虫草素通过ALPK1-URAT1-NF-κB途径改善尿酸代谢机制研究

Since the hypouricemic effects of edible mushrooms were reported by us, its application for that was focused. However, the mechanism is not clear. In our previous study, it was found that cordycepin, a characteristic nutrient of Cordyceps militaris, alleviated uric acid metabolism in kidney through up-regulating ALPK1, down-regulating URAT1 and NF-κB in uric acid disorder mice. Therefore, we suggest that cordycepin alleviate uric acid metabolism in kidney by activating ALPK1-URAT1-NF-κB pathway. The present study intents to: (1) study the influences of cordycpin on the mRNA and protein expressions of the key genes of ALPK1-URAT1-NF-κB pathway and its downstream genes, such as IκBα、NF-κB、iNOS, utilizing integrated-omics technology; then (2) build cell models resembling uric acid disorder in NK-2 and THP1 cells by gene editing/chemical inhibiting and explore the regulation mechanism on ALPK1-URAT1-NF-kB pathway in the presence and absence of the stimulus cordycepin; (3) finally test the modulation on the pathway by cordycepin using gene knocked-out or specific inhibited mice. Our study would provide some understandings for the uric acid metabolism in kidney.

自我们报道食用菌具有改善尿酸代谢功能以来，其应用前景一直备受瞩目。然而，其具体调控机制亟需解答。我们前期研究发现：在尿酸代谢紊乱模型小鼠上，蛹虫草营养素虫草素上调肾脏ALPK1，下调URAT1和NF-κB，改善尿酸代谢。我们假设：虫草素通过激活肾脏ALPK1-URAT1-NF-κB途径改善尿酸代谢。据此，本项目拟开展：（1）以HUA动物模型为研究对象，整合组学技术，分析虫草素对肾脏ALPK1-URAT1-NF-κB及其上下游IκBα、iNOS等分子的调控作用；（2）采用基因编辑和/或化学抑制剂等方法，制备NK-2和THP1拟尿酸代谢紊乱细胞模型，使用虫草素刺激，系统分析虫草素调控ALPK1-URAT1-NF-κB的机制；（3）利用基因全身性敲除或特异性抑制小鼠，验证虫草素调控ALPK1-URAT1-NF-kB通路的作用。研究结果有助于认识尿酸在肾脏的代谢机制。

自我们报道食用菌具有改善尿酸代谢功能以来，其应用前景一直备受瞩目。然而，其具体调控机制亟需解答。我们前期研究发现：在尿酸代谢紊乱模型小鼠上，蛹虫草营养素虫草素上调肾脏ALPK1，下调URAT1和NF-κB，改善尿酸代谢。我们认为：虫草素通过激活肾脏ALPK1-URAT1-NF-κB途径改善尿酸代谢。据此，项目开展了：（1）以HUA动物模型为研究对象，整合组学技术，分析了虫草素对肾脏ALPK1-URAT1-NF-κB及其上下游IκBα、iNOS等分子的调控作用；（2）采用基因编辑和/或化学抑制剂等方法，制备NK-2和THP1拟尿酸代谢紊乱细胞模型，使用虫草素刺激，系统分析了虫草素调控ALPK1-URAT1-NF-κB的机制；（3）利用基因全身性敲除或特异性抑制小鼠，验证虫了草素调控ALPK1-URAT1-NF-kB通路的作用。研究结果为尿酸肾脏代谢机制提供了新认识。

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