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染料木黄酮通过抑制 STZ 诱导的糖尿病大鼠肾组织中 TGF-β1 和 PAR-2 基因的表达,具有抗糖尿病、抗高血脂、抗氧化和对糖尿病肾病的保护作用。

Biochanin-A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF-β1 and PAR-2 genes expression in kidney tissues of STZ-induced diabetic rats.

机构信息

Traditional and Complementary Medicine Research Center, Department of Traditional medicine, School of Medicine, Arak University of Medical Sciences, Arak, Iran.

Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Biotechnol Appl Biochem. 2022 Oct;69(5):2112-2121. doi: 10.1002/bab.2272. Epub 2021 Oct 28.

Abstract

One of the major complications of diabetes is diabetic nephropathy, and often many patients suffer from diabetic nephropathy. That is why it is important to find the mechanisms that cause nephropathy and its treatment. This study was designed to examine the antidiabetic effects of biochanin A (BCA) and evaluate its effects on oxidative stress markers and the expression of transforming growth factor-β1 (TGF-β1) and protease-activated receptors-2 (PAR-2) genes in the kidney of type 1 diabetic rats. After induction of diabetes using streptozotocin (STZ), 55 mg/kg bw dose, rats were randomly divided into four groups with six rats in each group as follows: normal group: normal control receiving normal saline and a single dose of citrate buffer daily; diabetic control group: diabetic control receiving 0.5% dimethyl sulfoxide daily; diabetic+BCA (10 mg/kg) group: diabetic rats receiving biochanin A at a dose of 10 mg/kg bw daily; diabetic+BCA (15 mg/kg) group: diabetic rats receiving biochanin A at a dose of 15 mg/kg bw daily. TGF-β1 and PAR-2 gene expression was assessed by real-time. Spectrophotometric methods were used to measure biochemical factors: fast blood glucose (FBG), urea, creatinine, albumin, lipids profiles malondialdehyde (MDA), and superoxide dismutase (SOD). The course of treatment in this study was 42 days. The results showed that in the diabetic control group, FBG, serum urea, creatinine, expression of TGF-β1 and PAR-2 genes, and the levels of MDA in kidney tissue significantly increased and SOD activity in kidney tissue and serum albumin significantly decreased compared to the normal group (p < 0.001). The results showed that administration of biochanin A (10 and 15 mg/kg) after 42 days significantly reduced the expression of TGF-β1 and PAR-2 genes and FBG, urea, creatinine in serum compared to the diabetic control group (p < 0.001), also significantly increased serum albumin compared to the diabetic control group (p < 0.001). The level of MDA and SOD activity in the tissues of diabetic rats that used biochanin A (10 and 15 mg/kg) was significantly reduced and increased, respectively, compared to the diabetic control group (p < 0.001). Also, the result showed that in the diabetic control group lipids profiles significantly is disturbed compared to the normal group (p < 0.001), the results also showed that biochanin A (10 and 15 mg/kg) administration could significantly improved the lipids profile compared to the control diabetic group (p < 0.001). It is noteworthy that it was found that the beneficial effects of the biochanin A were dose dependent. In conclusion, administration of biochanin A for 42 days has beneficial effect and improves diabetes and nephropathy in diabetic rats. So probably biochanin A can be used as an adjunct therapy in the treatment of diabetes.

摘要

糖尿病的主要并发症之一是糖尿病肾病,许多患者经常患有糖尿病肾病。因此,找到导致肾病的机制及其治疗方法非常重要。本研究旨在研究生物黄酮 A(BCA)的抗糖尿病作用,并评估其对氧化应激标志物和转化生长因子-β1(TGF-β1)和蛋白酶激活受体-2(PAR-2)基因表达的影响。在使用链脲佐菌素(STZ)诱导糖尿病后,以 55mg/kg bw 的剂量,将 55 只大鼠随机分为四组,每组 6 只,如下所示:正常组:正常对照,给予生理盐水和柠檬酸缓冲液每日一次;糖尿病对照组:糖尿病对照,每日给予 0.5%二甲基亚砜;糖尿病+BCA(10mg/kg)组:糖尿病大鼠每日给予生物黄酮 A10mg/kg bw;糖尿病+BCA(15mg/kg)组:糖尿病大鼠每日给予生物黄酮 A15mg/kg bw。通过实时荧光定量 PCR 评估 TGF-β1 和 PAR-2 基因的表达。分光光度法用于测量生化因子:快速血糖(FBG)、尿素、肌酐、白蛋白、丙二醛(MDA)和超氧化物歧化酶(SOD)的脂质谱。在这项研究中,治疗过程持续 42 天。结果表明,与正常组相比,糖尿病对照组的 FBG、血清尿素、肌酐、TGF-β1 和 PAR-2 基因的表达以及肾脏组织中 MDA 的水平显著升高,而肾脏组织和血清白蛋白中的 SOD 活性显著降低(p<0.001)。结果表明,与糖尿病对照组相比,42 天后给予生物黄酮 A(10 和 15mg/kg)可显著降低 TGF-β1 和 PAR-2 基因和血清中的 FBG、尿素、肌酐(p<0.001),与糖尿病对照组相比,血清白蛋白水平也显著升高(p<0.001)。与糖尿病对照组相比,糖尿病大鼠组织中 MDA 水平和 SOD 活性分别显著降低和升高(p<0.001)。此外,结果表明,与正常组相比,糖尿病对照组的脂质谱显著紊乱(p<0.001),结果还表明,与糖尿病对照组相比,生物黄酮 A(10 和 15mg/kg)给药可显著改善脂质谱(p<0.001)。值得注意的是,研究发现生物黄酮 A 的有益作用呈剂量依赖性。总之,42 天给予生物黄酮 A 具有有益作用,可改善糖尿病大鼠的糖尿病和肾病。因此,生物黄酮 A 可能可作为糖尿病治疗的辅助治疗。

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