3-硝基酪氨酸与糖尿病心肌病大鼠心肌细胞凋亡的关系研究

摘要

AIM : AIM : To explore the relationship between 3 - nitrotyrosine( 3 - NT ) level in hearts or blood and myocardial cell apoptosis in rat diahetic cardiomyopathy( DCM ).METHODS: Sixty Sprague - Dawley( SD ) rats ( male , 8 - week - old ) were randomly divided into 4 groups : normal group, diahetic cardiomyopathy group( DCM group ),diabetic rats treated with valsartan( 40 mg · kg-1 · d-1 , D +V group ) and DCM rats treated with valsartan( 40 mg · kg-1 · d-1 , DCM +V group ).Apoptotic index( AI ) of rat cardiac myocytes was examined hy TUNEL.The expression index ( EI ) of 3 - NT in rat cardiac myocytes was examined hy immunohistochemistry.The 3 - NT concentration in rat serum was examined by ELISA. RESULTS : ( 1 ) Significant differences of the heart weight indexes among the 4 groups were observed ( P ＜0.01 ).The heart weight indexes in DCM group and DCM +V group were higher than those in normal group and D +V group( P ＜ 0.01 ).( 2 ) The EI of 3 - NT in the cardiac myocytes was positively correlated with the AI of the cardiac myocytes in the same group( P ＜0.01 ), but the concentration of 3 - NT in hlood had no correlation with the AI of cardiac myocytes( P ＞ 0.05 ).( 3 ) The difference of AI of cardiac myocytes among the 4 groups had statistical significance( P ＜ 0.01 ).The arrangement from high to low of AI was DCM group ＞ D +V group and DCM +V group ＞ N group( P ＜0.05 ).( 4 )The EI of 3 - NT in DCM group was the highest as compared to other groups( P ＜0.05 ).( 5 ) No statistical difference of 3 - NT concentration in blood aruong the 4 groups was observed( P ＞0.05 ).CONCLUSION: ( 1 ) The expression of 3 NT in DCM myocardial tissues in SD rats is significantly increased and closely correlated with the apoptosis in myocardial cells.Valsartan inhibits 3 - NT expression in DCM myocardial cells, thus inhibits the DCM myocardium apoptosis.( 2 )The 3 - NT level in blood can not be true for reflection of 3 - NT expression in DCM myocardial tissues and its effect on myocardial cell apoptosis.%目的:探讨2型糖尿病大鼠心肌组织及血中3-硝基酪氨酸(3-NT)与糖尿病心肌病(DCM)心肌细胞凋亡的关系.方法:选取8周龄雄性SD大鼠60只,将其随机分为4组,空白对照组、DCM组、糖尿病+缬沙坦处理组和DCM+缬沙坦处理组,每组15只.用TUNEL法检测DCM心肌细胞的凋亡指数(AI);用免疫组化的方法检测心肌组织中3-NT的表达指数(EI);用ELISA法检测血清中3-NT的浓度.结果:(1)4组大鼠的心脏重量指数有显著差异(P＜0.01),DCM组和DCM+缬沙坦处理组心脏重量指数大于空白对照组和糖尿病+缬沙坦处理组. (2)心肌组织免疫组化方法检测表明,心肌组织中3-NT的EI与心肌细胞的AI呈正相关(P＜0.01),而血中3-NT的含量与心肌细胞的AI无相关关系(P＞0.05).(3)4组大鼠间的AI比较有显著差异(P＜0.01).两两比较各组AI,DCM组＞糖尿病+缬沙坦预处理组、DCM+缬沙坦处理组＞空白对照组.(4)4组大鼠心肌组织3-NT表达指数比较有显著差异(P＜0.01);两两比较,DCM组显著大于其它3组.(5)4组大鼠血中3- NT的浓度比较无显著差异(P＞0.05).结论:(1)DCM大鼠心肌组织中3-NT的表达显著增多并与心肌细胞凋亡密切相关,缬沙坦能够抑制DCM大鼠心肌细胞中3-NT的表达,并由此抑制DCM大鼠心肌细胞凋亡.(2)循环血中的3-NT水平不能真实反映DCM大鼠心肌组织中3-NT表达水平及其对心肌细胞凋亡的影响.