高尿酸血症小鼠模型的构建及其免疫稳态的变化

Construction of hyperuricemia mice model and changes of immune homeostasis

高尿酸血症发病率逐年增高,高尿酸对机体健康的影响已成为生物医药领域的热点和前沿问题。现有研究证实,高尿酸水平对患者关节和肾脏造成慢性损伤,但对免疫稳态影响的研究较少。通过不同化学诱导剂成功构建了3种高尿酸血症小鼠模型,并对其尿酸变化、肾脏病理改变以及外周血中主要负责体液免疫的B细胞、负责细胞免疫的T细胞以及先天性免疫细胞NK细胞等免疫细胞比例进行了详细研究。结果显示,相比正常对照组,3种高尿酸血症小鼠模型的B细胞比例均出现显著下降,且600 mg/kg高剂量黄嘌呤暴露组的CD4^(+)T细胞、CD8^(+)T细胞以及B细胞下降尤为显著。本研究从免疫稳态角度揭示了高尿酸血症对机体的重要影响,为高尿酸血症模型的构建提供了参考,为高尿酸血症诱发痛风等疾病的发病机制提供了新的思路。

The incidence of hyperuricemia is increasing year by year,and the impact of hyperuricemia on human health has become a hot and cutting-edge issue in the field of biomedicine.Existing studies have confirmed that long-term high uric acid levels can cause chronic damage to patients′joints and kidneys,but there are still few studies on the impact on immune homeostasis.This study successfully constructed three mouse models of hyperuricemia using different chemical inducers,and analyzed changes in uric acid,renal pathological changes,B cells in peripheral blood that are mainly responsible for humoral immunity,T cells that are responsible for cellular immunity,and innate proportion of immune cells such as NK cells and other immune cells was studied in detail.The results showed that compared with the normal control group,the proportion of B cells in the three hyperuricemia mouse models all decreased significantly,and the proportion of CD4^(+)T cells,CD8^(+)T cells and B cells in the 600 mg/kg high-dose xanthine exposure group declined particularly significant.This study reveals the important impact of hyperuricemia on the body from the perspective of immune homeostasis,provides a reference for the construction of a hyperuricemia model,and puts forward new ideas for the pathogenesis of gout and other diseases induced by hyperuricemia.