白藜芦醇对高糖诱导乳鼠心肌细胞凋亡和损伤的保护作用

目的观察白藜芦醇对高糖诱导的乳鼠心肌细胞凋亡及损伤的影响，探讨硫氧还蛋白（Trx）系统在此过程中的作用。方法使用培养的乳鼠心肌细胞，随机分为三组：正常对照组（葡萄糖5．5mmol／L）、高糖组（葡萄糖25mmol／L）和高糖＋白藜芦醇组（葡萄糖25．0mmol／L，白藜芦醇30．0umol／L）。白藜芦醇组给予白藜芦醇30umol／L预处理45min，对照组和高糖组均给予等量相应溶剂处理。各组细胞于正常糖浓度DMEM或高糖DMEM中继续培养48h后，收集上清液和细胞裂解液进行后续研究。结果与正常对照组相比，高糖组细胞乳酸脱氢酶漏出和细胞凋亡明显增加。进一步分析发现，高糖组细胞p38激酶活性、细胞内活性氧生成量，丙二醛（MDA）含量和3一硝基酪氨酸生成量明显升高，Trx活性降低，但其表达未见明显改变，其内源性抑制蛋白硫氧还蛋白相关蛋白（TXNIP）表达增加。白藜芦醇预处理显著减轻了高糖诱导的细胞凋亡及损伤，m活性得到改善，高糖引起的TXNIP表达明显下调，细胞p38激酶活性、细胞内活性氧生成、MDA含量、3一硝基酪氨酸生成量明显降低。结论白藜芦醇对高糖诱导的乳鼠心肌细胞凋亡和损伤具有明显保护作用，其机制与白藜芦醇减少Trx的硝基化，抑制高糖诱导的TXNIP表达上调，从而保护Trx的功能，减少自由基损伤和凋亡的发生有关。

Resveratrol protect neonatal rat cardiomyocyte from high glucose induced apoptosis and injury

Objective To investigate whether resveratrol can relieve high glucose induced cardiomyocyte apoptosis and injury, and if so, what is the role of thioredoxin system in this process. Methods Cultured neonatal cardiomyocytes were randomly divided into 3 groups： normal glucose group （5.5 mmol/L）, high glucose group （25 mmol/L） and high glucose （25.0 mmol/L）＋Resveratrol （30.0 umol/L） group, and then subjected to 45 min pretreatment with resveratrol （30.0 umol/L） or vehicle for 45 min followed by cell culture in normal glucose or high glucose DMEM respectively. Cell lysate and supernatant were collected after 48 hour culture for further mea- surement. Results Compared with the normal glucose group, high glucose culture condition induced increased LDH leakage and cell apoptosis, p38 kinase activity, intracellular reactive oxygen species generation, MDA content, 3-nitrotyrosine production and TXNIP expression were increased, while Trx activity was decreased. Resveratrol pretreatment successfully relieved high glucose induced cell injury and apoptosis. Trx activity was recovered and p38 kinase activity, intracellular reactive oxygen species generation, MDA content, 3-nitrotyrosine production and TXNIP expression were decreased markedly. Conclusion Resveratrol could protect the cultured cardiomyoeytesfrom glucotoxicity mediated apoptosis and injury. As a powerful antioxidant, resveratro! could improve Trx function not only by reducing Trx nitration, but also by inhibiting TXNIP up-regulation.