环孢素A对晚期糖尿病大鼠多器官的保护作用  

Protective effects of cyclosporine A on multiple organs in diabetic rats at advanced stage

作　　者：姜丽娟[1] 戴红双 尹晓梅 孔伟[1] 李菁爽[4] 王华[4] 张云霞[4] 盛艳丽[4] 黄晓玲[4] 韩会民[1] 

机构地区：[1]大庆市第四医院内分泌科,黑龙江大庆163700 [2]大庆市医学高等专科学校,黑龙江大庆163700 [3]深圳市宝安区中心医院,广东深圳518100 [4]大庆龙南医院,黑龙江大庆163700

出　　处：《中国中西医结合急救杂志》2015年第5期472-477,共6页Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care

基　　金：黑龙江省自然科学基金资助项目（D200832）

摘　　要：目的 观察晚期糖尿病（DM）大鼠肝、肾、肺、心肌、主动脉、视网膜的病理学改变,以及环孢素A（CsA）对上述器官是否具有保护作用.方法 30只Wistar雄性大鼠按随机数字表法分为CsA组、DM模型组、正常对照组（CON组）3组,每组10只.采用一次性腹腔注射链脲佐菌素（STZ）55 mg/kg的方法制备晚期DM大鼠模型,48 h后取尾静脉血测血糖,2次血糖均〉16.7 mmol/L为制模成功.CsA组于饲养28周时给予CsA 3 mg·kg^-1·d^-1 6周;CON组不做任何处理.全部动物成模34周后处死取肝、肾、肺、主动脉、心肌、视网膜,采用苏木素-伊红（HE）染色、Masson染色观察病理学改变,用免疫组化染色检测上述器官免疫球蛋白（IgG、IgA）及核转录因子-κB（NF-κB）、转化生长因子-β1（TGF-β1）表达水平的变化.结果 DM模型组大鼠死亡 1只,CsA组死亡2只,分别以9只、8只纳入统计学分析.①HE染色：DM模型组肝小叶结构紊乱,肾小球体积明显肥大,肺泡隔增宽,主动脉管壁中可见淋巴细胞浸润,心肌细胞肥大,视网膜内核层、外核层细胞排列紊乱;CsA组上述变化较DM模型组减轻.②Masson染色：DM模型组肝小叶内可见散在的胶原纤维沉积,肾小球内胶原明显增多,肺间质胶原纤维明显增多,主动脉、心肌胶原纤维增多,视网膜未见明显阳性反应;CsA组上述变化减轻.③ 免疫组化分析显示：与CON组比较,DM模型组肝、肾、肺、主动脉、心肌、视网膜IgG、IgA、NF-κB、TGF-β1表达〔均用吸光度（A）值表示〕均明显增多;与DM模型组比较,CsA组各指标表达均降低 （肝：IgA：110 059±22 321比151 055±12 481,IgG：106 265±39 225比158 296±65 723,NF-κB：95 638±6 045比130 650±9 257,TGF-β1：102 856±10 631比263 380±75 264;肾：IgA：37 305±8 340比53 281±5 412, IgG：35 521±9 310比77 092±8 953,NF-κB：37 768±2 622比54 888±2 494,TGF-β1：48 425±1 170比62 687±8 593;肺：IgA：94 022±1 701比198Objective To observe the pathological changes of liver, kidney, lung, myocardia, aorta and retina in rats with advanced diabetes mellitus （DM）, and whether cyclosporine A （CsA） having the protective effects on the above organs.Methods Thirty male Wistar rats were randomly divided into CsA group, DM model group and normal control group （CON group） by random number table method, 10 rats in each group. Intra-peritoneal injection of streptozotocin （STZ） 55 mg/kg once was performed to prepare an advanced DM model. Forty-eight hours later, venous blood was collected from a tail vein and blood glucose was tested twice, and when the blood sugar was 〉16.7 mmol/L twice, the modeling was successful. All the rats were fed for 28 weeks, afterwards in CsA group, CsA 3 mg·kg^-1·d^-1 was given orally for 6 weeks, while in CON group, no treatment was applied. All the rats were sacrificed at 34 weeks after modeling, and the liver, kidney, lung, aorta, myocardium, retina were taken for hematoxylin-eosin （HE） stain and Masson stain to observe the pathological changes, and the expression levels of IgG, IgA, nuclear factor-κB （NF-κB） and transforming growth factor-β1 （TGF-β1） in the above organs were detected by the immunohistochemical staining and semi-quantitative analysis.Results There was 1 rat dead in DM model group and 2 rats dead in CsA group, therefore 9 rats in former group and 8 rats in latter group were included in the statistical analysis. ① HE staining： in the DM model group, there were hepatic lobular structural disorder, marked hypertrophy of glomerular volume, widening of alveolar septum, lymphocyte infiltration in the wall of aorta, hypertrophy of myocardia, arrangement disorder of retinal inner and outer nuclear layers, while the above changes in CsA group were milder compared with those in model group. ② Masson staining： in DM model group, there were scattered collagen deposition in hepatic lobules, significant increase of collagen in glomeruli and pulmonary interstitium,

关 键 词：糖尿病 环孢素A 免疫球蛋白 核转录因子-ΚB 转化生长因子-Β1 

分 类 号：R587.2[医药卫生—内分泌]