高血糖状态早期治疗的乙醇提取物可抑制糖尿病大鼠模型中的肾小球损伤和血管重塑。
Ethanolic Extract of Treatment in the Early Stage of Hyperglycemia Condition Inhibits Glomerular Injury and Vascular Remodeling in Diabetic Rat Model.
作者信息
Setyaningsih Wiwit A W, Arfian Nur, Fitriawan Akbar S, Yuniartha Ratih, Sari Dwi C R
机构信息
Department of Anatomy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
Department of Nursing, Faculty of Health Sciences, Universitas Respati Yogyakarta, Yogyakarta 55282, Indonesia.
出版信息
Evid Based Complement Alternat Med. 2021 Jul 6;2021:6671130. doi: 10.1155/2021/6671130. eCollection 2021.
BACKGROUND
Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD). Vascular dysfunction is characterized by an imbalance in vasoconstrictor and vasodilator agents which underlies the mechanism of vascular injury in DM. Additionally, diminished podocytes correlate with the severity of kidney injury. Podocyturia often precedes proteinuria in several kidney diseases, including diabetic kidney disease. (CeA) is known as an anti-inflammatory and antioxidant and has neuroprotective effects. This research aimed to investigate the potential effect of CeA to inhibit glomerular injury and vascular remodeling in DM.
METHODS
The DM rat model was induced through intraperitoneal injection of streptozotocin 60 mg/kg body weight (BW), and then rats were divided into 1-month DM (DM1, = 5), 2-month DM (DM2, = 5), early DM concurrent with CeA treatment for 2 months (DMC2, = 5), and 1-month DM treated with CeA for 1-month (DM1C1, = 5). The CeA (400 mg/kg BW) was given daily via oral gavage. The control group (Control, = 5) was maintained for 2 months. Finally, rats were euthanized and kidneys were harvested to assess vascular remodeling using Sirius Red staining and the mRNA expression of superoxide dismutase, podocytes marker, ACE2, eNOS, and ppET-1 using RT-PCR.
RESULTS
The DM groups demonstrated significant elevation of glucose level, glomerulosclerosis, and proteinuria. A significant reduction of SOD1 and SOD3 promotes the downregulation of nephrin and upregulation of TRPC6 mRNA expressions in rat glomerular kidney. Besides, this condition enhanced ppET-1 and inhibited eNOS and ACE2 mRNA expressions that lead to the development of vascular remodeling marked by an increase of wall thickness, and lumen wall area ratio (LWAR). Treatment of CeA, especially the DMC2 group, attenuated glomerular injury and showed the reversal of induced conditions.
CONCLUSIONS
treatment at the early stage of diabetes mellitus ameliorates glomerulosclerosis and vascular injury via increasing antioxidant enzymes.
背景
糖尿病（DM）的特征是氧化应激、炎症和血管功能障碍，这些会导致糖尿病肾病，进而发展为终末期肾病（ESRD）。血管功能障碍的特点是血管收缩剂和血管舒张剂失衡，这是DM血管损伤机制的基础。此外，足细胞减少与肾损伤的严重程度相关。在包括糖尿病肾病在内的几种肾脏疾病中，足细胞尿通常先于蛋白尿出现。（CeA）具有抗炎和抗氧化作用，并具有神经保护作用。本研究旨在探讨CeA对抑制DM肾小球损伤和血管重塑的潜在作用。
方法
通过腹腔注射链脲佐菌素60mg/kg体重（BW）建立DM大鼠模型，然后将大鼠分为1个月DM组（DM1，n = 5）、2个月DM组（DM2，n = 5）、早期DM并同时接受CeA治疗2个月组（DMC2，n = 5）和1个月DM并用CeA治疗1个月组（DM1C1，n = 5）。通过口服灌胃每天给予CeA（400mg/kg BW）。对照组（Control，n = 5）维持2个月。最后，对大鼠实施安乐死并采集肾脏，使用天狼星红染色评估血管重塑，并使用逆转录聚合酶链反应（RT-PCR）检测超氧化物歧化酶、足细胞标志物、血管紧张素转换酶2（ACE2）、内皮型一氧化氮合酶（eNOS）和前内皮素-1（ppET-1）的mRNA表达。
结果
DM组血糖水平、肾小球硬化和蛋白尿显著升高。超氧化物歧化酶1（SOD1）和超氧化物歧化酶3（SOD3）的显著降低促进了大鼠肾小球肾中nephrin的下调和瞬时受体电位阳离子通道蛋白6（TRPC6）mRNA表达的上调。此外，这种情况会增加ppET-1并抑制eNOS和ACE2 mRNA表达，从而导致以壁厚增加和管腔壁面积比（LWAR）增加为特征的血管重塑的发展。CeA治疗，尤其是DMC2组，减轻了肾小球损伤，并显示出诱导状况的逆转。
结论
糖尿病早期治疗通过增加抗氧化酶改善肾小球硬化和血管损伤。
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