姜黄素对糖尿病大鼠心脏血管活性因子的不同作用。
Differential effects of curcumin on vasoactive factors in the diabetic rat heart.
作者信息
Farhangkhoee Hana, Khan Zia A, Chen Shali, Chakrabarti Subrata
机构信息
Department of Pathology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
出版信息
Nutr Metab (Lond). 2006 Jul 18;3:27. doi: 10.1186/1743-7075-3-27.
BACKGROUND
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.
METHODS
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-kappaB (NF-kappaB) and activating protein-1 (AP-1). Oxidative stress and ET-1 expression levels were also assayed.
RESULTS
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-kappaB and activating protein-1. Exposure to curcumin also increased ET-1 levels in the MVECs.
CONCLUSION
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.
背景
氧化应激增加与包括心肌病在内的慢性糖尿病并发症的发病机制有关。最近的研究表明，姜黄素作为一种有效的抗氧化剂，可能有助于预防糖尿病诱导的氧化应激及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中一氧化氮（NO）途径的影响。
方法
用链脲佐菌素诱导糖尿病大鼠，并用姜黄素治疗一个月。然后分析心脏组织中内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）的mRNA表达。通过硝基酪氨酸和8-羟基-2'-脱氧鸟苷（8-OHdG）的免疫组织化学分析评估氧化蛋白和DNA损伤。进一步检测心脏组织中内皮素-1（ET-1）的mRNA表达。为了进一步明确姜黄素的作用，我们检测了微血管内皮细胞（MVECs）。将培养的MVECs暴露于葡萄糖或葡萄糖与不同浓度的姜黄素中，评估一氧化氮合酶表达的变化以及核因子-κB（NF-κB）和激活蛋白-1（AP-1）的激活情况。还检测了氧化应激和ET-1表达水平。
结果
我们的结果表明糖尿病一个月会导致心脏中eNOS和iNOS的mRNA水平上调，以及硝基酪氨酸和8-OHdG免疫反应性增加。用姜黄素治疗糖尿病大鼠可降低eNOS和iNOS水平，并减少氧化DNA和蛋白质损伤。有趣的是，姜黄素进一步增加了心脏中的血管收缩剂ET-1。将MVECs暴露于高葡萄糖中会增加eNOS和iNOS水平以及氧化应激。姜黄素以剂量依赖的方式预防一氧化氮合酶改变和氧化应激，这是由核因子-κB和激活蛋白-1介导的。暴露于姜黄素还会增加MVECs中的ET-1水平。
结论
我们的研究表明姜黄素对心脏中血管活性因子表达有不同影响，并表明组织微环境在糖尿病并发症治疗中的重要性。
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