎng)膜GLUT1的表達,測定比較視網(wǎng)膜含糖量,通過免疫熒光共定位法檢查視錐細胞的密度及形態(tài)改變。結(jié)果與糖尿病對照組相比,GLUT1 siRNA治療組小鼠視網(wǎng)膜GLUT1表達明顯下調(diào),較正常對照組下降68.51%(P0.01)。盡管糖尿病對照組和GLUT1 siRNA治療組視網(wǎng)膜組織含糖量均高于正常對照組,但GLUT1 siRNA治療組小鼠視網(wǎng)膜含糖量比糖尿病對照組低42.67%,差異有統(tǒng)計學(xué)意義(P0.01);糖尿病對照組和GLUT1 siRNA治療組小鼠的明適應(yīng)視網(wǎng)膜電圖的a波及b波振幅均低于正常對照組,但GLUT1 siRNA治療組較糖尿病對照組分別高47.59%和42.61%,差異有統(tǒng)計學(xué)意義(P0.01);形態(tài)學(xué)檢查發(fā)現(xiàn)糖尿病對照組較GLUT1 siRNA組視錐細胞排列稀疏,外節(jié)形態(tài)更為短小。結(jié)論 GLUT1 siRNA通過抑制GLUT1表達,限制轉(zhuǎn)運葡萄糖進入視網(wǎng)膜,降低視網(wǎng)膜局部含糖量從而對光感受器視錐細胞產(chǎn)生保護作用。
[Abstract]:Objective To observe the inhibition of retinal glucose transporter -1 (glucose transporter-1 GLUT1) effect on diabetic retinopathy in cone cells. Methods: 27 C57BL/6 mice aged 8 weeks were randomly divided into normal control group, diabetic control group and GLUT1 small interfering ribonucleic acid (siRNA) treatment group by intraperitoneal injection of streptozotocin. Streptozotocin diabetic model was established after GLUT1 siRNA treatment group received intravitreal injection of GLUT1 targeting siRNA, normal control group and diabetic control group was injected with non targeting siRNA, the above operation was repeated every 2 weeks 1 injections, 9 injections. Eighteenth weeks of modeling, 3 groups of mice for photopic electroretinogram cone cell function, expression and Western blotting examination of retinal GLUT1 colocalization of immunofluorescence, determination of retinal sugar content, by immunofluorescence co localization method of density of cone cells and shape inspection State change. Results compared with diabetes control group, GLUT1 siRNA treatment group mice retinal GLUT1 expression was significantly lowered compared with normal control group decreased 68.51% (P0.01). Although the diabetic control group and GLUT1 treatment group siRNA retinal tissue sugar content were higher than the normal group, but GLUT1 siRNA treated mice retina than the diabetic control group with low sugar content 42.67%, the difference was statistically significant (P0.01); diabetes control group and GLUT1 siRNA group were photopic electroretinogram a wave and b wave amplitude were lower than the normal control group, but the GLUT1 siRNA treatment group than the diabetic control group were respectively 47.59% and 42.61%, the difference was statistically significant (P0.01); morphological examination found that diabetes control compared with group GLUT1 group siRNA cones are sparse, the outer segment morphology is more short. Conclusion GLUT1 siRNA through inhibiting the expression of GLUT1, glucose transport into the optic network Limited The membrane, which reduces the local sugar content in the retina, protects the photoreceptor cones.
【作者單位】: 南昌大學(xué)第二附屬醫(yī)院眼科;
【基金】:江西省教育廳青年科學(xué)基金(GJJ13046)~~
【分類號】:R587.2;R774.1
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