School of Chemistry and Chemical Engineering, Xianyang Normal University, No.43 Wenlin Road, Xianyang 712000, Shaanxi, China.
Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.
Pharmacol Ther. 2022 Sep;237:108169. doi: 10.1016/j.pharmthera.2022.108169. Epub 2022 Mar 17.
Acute kidney injury (AKI) is a sudden loss of kidney function that causes a rise in serum creatinine and a decrease in urine output, which leads to high morbidity and mortality. However, effective therapeutic drugs have not yet been developed due to the poor understanding of the cellular and molecular mechanisms of AKI. Recent studies have revealed that AKI leads to renal disorders, including inflammation, cell apoptosis, oxidative stress, mitochondrial dysfunction and autophagy, and multiple signaling pathways are involved in these disorders during the pathogenesis of AKI, which suggests that drugs specifically targeting these signaling pathways may be effective in preventing and treating AKI. In addition, a great number of small molecules show a therapeutic effect on AKI by targeting these signaling pathways and may be promising therapeutic drugs in the treatment of AKI. Moreover, an in-depth analysis of failed clinical trials is carried out to find out an effective strategy for AKI therapy. Taken together, this review focuses on the cellular and molecular mechanisms of AKI and the small molecules that alleviate AKI, which will provide new insight into AKI therapy.
急性肾损伤(AKI)是一种肾脏功能突然丧失的疾病,会导致血清肌酐升高和尿量减少,从而导致高发病率和死亡率。然而,由于对 AKI 的细胞和分子机制的了解不足,尚未开发出有效的治疗药物。最近的研究表明,AKI 导致肾脏紊乱,包括炎症、细胞凋亡、氧化应激、线粒体功能障碍和自噬,并且在 AKI 的发病机制中,多个信号通路参与了这些紊乱,这表明针对这些信号通路的药物可能在预防和治疗 AKI 方面有效。此外,大量的小分子通过靶向这些信号通路对 AKI 显示出治疗效果,可能是治疗 AKI 的有前途的治疗药物。此外,对失败的临床试验进行深入分析,以找到 AKI 治疗的有效策略。总之,本综述重点介绍 AKI 的细胞和分子机制以及减轻 AKI 的小分子,这将为 AKI 治疗提供新的见解。