School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.
Department of Internal Medicine, Liaoning Provincial Corps Hospital of Chinese People's Armed Police Forces, Shenyang, China.
Aging (Albany NY). 2022 Oct 20;14(20):8302-8320. doi: 10.18632/aging.204304.
Obesity enhances the frequency and severity of acute kidney injury (AKI) induced by renal ischemia-reperfusion (IR). Tanshinone IIA (TIIA) pre-treatment was used to alleviate renal injury induced by renal IR, and whether TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats was examined.
Male rates were fed a high-fat diet for 8 weeks to generate obesity, followed by 30 min of kidney ischemia and 24 h reperfusion induced AKI. The male obese rates were given TIIA (5 mg/kg.d, 10 mg/kg.d, and 20 mg/kg.d) for 2 weeks before renal IR.
TIIA alleviated the pathohistological injury and apoptosis induced by IR. In addition, TIIA improved renal function, inflammatory factor, and balance of oxidation and antioxidation in obese rats after renal IR. At the same time, TIIA can inhibit cell apoptosis by improving mitochondrial function through the PI3K/Akt/Bad pathway. Mitochondrial dysfunction was supported by decreasing intracellular ATP, respiration controlling rate (RCR), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex enzymes, and by increasing ROS, the opening of mitochondrial permeability transition pore (mPTP), and the mtDNA damage. The injury to mitochondrial dynamic function was assessed by decreasing Drp1, and increasing Mfn1/2; and the injury of mitochondrial biogenesis was assessed by decreasing PGC-1, Nrf1, and TFam.
Renal mitochondrial dysfunction occurs along with renal IR and can induce renal cell apoptosis. Obesity can aggravate apoptosis. TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats.
肥胖增强了肾缺血再灌注（IR）引起的急性肾损伤（AKI）的频率和严重程度。丹参酮 IIA（TIIA）预处理用于减轻肾 IR 引起的肾损伤，并且检查 TIIA 是否可以通过调节 PI3K/Akt/Bad 通路来调节线粒体功能从而减轻肥胖大鼠的肾细胞凋亡。
雄性大鼠喂食高脂肪饮食 8 周以产生肥胖，然后进行 30 分钟的肾缺血和 24 小时的再灌注以诱导 AKI。在肾 IR 之前，雄性肥胖大鼠给予 TIIA（5mg/kg.d、10mg/kg.d 和 20mg/kg.d）2 周。
TIIA 减轻了 IR 引起的病理组织学损伤和细胞凋亡。此外，TIIA 改善了肥胖大鼠肾 IR 后的肾功能、炎症因子和氧化与抗氧化平衡。同时，TIIA 通过 PI3K/Akt/Bad 通路改善线粒体功能来抑制细胞凋亡。线粒体功能障碍通过降低细胞内 ATP、呼吸控制率（RCR）、线粒体膜电位（MMP）和线粒体呼吸链复合物酶，增加 ROS、线粒体通透性转换孔（mPTP）的开放以及 mtDNA 损伤来支持。通过降低 Drp1 和增加 Mfn1/2 来评估线粒体动态功能的损伤；通过降低 PGC-1、Nrf1 和 TFam 来评估线粒体生物发生的损伤。
肾线粒体功能障碍与肾 IR 一起发生，并可诱导肾细胞凋亡。肥胖可以加重细胞凋亡。TIIA 可以通过调节 PI3K/Akt/Bad 通路来调节线粒体功能，从而减轻肥胖大鼠的肾细胞凋亡。
