The polyamine system in gender-related renoprotection (B05)

我们将研究多胺系统的变化如何导致AKI的性别依赖性易感性。为了了解与性别相关的多胺水平对AKI结果的影响，我们将雄性小鼠和未切除性腺的雌性小鼠以及接受和未接受睾丸激素治疗的雌性小鼠暴露于肾脏IRI中。这些动物的多胺生成和分解将被阻断，以探索是否可以通过药物抑制多胺系统来减弱AKI结果的性别依赖性差异。此外，小鼠胚胎肾移植体和斑马鱼幼体将被用作筛选工具，以研究睾酮如何干扰靶向多胺体内平衡以保护肾的前瞻性药物。

We will investigate how changes in the polyamine system contribute to the gender-dependent susceptibility to AKI. To recognize the influence of sex-related polyamine levels on the outcome of AKI, we will expose male mice with and without gonadectomy and female mice with and without testosterone treatment to renal IRI. Polyamine production and breakdown in these animals will be blocked to explore whether gender-dependent differences in the outcome of AKI can be attenuated by pharmacologic inhibition of the polyamine system. Furthermore, murine embryonic kidney explants and zebrafish larvae will be used as screening tools to investigate how testosterone interferes with prospective drugs targeting the homeostasis of polyamines for renoprotection.