Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; TCM institute of kidney disease, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Biomed Pharmacother. 2019 Oct;118:109316. doi: 10.1016/j.biopha.2019.109316. Epub 2019 Aug 3.
Apoptosis is closely interconnected with the severity of renal injury. Magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix showed a wide range of renoprotective effects. However, the underlying mechanisms under beneficial effects have not been elucidated. This study was conducted to investigate whether MLB could mediate renal protection and attenuate apoptosis by mitochondrial pathway. In the present study, the rat model of chronic renal failure (CRF) was established by the 5/6 renal ablation/infarction (A/I) operation. 28 days after the surgery, 30 rats were randomly divided into three groups: sham group, 5/6 (A/I) group and 5/6 (A/I) + MLB group. After 56 days of treatment, we detected the severity of kidney injury, the degree of mitochondrial bax oligomerization and cytochrome c release along with the expression of P53 protein. Our results showed that MLB markedly attenuated kidney injury and apoptosis in 5/6 (A/I) model rats with CRF. MLB effectively inhibited mitochondrial bax accumulation and release of cytochrome c into the cytosol and down-regulated the levels of p53 phosphorylation and acetylation. These data showed that MLB could contribute to renal protection by inhibiting mitochondrial pathway of apoptosis.
细胞凋亡与肾损伤的严重程度密切相关。丹参中的丹参素 B(MLB)具有广泛的肾保护作用。然而,其有益作用的潜在机制尚未阐明。本研究旨在探讨 MLB 是否可以通过线粒体途径介导肾脏保护和减轻细胞凋亡。在本研究中,通过 5/6 肾切除/梗死(A/I)手术建立大鼠慢性肾衰竭(CRF)模型。手术后 28 天,将 30 只大鼠随机分为三组:假手术组、5/6(A/I)组和 5/6(A/I)+MLB 组。治疗 56 天后,我们检测了肾脏损伤的严重程度、线粒体 bax 寡聚化和细胞色素 c 释放的程度以及 P53 蛋白的表达。结果表明,MLB 可显著减轻 CRF 5/6(A/I)模型大鼠的肾脏损伤和细胞凋亡。MLB 可有效抑制线粒体 bax 的积累和细胞色素 c 向细胞质的释放,并下调磷酸化和乙酰化 p53 的水平。这些数据表明,MLB 可以通过抑制细胞凋亡的线粒体途径来促进肾脏保护。