Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway

Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250–300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

丹酚酸B（Salvianolic acid B，SAB）是丹参（Radix Salvia miltiorrhiza）的主要植物活性成分之一，具备多种有益于机体健康的生理活性。本研究旨在探讨SAB是否可通过激活磷脂酰肌醇3-激酶/丝氨酸-苏氨酸激酶B（PI3K/Akt）信号通路，减轻肾缺血再灌注大鼠模型中的氧化应激与炎症反应，从而发挥肾保护作用。

本实验选取40只体质量250~300 g的雄性Sprague-Dawley（SD）大鼠，随机分为4组，每组10只。所有大鼠均行右侧肾摘除术（肾切除术）。对照组仅给予生理盐水处理（仅行左侧肾动脉夹闭操作），作为假手术对照组；仅通过夹闭左侧肾动脉构建缺血再灌注（ischemic reperfusion, IR）损伤模型的大鼠作为阳性对照组。剩余2组大鼠在IR造模前7天分别给予20 mg·kg⁻¹·d⁻¹和40 mg·kg⁻¹·d⁻¹的SAB预处理，作为治疗组（分别记为SAB 20+IR组、SAB 40+IR组）。

检测结果显示，SAB干预组的肾损伤标志物肌酐（creatinine, Cr）与血尿素氮（blood urea nitrogen, BUN）水平显著降低。SAB预处理可通过抑制丙二醛（malondialdehyde）等脂质过氧化产物的生成、提升抗氧化活性，从而缓解氧化应激。同时，炎症标志物水平与反映中性粒细胞浸润的髓过氧化物酶（myeloperoxidase）活性均显著下降。此外，SAB给药可显著上调PI3K蛋白表达及pAkt/Akt比值，证实其具备肾保护活性。

综上，本研究结果表明，SAB可通过调控PI3K/Akt信号通路，有效减轻氧化应激与炎症反应进程，进而改善肾功能，有望成为新型肾保护剂。