糖尿病大鼠血-脊髓屏障紧密连接蛋白claudin-1、claudin-5、ZO-1表达变化  

The changes of tight junction-associated proteins claudin-1,claudin-5 and ZO-1 in diabetic rats

作　　者：周亚军[1] 赵玉武[1] 刘帮健[1] 施弘[1] 薛波[1] 

机构地区：[1]上海交通大学附属第六人民医院神经内科,200233

出　　处：《中国神经免疫学和神经病学杂志》2010年第6期439-442,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：上海市自然科学基金资助项目(编号:07ZR14059)

摘　　要：目的动态观察糖尿病大鼠血-脊髓屏障紧密连接蛋白claudin-1、claudin-5、ZO1表达。方法雄性SD大鼠60只,随机分为糖尿病模型组和正常对照组2组,每组30只,以链脲佐菌素(STZ)腹腔注射建立糖尿病大鼠模型,分别于造模后第15天、30天、90天(各时间点均设对照)取脊髓组织(每次各取6只鼠)以Westernblot和实时荧光定量PCR法检测claudin-1、claudin-5、ZO-1蛋白和mRNA表达。结果 (1)claudin 1、claudin-5蛋白相对表达在糖尿病模型组第30天[分别为(0.324±0.01 5)、(0.289±0.032)]、第90天[分别为(0.220±0.029)、(0.242±0.034)]均较对照组[第30天分别为(0.464±0.009)、(0.475±0.035),第90天分别为(0.468±0.031)、(0.489±0.018)]降低(P<0.01),且糖尿病模型组第15天、30天、90天三时间点claudin-1、claudin-5蛋白表达逐渐降低,差异有统计学意义(P<0.05)。各组均未检出ZO-1表达。(2)claudin-1、claudin-5 mRNA相对表达在糖尿病模型组第30天[分别为(2.67±0.71)×10^(-4) 、(2.87±0.74)×10^(-4)]、第90天[分别为(0.081 4±0.034)×10^(-1)、(0.122±0.027)×10^(-1))]均较对照组[第30天分别为(13.13±3.09)×10^(-1)、(14.81±2.24)×10^(-4),第90天分别为(13.21±1.98)×10 、(1 4.50±2.72)×10^(-4)]降低(P<0.01),且糖尿病模型组第15天、第30天、第90天三时间点mRNA相对表达水平逐渐降低,三时间点差异有统计学意义(P<0.05)。ZO-1 mRNA表达在糖尿病模型组第15天、第30天及第90天[分别为(4.40±1.94)×10^(-1)、(2.33±0.64)×10^(-1)、(2.32±0.45)×10^(-1)]亦均较对照组[分别为(29.89±6.27)×10^(-1)、(30.68±1 7.64)×10^(-1)、(29.27 ±7.55)×10^(-1)]降低(P<0.01)。结论糖尿病可能导致血-脊髓屏障紧密连接蛋白claudin-1、claudin-5、ZO-1表达降低,而且随病程延长claudin-l、claudin-5表达呈逐渐降低趋势。Objective To observe the dynamic changes of tight junctions （TJ） -associated proteins claudin-1, claudin-5, ZO-1 in streptozotocin （STZ） -induced diabetic rats. Methods Sixty male SD rats were randomly divided into normal control group （30 rats） and diabetic group （30 rats）. Diabetes was induced by a single intraperitoneal injection of STZ, the rats were executed on the 15th, 30th, and 90th days after injection, respectively. The expressions of claudin-1, claudin-5, ZO-1 in rat spinal cord were assessed by Western blot and real-time quantitative RT-PCR analyses. Results （1） Compared with the control rats, the protein levels of claudin-land claudin-5 in diabetic group decreased markedly on 30th day [claudin-1 （0. 324±0. 015 vs 0. 464± 0. 009）, claudin-5 （0. 289±0. 032 vs 0. 475±0. 035）, P〈0.01], and reached to the lowest level on the 90th day[claudin-1 （0.220±0.029 vs0.468±0.031）, claudin-5 （0.242±0.034 vs0.489±0.018）, P〈0.017. ZO-1 was not detected in all groups. （2） Compared with the control rats, the mRNA expressions of claudin-land claudin-5 in diabetic group were markedly decreased on the 30th day [claudin-1 [ （2. 67±0.71） ×10^-4 vs （13.13 ±3.09） ×10^-4], claudin-5 [ （2.87±0.74）×10^-4 vs （14.81±2.24）×10^-4 ], P〈0.013, and the 90th day [claudin-1 （0.0814±0.034）×10^-4 vs （13.21±1.98）×10^-4, claudin-5 （0.122±0.027）×10^-4 vs （14.50±2.72）×10^-4 , P〈0.01]. The mRNA expression of ZO-1 was decreased significantly in diabetic group on the 15th day [ （4.40±1.94）×10^-4 vs （29.89±6.27）×10^-4, P〈0.01], the 30th day [ （2.33±0. 642）×10^-4 vs （30. 68±17. 64） ×10^-4, P〈0.01], and the 90th day[ （2.32±0.451）×10^-4 vs （29.27±7.55）×10^-4, P〈0.01]. Conclusions In Diabetes, the expressions of TJ-associated proteins elaudin-1 and claudin-5 in bloodspinal cord barrier decreased gradually along with the course of diabetes at both mRNA and protein levels. The expression of ZO-1 decreased in m

关 键 词：糖尿病 血-脊髓屏障 紧密连接 CLAUDIN ZO-1 

分 类 号：R744.1[医药卫生—神经病学与精神病学]