目的:虽然氧化应激是驱动糖尿病肾病(DN)的关键因素,坚定的血糖控制仍然是支柱预防措施。由于其富含抗氧化剂,因此被广泛描述为有效的降血糖和降血脂药。因此,本报告旨在评估在糖尿病肾病(DN)模型中马齿胺种子的甲醇(MO)和二氯甲烷(MC)固定油提取物的肾脏保护潜力.
方法:使用无水甲醇和二氯甲烷提取马齿胺种子,和1型糖尿病是用单一55mg/kg剂量的链脲佐菌素(STZ)溶解在100mmol/L柠檬酸盐缓冲液(pH4.5)诱导,然后糖尿病动物接受MO,MC,连续42天比较其相对于参考药物“氯沙坦”的抗糖尿病作用。每周评估肾功能和DN生物标志物,并通过RT-PCR定量糖尿病肾脏中不同氧化应激介质的相对表达。使用GraphPadPrism9.0.2对数据进行统计分析。
结果:口服MO和MC提取物(250mg/kg/天)显着改善了体重减轻(P<0.0001/个),空腹血糖水平(FBG)(P<0.0001/每个),尿量(P<0.0001/个),以及血清肌酐(P<0.0001/个),尿酸(P=0.0022,0.0052),和血尿素氮(BUN)(P=0.0265,0.0338);与未经治疗的糖尿病大鼠相比。此外,两种提取物都恢复了糖尿病肾脏抗氧化机制的有效性,如ROS积累和脂质过氧化的显着减少所表明的;更高的GSH含量,并促进谷胱甘肽还原酶和超氧化物歧化酶抗氧化酶的活性(P<0.0001/各)。组织学上,两种提取物都减轻了DN结构改变,包括肾小球充血和肾小管变性,MC处理的肾脏显示接近正常结构。所有治疗肾脏的转录谱显示TNF-α的表达显著下调,IL-6,Keap1和NF-κB基因,同时SDF-1、IL-10、Nrf2、HO-1和PPARγ基因表达显著上调(P<0.0001/all)。
结论:这些发现强调了马齿轮轴提取物通过中和高血糖诱导的ROS积累介导的显著的预防DN的潜力,绕过下游的炎症级联反应,超过参考血管紧张素受体阻滞剂;即氯沙坦。
OBJECTIVE: While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed to assess the renoprotective potentials of methanol (MO) and methylene chloride (MC) fixed oil extracts of purslane seeds in a diabetic nephropathy (DN) model.
METHODS: Purslane seeds were extracted using absolute methanol and methylene chloride, and type-1 diabetes was induced with a single 55 mg/kg dose of Streptozotocin (STZ) dissolved in 100 mmol/L citrate buffer (pH 4.5), and then diabetic animals were received MO, MC, for 42 consecutive days to compare their antidiabetic effect relative to the reference drug \"Losartan\". Renal functions and DN biomarkers were weekly assessed, and the relative expression of different oxido-inflammatory mediators was quantified in diabetic kidneys by RT-PCR. Data were statistically analyzed using GraphPad Prism 9.0.2.
RESULTS: The oral administration of MO and MC extracts (250 mg/kg/day) significantly ameliorated the body weight loss (P < 0.0001 / each), fasting blood glucose levels (FBG) (P < 0.0001 / each), urine volume (P < 0.0001 / each), as well as serum creatinine (P < 0.0001 / each), uric acid (P = 0.0022, 0.0052), and blood urea nitrogen (BUN) (P = 0.0265, 0.0338); respectively, compared with the untreated diabetic rats. In addition, both extracts restored the effectuality of antioxidative machinery in diabetic kidneys as indicated by a significant reduction of ROS accumulation and lipid peroxidation; higher GSH content, and promoted activity of glutathione reductase and superoxide dismutase antioxidant enzymes (P < 0.0001 / each). Histologically, both extracts alleviated the DN-structural alterations including the glomerular congestion and tubular degeneration, with MC-treated kidneys showing near to normal architecture. The transcription profiles of all treated kidneys revealed a significantly downregulated expression of TNF-α, IL-6, Keap1 and NF-κB genes, concomitant with a significant upregulation of SDF-1, IL-10, Nrf2, HO-1, and
PPARγ gene expression (P < 0.0001 / all).
CONCLUSIONS: These findings highlight the remarkable DN-prophylactic potentials of purslane extracts mediated by neutralizing the hyperglycemia-induced ROS accumulation, and circumventing the downstream inflammatory cascades, surpassing the reference angiotensin receptor blocker; i.e. Losartan.