Xijing Hospital, Medical University of the Air Force, Department of Pharmacy, Xi'an, Shaanxi, 710032, China.
Shaanxi University of Chinese Medicine, Department of Pharmacy, Xianyang, shaanxi, 712046, China.
Sci Rep. 2018 Jun 15;8(1):9173. doi: 10.1038/s41598-018-27217-3.
This study aimed to evaluate the protective effect of hydroxysafflor yellow A (HSYA) on ischemia/reperfusion (I/R)-induced acute kidney injury via the TLR4/NF-κB pathway, both in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney. Rats subjected to renal I/R injury were treated with HSYA at 0.5 h prior to I/R injury. Renal function, histopathological analysis, and cells apoptosis were measured in vivo. In vitro, proximal renal tubular cells (HK-2) were subjected to hypoxia/reoxygenation (H/R). Apoptotic cell death and inflammatory cytokines, Toll-like receptor 4 (TLR4), and nuclear factor (NF)-κB expression were determined. Treatment of I/R rats with HSYA markedly reduced the levels of serum creatinine and blood urea nitrogen, attenuated renal cell apoptosis, alleviated changes in renal tissue morphology, and reduced IL-1β, TNF-α, and caspase-3 release. In vitro, HSYA effectively decreased NF-κB p65 and inflammatory cytokines, such as IL-1β, TNF-α, and IL-6. Thus, HSYA can protect renal function from I/R injury by ameliorating acute kidney injury and partly by promoting tubular cell survival via the TLR4/NF-κB pathway. These results suggest that HSYA can be used to prevent I/R-induced acute kidney injury.
本研究旨在通过 TLR4/NF-κB 通路,在体内和体外评估羟基红花黄色素 A (HSYA) 对缺血/再灌注 (I/R) 诱导的急性肾损伤的保护作用。大鼠被切除右肾并对左肾进行 I/R 损伤。在 I/R 损伤前 0.5h 用 HSYA 对接受肾 I/R 损伤的大鼠进行治疗。在体内测量肾功能、组织病理学分析和细胞凋亡。在体外,将近端肾小管细胞 (HK-2) 置于缺氧/复氧 (H/R) 下。测定凋亡细胞死亡和炎症细胞因子、Toll 样受体 4 (TLR4) 和核因子 (NF)-κB 的表达。用 HSYA 治疗 I/R 大鼠可显著降低血清肌酐和血尿素氮水平,减轻肾细胞凋亡,减轻肾组织形态变化,并减少白细胞介素-1β、肿瘤坏死因子-α 和半胱氨酸天冬氨酸蛋白酶-3 的释放。在体外,HSYA 能有效降低 NF-κB p65 和炎症细胞因子,如白细胞介素-1β、肿瘤坏死因子-α 和白细胞介素-6。因此,HSYA 通过改善急性肾损伤和部分通过 TLR4/NF-κB 通路促进管状细胞存活来保护肾功能免受 I/R 损伤。这些结果表明 HSYA 可用于预防 I/R 诱导的急性肾损伤。