School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, P.R. China.
Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, 264000, Yantai, Shandong P.R. China.
Phytother Res. 2018 Jan;32(1):103-114. doi: 10.1002/ptr.5954. Epub 2017 Oct 26.
Renal ischaemia-reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Peritubular capillary (PTC) endothelium damages are an important pathogenesis during I/R AKI. Salvianolic acid A (SAA) possesses various pharmacological activities. The study investigated whether SAA ameliorated I/R AKI through protecting against PTC endothelium damages. Male Sprague-Dawley rats were divided into 6 groups: control, sham, I/R, and I/R plus SAA (2.5, 5, 10 mg/kg) groups. Rats were subjected to bilateral renal pedicle clamping for 60 min, and killed at 24 hr after reperfusion. Kidney injury, PTC endothelium damages and factors affecting PTC endothelium were evaluated. SAA significantly decreased blood urea nitrogen and serum creatinine levels, and reduced urine kidney injury molecule-1 concentration. Simultaneously, SAA alleviated histological damages, prevented PTC endothelium damages, preserved the density of PTC and improved renal hypoxia. Furthermore, SAA inhibited platelet activation, elevated Klotho protein expression and up-regulated vascular endothelial growth factor A expression. Overall, SAA has protective effects on AKI induced by I/R. Preventing PTC endothelium damages and preserving PTC integrity to improve the renal hypoxia may be the ways for SAA to ameliorate AKI. All these indicate that SAA is likely to be a promising agent for AKI.
肾缺血再灌注（I/R）损伤是急性肾损伤（AKI）最常见的原因。肾小管周毛细血管（PTC）内皮损伤是 I/R 性 AKI 的重要发病机制之一。丹酚酸 A（SAA）具有多种药理活性。本研究旨在探讨 SAA 是否通过保护 PTC 内皮来改善 I/R 性 AKI。雄性 Sprague-Dawley 大鼠分为 6 组：对照组、假手术组、I/R 组和 I/R 加 SAA（2.5、5、10mg/kg）组。大鼠双侧肾蒂夹闭 60min，再灌注 24h 后处死。评估肾脏损伤、PTC 内皮损伤和影响 PTC 内皮的因素。SAA 显著降低血尿素氮和血清肌酐水平，减少尿肾损伤分子-1 浓度。同时，SAA 减轻组织学损伤，防止 PTC 内皮损伤，维持 PTC 密度，改善肾缺氧。此外，SAA 抑制血小板活化，提高 Klotho 蛋白表达，上调血管内皮生长因子 A 表达。总之，SAA 对 I/R 诱导的 AKI 具有保护作用。防止 PTC 内皮损伤和维持 PTC 完整性以改善肾缺氧可能是 SAA 改善 AKI 的途径。所有这些都表明 SAA 可能是 AKI 的一种有前途的治疗药物。
