通心络胶囊对糖尿病小鼠视网膜IKKβ/IKBα/NF-κB通路的作用  

Effects of Tongxinluo capsule on retina through IKKβ/IKBα/NF-κB pathway in diabetic mouse

作　　者：王杏[1] 王超[1] 邢邯英[1] 刘敏[1] 张哲[1] 

机构地区：[1]河北省人民医院老年医学重点实验室,河北省石家庄市050051

出　　处：《眼科新进展》2014年第11期1005-1008,共4页Recent Advances in Ophthalmology

基　　金：国家重点基础研究发展计划项目(973计划)(编号:2012CB518600)~~

摘　　要：目的观察通心络胶囊对糖尿病小鼠视网膜IKKβ/IKBα/NF-κB通路的影响。方法 40只KK/Upj-Ay小鼠随机分为模型组、通心络低(1 g·kg-1)、中(2 g·kg-1)、高(4 g·kg-1)剂量组,每组各10只,10只C57BL/6小鼠为对照组。通心络组按相应剂量灌胃给药,对照组和模型组给予等体积的蒸馏水,每天1次,连续12周。测定体质量、空腹血糖值(fasting blood glucose,FBG),伊文思蓝法(evans blue method,EB)测定血-视网膜屏障的通透性,HE染色法观察视网膜形态学变化,Real-time PCR(qPCR)和Western blot法测定IKKβ、IKBα、NF-κB mRNA和蛋白的表达及P-IKBα和核NF-κB蛋白的表达。结果通心络高剂量组较中、低剂量组细胞结构更致密,排列更有序。通心络低、中、高剂量组EB含量分别(20.82±3.88)ng·mL-1、(16.43±2.60)ng·mL-1、(16.14±2.42)ng·mL-1,较模型组(25.53±3.57)ng·mL-1明显下降(均为P<0.05)。通心络中、高剂量组IKKβmRNA和蛋白表达量较模型组显著下降(均为P<0.01);通心络组IKBαmRNA,通心络中、高剂量组IKBα蛋白以及PIKBα蛋白的表达均较模型组显著下降(均为P<0.01),通心络低、中、高剂量组核NF-κB蛋白表达量为0.52±0.05、0.43±0.05、0.34±0.04,显著低于模型组(0.61±0.07)(均为P<0.05)。结论通心络胶囊可明显改善KK/Upj-Ay小鼠视网膜病变,其机制与抑制IKKβ/IKBα/NF-κB通路相关。Objective To investigate the effects of Tongxinluo（ TXL） capsule on IKKβ /IKBα / NF-κB pathway of retina in diabetic mouse. Methods Forty KK /Upj-Ay mice were randomly divided into model group,TXL low-dose group（ TXL-L,1 g·kg^-1）,medium group（ TXLM,2 g · kg^-1）,high group（ TXL-H,4 g·kg^-1）,10 cases in each group,and another 10C57 BL /6 mice were selected in the control group. The TXL groups were given drug with corresponding dose by oral administration,meanwhile control group and model group were given distilled water of equal volume,once a day in the ensuing 12 weeks. Body weight and fasting blood glucose were detected,and blood-retinal barrier permeability were determined by evans blue（ EB）method. The morphological changes of retinal were observed by HE staining. The expression levels of IKKβ,IKBα,NF-κB mRNA and protein,P-IKBα and nuclear NF-κB protein,in retina were measured by real-time PCR and Western Blot. Results The cells of the retina in TXL-H group were arranged more compact and more orderly than TXL-L and TXL-M groups. The EB content in TXL groups were（ 20. 82 ± 3. 88） ng·mL^-1,（ 16.43 ±2.60） ng·mL^-1 and（ 16. 14 ± 2. 42） ng·mL^-1,respectively,which were lower significantly than that in the model group（ 25. 53 ±3.57） ng·mL^-1（ all P〈0.05）. Compared with the model group,the mRNA and protein levels of nucleur IKKβ were reduced obviously in TXL-M and TXL-H group（ all P〈0. 01）,and the protein levels of IKBα and P-IKBα were decreased in the TXL-M and TXL-H group（ all P〈0. 01）.The expression levels of NF-κB protein in TXL groups were 0. 52 ± 0. 05,0. 43 ± 0. 05,0. 34 ± 0.04,respectively,which were lower than the model group（ 0. 61 ± 0. 07）（ all P〈0. 05）. Conclusion TXL capsule can significantly improve KK / Upj-Ay mice diabetic retinopathy and the mechanism is related with inhibition of IKKβ / IKBα /NF-κB pathway.

关 键 词：通心络胶囊 糖尿病视网膜病变 IKKβ/IKBα/NF-κB 

分 类 号：R739.65[医药卫生—肿瘤]