Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Shanghai Institute of Kidney Disease and Dialysis (SIKD), Shanghai, People's Republic of China.
Drug Des Devel Ther. 2022 Jul 15;16:2293-2304. doi: 10.2147/DDDT.S358830. eCollection 2022.
Apoptosis plays a critical role in cisplatin-induced acute kidney injury (AKI) and is related to mitochondrial dysfunction. Magnesium lithospermate B (Mlb), one of the most important components of Bunge, is mainly used to treat cardiovascular diseases because of its anti-apoptotic effects. The mechanism underlying the protective effect of Mlb against cisplatin-induced AKI remains unclear. In this study, we investigated the protective effect of Mlb on mitochondrial function against apoptosis caused by cisplatin-induced renal injury.
Renal injury induced by cisplatin in mouse renal tubular epithelial cells (mTECs) was measured by quantifying serum creatinine levels, mitochondrial morphology, cell viability, apoptosis, Dynamin-related protein 1(Drp1) expression, etc. The cells were then administered Mlb to determine its protective effects against cisplatin-induced AKI.
Mlb treatment significantly reduced serum creatinine levels and pathological injury of renal, inhibited the production of malondialdehyde, and reduced the depletion of superoxide dismutase. In addition, Mlb reduced Bax/Bcl2, cleaved caspase-3/caspase-3, and maintained mitochondrial integrity after AKI. Mlb administration also improved cell viability and reduced the percentage of apoptotic cells in vitro. Furthermore, Mlb reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential, and ameliorated mitochondrial morphological abnormalities by downregulating Drp1 expression.
These results indicated that Mlb could protect the kidneys against cisplatin-induced apoptosis by alleviating mitochondrial dysfunction.
细胞凋亡在顺铂诱导的急性肾损伤（AKI）中起关键作用，与线粒体功能障碍有关。虎杖中的主要成分之一镁 Lithospermate B（Mlb），由于其抗凋亡作用，主要用于治疗心血管疾病。Mlb 对顺铂诱导的 AKI 的保护作用的机制尚不清楚。在这项研究中，我们研究了Mlb 对线粒体功能的保护作用，以防止顺铂诱导的肾损伤引起的细胞凋亡。
通过定量测定血清肌酐水平、线粒体形态、细胞活力、细胞凋亡、Dynamin 相关蛋白 1（Drp1）表达等，检测顺铂诱导的小鼠肾小管上皮细胞（mTECs）中的肾损伤。然后给予细胞Mlb，以确定其对顺铂诱导的 AKI 的保护作用。
Mlb 治疗可显著降低血清肌酐水平和肾病理损伤，抑制丙二醛的产生，减少超氧化物歧化酶的耗竭。此外，Mlb 降低了 Bax/Bcl2、cleaved caspase-3/caspase-3 的比值，并在 AKI 后维持了线粒体的完整性。Mlb 给药还可提高细胞活力，减少体外凋亡细胞的百分比。此外，Mlb 通过下调 Drp1 表达，减少线粒体活性氧、改善线粒体膜电位和改善线粒体形态异常，从而保护肾脏免受顺铂诱导的凋亡。
这些结果表明，Mlb 可以通过减轻线粒体功能障碍来保护肾脏免受顺铂诱导的细胞凋亡。
