大豆异黄酮对糖尿病大鼠心肌钙调控蛋白基因表达的影响

    Influence of soy isoflavones on gene expression of myocardial sarcoplasmic reticulum calcium regulatory proteins in diabetic rats

    • 摘要: 目的:探讨大豆异黄酮对糖尿病大鼠心肌细胞肌浆网钙调控蛋白基因表达的影响。方法:雄性SD大鼠40只,随机分为正常对照(NC)组、糖尿病对照(DC)组、大豆异黄酮治疗(ST)组和尼尔雌醇治疗(NT)组。后3组腹腔注射链脲佐菌素55 mg/kg制备糖尿病模型。第7周起,NC、DC组予0.5%羧甲基纤维素钠10 m.lkg-1.d-1,ST组予大豆异黄酮120 m l.kg-1.d-1,NT组予尼尔雌醇混悬液每周0.2 mg/kg灌胃2次。第12周末记录离体心室内压曲线并分析。取心室肌组织,应用RT-PCR技术测定钙调控蛋白的基因表达。结果:与NC组比,DC组大鼠左心室收缩压、平均压、室内压最大上升/下降速率降低(P<0.01);与DC组比,ST组、NT组以上指标均增高(P<0.01)。而左心室舒张末压,DC组明显高于NC组(P<0.01);ST组、NT组均低于DC组(P<0.01)。与NC组比,DC组大鼠心肌肌浆网Ca2+-ATP酶(SERCA)、兰尼碱受体2型(RyR2)、1,4,5三磷酸肌醇受体2型(IP3R2)mRNA表达降低,但受磷蛋白(PLB)mRNA表达增高(P<0.01)。与DC组比,ST组、NT组大鼠心肌SERCA、RyR2、IP3R2mRNA表达增高,而PLB mRNA表达降低(P<0.01)。结论:大豆异黄酮可以改善糖尿病大鼠左心室功能,可能与其上调心肌SERCA、RyR2、IP3R2mRNA的表达和下调PLB mRNA的表达有关。

       

      Abstract: Objective:To investigate the influence of soy isoflavones on gene expression of myocardial sarcoplasmic reticulum calcium regulatory proteins in diabetic rats.Methods:Forty male Sprague-Dawley rats were randomly divided into four groups:normal control (NC) group,diabetic control (DC) group,soy isoflavones treatment (ST) group and nilestriol treatment (NT) group.All the groups were given streptozotocin (STZ) 55 mg/kg intraperitoneal injection (IP) except NC group.After 6 weeks,soy isoflavones 120 ml·kg-1·d-1 was given to ST group,nilestrioli 0.2 mg/kg to NT group twice a week,and the same CMC-Na was given to NC and DC groups.The volumes to all groups were 2 ml·kg-1·d-1.The drugs were all intragastrically administered using stomach tubes.The left ventricular systolic pressure (LVSP),left ventricular end diastole pressure (LVEDP) and Mean,±dp/dtmax of the rats were recorded at the end of the 12th week.The gene expressions of calcium regulatory proteins were detected by RTPCR.Results:Compared with NC group,the LVSP,LVEDP and Mean,±dp/dtmax of DC group were significantly lower (P<0.01),but those in ST and NT groups were markedly higher than DC group (P<0.01).LVEDP was increased in DC group while it was significantly decreased in ST and NT groups (P<0.01).The mRNA level of sarcoplasmic reticulum Ca2+-ATPase (SERCA),ryanodine receptor type 2 (RyR2) and 1,4,5-triphosphate inositor type 2 (IP3R2) in DC group were sharply decreased compared with that in NC group,but the mRNA level of phospholamban (PLB) was increased (P<0.01).The mRNA's expression of SERCA,RyR2,IP3R2 in ST and NT groups were significantly increased compared with that in DC group,but that of PLB was decreased (P<0.01).Conclusions:Soy isoflavones treatment could improve the heart function of the diabetic rats,which is possibly owing to its up-regulation of the levels of SERCA,RyR2,IP3R2 mRNAs and down-regulation of PLB mRNA.

       

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