Department of Pharmacology/Toxicology, University of Louisville , Louisville, Kentucky.
College of Pharmacology/Toxicology, University of Arizona , Tucson, Arizona.
Am J Physiol Renal Physiol. 2019 Jan 1;316(1):F162-F172. doi: 10.1152/ajprenal.00463.2018. Epub 2018 Nov 28.
Aging is a risk factor for certain forms of kidney injury due to normal physiological changes, but the role of aging in cisplatin-induced kidney injury is not well defined in humans or animal models of the disease. To improve on current knowledge in this field, we treated 8- and 40-wk-old FVB/n mice with one high dose of cisplatin as a model of acute kidney injury or with repeated low doses of cisplatin (7 mg/kg cisplatin once a week for 4 wk) as a clinically relevant model of chronic kidney disease to determine if aging exacerbates cisplatin-induced kidney injury. Levels of acute kidney injury were comparable in 8- and 40-wk-old mice. In 40-wk-old mice, fibrotic markers were elevated basally, but treatment with cisplatin did not exacerbate fibrosis. We concluded that this may be the result of a decreased inflammatory response in 40-wk-old cisplatin-treated mice compared with 8-wk-old mice. Despite a decreased inflammatory response, the level of immune cell infiltration was greater in 40-wk-old cisplatin-treated mice than 8-wk-old mice. Our data highlight the importance of examining age as a risk factor for cisplatin-induced kidney injury.
衰老是导致某些类型肾脏损伤的一个风险因素，这是由于正常的生理变化所致，但衰老在人类或疾病动物模型的顺铂诱导的肾脏损伤中的作用尚未得到明确界定。为了改进该领域的现有知识，我们用单次高剂量顺铂（作为急性肾损伤模型）或重复低剂量顺铂（每周 7mg/kg 顺铂，连续 4 周）治疗 8 周和 40 周龄的 FVB/n 小鼠（作为慢性肾脏病的临床相关模型），以确定衰老是否会加重顺铂诱导的肾脏损伤。8 周和 40 周龄小鼠的急性肾损伤水平相当。在 40 周龄小鼠中，纤维化标志物基础水平升高，但顺铂治疗并未加剧纤维化。我们得出结论，这可能是由于与 8 周龄小鼠相比，40 周龄顺铂处理小鼠的炎症反应减弱所致。尽管炎症反应减弱，但 40 周龄顺铂处理小鼠的免疫细胞浸润水平高于 8 周龄小鼠。我们的数据强调了将年龄作为顺铂诱导的肾脏损伤的风险因素进行检查的重要性。
