基于NLRP3炎症信号通路探讨山核桃叶总黄酮抗高尿酸血症作用机制研究

Action mechanism of total flavoniods from Carya cathayensis leaves in therapy of hyperuricemia based on NLRP3 inflammasomes signaling pathway

目的探讨山核桃叶总黄酮对高尿酸血症模型小鼠NLRP3炎性信号表达的影响。方法 ICR雄鼠腹腔注射氧嗪酸钾建立高尿酸血症动物模型,并将造模成功后的小鼠按体质量随机分为6组,每组8只,分别为模型组、Caspase-1抑制剂组、苯溴马隆组、山核桃叶总黄酮低剂量、中剂量、高剂量(50 mg/kg、100 mg/kg、200 mg/kg)组,另设正常组。用ELISA法检测各组血清IL-1β前体、IL-1β、IL-18炎性因子水平;Western blot检测肾脏组织NLRP3、Caspase-1、ASC表达情况。结果与正常组比较,模型组NLRP3、Caspase-1、ASC、IL-1β前体、IL-1β、IL-18表达显著升高(P<0.05);与模型组比较,山核桃叶总黄酮高剂量组IL-1β和IL-18的水平显著降低(P<0.01),肾脏组织NLRP3、Caspase-1、ASC蛋白相对表达量均显著降低(P<0.01)。结论山核桃叶总黄酮可通过干预高尿酸血症模型小鼠体内NLRP3信号的传导,降低炎性因子的表达,减轻炎症反应。

Objective To study the effect of total flavoniods from Carya cathayensis leaves on NLRP3 inflammatory signal expression in hyperuricemia mice models.Methods ICR male hyperuricemia mice models were constructed by intraperitoneal injection of oteracil potassium,and 56 mice were randomly divided into normal control group,model group,Caspase-1 inhibitor group,benzbromarone group,total flavoniods from Carya cathayensis leaves low-dose group,medium-dose group,and high-dose group(respectively 50 mg/kg,100 mg/kg,200 mg/kg),with 8 cases in each group.The levels of pro-IL-1β,IL-1β,IL-18 were detected by ELISA,while the protein expressions of NLRP3,Caspase-1 and ASC in kidney tissue were detected by Western blot.Results Compared with control group,the expressions of NLRP3,ASC,pro-IL-1β,IL-1β,IL-18 in model group were upregulated(P<0.05).Compared with model group,the levels of IL-1β,IL-18,and the protein levels of NLRP3,Caspase-1 besides ASC in total flavoniods high-dose group significantly decreased(P<0.01).Conclusion Total flavoniods from Carya cathayensis leaves could intervene hyperuricemia mice in NLRP3 inflammasomes signaling pathway,which may reduce the expression of interleukin and the reaction of inflammation.