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牛磺酸通过 p38MAPK 和 TGF-β/Smad2/3 信号通路对糖尿病肾病的肾保护作用。

The renoprotective effects of taurine against diabetic nephropathy via the p38 MAPK and TGF-β/Smad2/3 signaling pathways.

机构信息

Department of Molecular Medicine, Health Sciences Institute, Dokuz Eylul University, 35340, Izmir, Turkey.

Multidisciplinary Experimental Animal Laboratory, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.

出版信息

Amino Acids. 2023 Nov;55(11):1665-1677. doi: 10.1007/s00726-023-03342-w. Epub 2023 Oct 7.

Abstract

Diabetic nephropathy (DN), a severe diabetes complication, causes kidney morphological and structural changes due to extracellular matrix accumulation. This accumulation is caused mainly by oxidative stress. Semi-essential amino acid derivative taurine has powerful antioxidant and antifibrotic effects. The aim of this study was to investigate the renoprotective effects of taurine through its possible roles in oxidative stress, extracellular matrix proteins, and the signaling pathways associated with the accumulation of extracellular matrix proteins in DN rats. 29 Wistar albino rats were randomly separated into control, taurine, diabetes, and diabetes + taurine groups. Diabetes animals were injected 45 mg/kg streptozosine. Taurine is given by adding to drinking water as 1% (w/v). Urine, serum, and kidney tissue were collected from rats for biochemical and histological analysis after 12 weeks. According to the studies, taurine significantly reduces the levels of malondialdehyde (MDA), total oxidant status (TOS), and protein expression of NADPH oxidase 4 (NOX4) that increase in diabetic kidney tissue. Also, decreased superoxide dismutase (SOD) activity levels significantly increased with taurine in diabetic rats. Moreover, increased mRNA and protein levels of fibronectin decreased with taurine. The matrix metalloproteinase (MMP)-2 and MMP-9 activities and their mRNA levels increased significantly, and this increase was significantly summed with taurine. There was a decrease in mRNA expression of Extracellular matrix metalloproteinase inducer (EMMPRIN). Taurine significantly increased this decrease. Diabetes increased mRNA expressions of transforming growth factor (TGF)-β and Smad2/3. Taurine significantly reduced this induction. TGF-β protein expression, p38, and Smad2/3 activations were also inhibited, but taurine was suppressed significantly. All these findings indicate that taurine may be an effective practical strategy to prevent renal diabetic injury.

摘要

糖尿病肾病(DN)是一种严重的糖尿病并发症,由于细胞外基质的积累,导致肾脏形态和结构发生变化。这种积累主要是由氧化应激引起的。半必需氨基酸衍生物牛磺酸具有强大的抗氧化和抗纤维化作用。本研究旨在通过牛磺酸在氧化应激、细胞外基质蛋白以及与细胞外基质蛋白积累相关的信号通路中的可能作用,研究牛磺酸的肾保护作用。29 只 Wistar 白化大鼠随机分为对照组、牛磺酸组、糖尿病组和糖尿病+牛磺酸组。糖尿病动物注射 45mg/kg 链脲佐菌素。牛磺酸通过添加到饮用水中作为 1%(w/v)给予。12 周后从大鼠中收集尿液、血清和肾脏组织进行生化和组织学分析。根据研究,牛磺酸可显著降低糖尿病肾脏组织中增加的丙二醛(MDA)、总氧化剂状态(TOS)和 NADPH 氧化酶 4(NOX4)的蛋白表达。此外,糖尿病大鼠中 SOD 活性水平的显著降低也随牛磺酸而增加。此外,纤连蛋白的 mRNA 和蛋白水平降低,牛磺酸也随之降低。基质金属蛋白酶(MMP)-2 和 MMP-9 的活性及其 mRNA 水平显著增加,与牛磺酸一起显著增加。细胞外基质金属蛋白酶诱导因子(EMMPRIN)的 mRNA 表达减少。牛磺酸显著增加了这种减少。糖尿病大鼠转化生长因子(TGF)-β和 Smad2/3 的 mRNA 表达增加。牛磺酸显著降低了这种诱导作用。TGF-β 蛋白表达、p38 和 Smad2/3 的激活也受到抑制,但牛磺酸的抑制作用显著。所有这些发现表明,牛磺酸可能是预防肾脏糖尿病损伤的有效实用策略。

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