Differential effects of curcumin on vasoactive factors in the diabetic rat heart.
Differential effects of curcumin on vasoactive factors in the diabetic rat heart.
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DOI：
10.1186/1743-7075-3-27
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发表时间：
2006-07-18
影响因子：
4.5
通讯作者：
Chakrabarti, Subrata
中科院分区：
文献类型：
--
作者：
Farhangkhoee, Hana;Khan, Zia A;Chen, Shali;Chakrabarti, Subrata
氧化应激增加与慢性糖尿病并发症的发病机制有关，包括心肌病。最近的研究表明，姜黄素是一种有效的抗氧化剂，可能有助于预防糖尿病引起的氧化应激和随后的继发性并发症。我们研究了姜黄素对心脏组织和培养细胞一氧化氮（NO）通路的影响。用姜黄素治疗链脲佐菌素诱导的糖尿病大鼠1个月。然后分析心脏组织内皮NO合成酶（eNOS）和诱导NO合成酶（iNOS） mRNA的表达。通过免疫组化分析硝基酪氨酸和8-羟基-2'-脱氧鸟苷（8-OHdG）来评估氧化蛋白和DNA损伤。心脏组织进一步受到内皮素-1 (ET-1) mRNA表达的影响。为了进一步表征姜黄素的作用，我们检测了微血管内皮细胞（MVECs）。分别暴露于葡萄糖、葡萄糖和不同浓度的姜黄素中，观察培养的mvec的NOS表达、核因子-κB （NF-κB）和活化蛋白-1 （AP-1）的活性变化。同时检测氧化应激和ET-1表达水平。我们的研究结果表明，一个月的糖尿病导致心脏eNOS和iNOS mRNA水平上调，以及硝基酪氨酸和8-OHdG免疫反应性上调。用姜黄素治疗糖尿病大鼠，降低eNOS和iNOS水平，减少氧化DNA和蛋白质损伤。有趣的是，姜黄素进一步增加了心脏血管收缩剂ET-1。mvec暴露于高糖环境会增加eNOS和iNOS水平以及氧化应激。姜黄素通过核因子-κB和活化蛋白-1对NOS改变和氧化应激具有剂量依赖性。暴露于姜黄素也增加了mvec中ET-1的水平。我们的研究表明姜黄素对心脏血管活性因子表达的不同影响，并表明组织微环境在糖尿病并发症治疗中的重要性。
Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications, including cardiomyopathy. Recent studies indicate that curcumin, a potent antioxidant, may be beneficial in preventing diabetes-induced oxidative stress and subsequent secondary complications. We have investigated the effects of curcumin on the nitric oxide (NO) pathway in cardiac tissues and cultured cells. Streptozotocin-induced diabetic rats were treated with curcumin for a period of one month. Heart tissues were then analyzed for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression. Oxidative protein and DNA damage were assessed by immunohistochemical analysis of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Heart tissues were further subjected to endothelin-1 (ET-1) mRNA expression. In order to further characterize the effects of curcumin, we assayed microvascular endothelial cells (MVECs). Cultured MVECs, exposed either to glucose or glucose and varying concentrations of curcumin, were assessed for alterations of NOS expression and activation of nuclear factor-κB (NF-κB) and activating protein-1 (AP-1). Oxidative stress and ET-1 expression levels were also assayed. Our results indicate that one month of diabetes causes an upregulation of both eNOS and iNOS mRNA levels, and nitrotyrosine and 8-OHdG immunoreactivity in the heart. Treatment of diabetic rats with curcumin reduced eNOS and iNOS levels in association with reduced oxidative DNA and protein damage. Interestingly, curcumin further increased vasoconstrictor ET-1 in the heart. Exposure of MVECs to high glucose increased both eNOS and iNOS levels and oxidative stress. Curcumin prevented NOS alteration and oxidative stress in a dose-dependent manner which was mediated by nuclear factor-κB and activating protein-1. Exposure to curcumin also increased ET-1 levels in the MVECs. Our studies indicate the differential effects of curcumin in vasoactive factor expression in the heart and indicate the importance of tissue microenvironment in the treatment of diabetic complications.