The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China.
Oxid Med Cell Longev. 2020 Mar 11;2020:7805393. doi: 10.1155/2020/7805393. eCollection 2020.
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing all over the world, which is also the leading cause of end-stage renal failure. Hydroxysafflor yellow A (HSYA) is the main active chemical component of Carthamus tinctorius L., and it is commonly used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the renal protective effects and molecular mechanisms of HSYA on high-fat diet (HFD) and streptozotocin- (STZ-) induced DN in rats. The DN rats were treated with HSYA for eight weeks. We assessed creatinine (CR), urea nitrogen (UN), glomerular volume, podocyte number, renal inflammation, oxidative stress, and cells apoptosis markers after HSYA treatment. The number of apoptotic cells was measured by the TUNEL assay, and apoptosis-related proteins BAX, caspase-3, and BCL-2 in the renal tissue were analyzed by western blot. The treatment with HSYA significantly decreased fasting blood glucose, CR, UN, and blood lipid profile, including triglyceride and total and low-density lipoprotein cholesterol, even though it did not change the rats' body weights. The western blot results indicated that HSYA reversed the upregulation of BAX and caspase-3 and significantly increased BCL-2 in renal tissue. Moreover, the levels of TNF- and the inflammatory products, including free fatty acids (FFA) and lactic dehydrogenase (LDH) in the HSYA group, were significantly decreased. For the oxidative stress marker, the superoxide dismutase (SOD) markedly increased in the HSYA treatment group, while the malondialdehyde (MDA) in the serum and kidney tissue evidently decreased. In conclusion, HSYA treatment preserved kidney function in diabetic nephropathy in the HFD- and STZ-induced rats. The potential mechanism of renal protective effect of HSYA might be through inhibiting oxidative stress, reducing inflammatory reaction, and attenuating renal cell apoptosis. Our studies present a promising use for Hydroxysafflor yellow A in the treatment of type 2 diabetes mellitus.
糖尿病肾病（DN）是糖尿病的严重并发症，其患病率在全球范围内呈上升趋势，也是终末期肾衰竭的主要原因。羟基红花黄色素 A（HSYA）是红花的主要活性化学成分，在中国常用于治疗心血管和脑血管疾病。本研究旨在探讨 HSYA 对高脂肪饮食（HFD）和链脲佐菌素（STZ）诱导的糖尿病肾病大鼠的肾脏保护作用及其分子机制。DN 大鼠用 HSYA 治疗 8 周。我们评估了 HSYA 治疗后肌酐（CR）、尿素氮（UN）、肾小球体积、足细胞数量、肾脏炎症、氧化应激和细胞凋亡标志物。通过 TUNEL 检测法测量凋亡细胞的数量，并通过 Western blot 分析肾脏组织中凋亡相关蛋白 BAX、caspase-3 和 BCL-2。HSYA 的治疗显著降低了空腹血糖、CR、UN 和血脂谱，包括甘油三酯和总胆固醇及低密度脂蛋白胆固醇，尽管它没有改变大鼠的体重。Western blot 结果表明，HSYA 逆转了 BAX 和 caspase-3 的上调，并显著增加了肾脏组织中的 BCL-2。此外，HSYA 组 TNF-α和炎症产物（包括游离脂肪酸（FFA）和乳酸脱氢酶（LDH））的水平显著降低。对于氧化应激标志物，超氧化物歧化酶（SOD）在 HSYA 治疗组中明显增加，而血清和肾脏组织中的丙二醛（MDA）明显减少。总之，HSYA 治疗可保护 HFD 和 STZ 诱导的糖尿病肾病大鼠的肾功能。HSYA 肾脏保护作用的潜在机制可能是通过抑制氧化应激、减少炎症反应和减轻肾细胞凋亡。我们的研究为羟基红花黄色素 A 治疗 2 型糖尿病提供了有希望的应用前景。
