【摘要】 目的 基于白细胞介素-1β(IL-1β）/核因子-κB(NF-κB）通路探讨四妙丸（SMW）抑制高尿酸血症（HUA）大鼠肠道炎症反应、促进尿酸肠道排泄的机制。方法 将 40 只 SD 大鼠随机分为空白对照（CON）组、模型（MOD）组、SMW 组、依托考昔（ETO）组和吡咯烷二硫代甲酸铵（PDTC）组（n=8）。除 CON 组外，其余各组大鼠予以氧嗪酸钾 100 mg/（kg·d）腹腔注射联合次黄嘌呤 500 mg/（kg·d）灌胃处理建立 HUA 模型。从造模后第 8 天起，MOD 组灌胃给予 10 mL/（kg·d）氯化钠溶液（9 g/L),SMW组灌胃给予 1 130.3 mg/（kg·d) SMW,ETO 组灌胃给予 5.4 mg/（kg·d) ETO,PDTC 组灌胃给予 100 mg/（kg·d) PDTC。连续干预14 d后，全自动生化分析仪分析大鼠血尿酸变化；苏木精-伊红（HE）染色检测肠道组织病理变化；酶联免疫吸附试验（ELISA）检测血清 IL-1β；聚合酶链式反应（PCR）法检测大鼠回肠 IL-1β、NF-κB p65 及 ATP 结合盒亚家族 G 成员 2(ABCG2）的 mRNA 表达水平；Western blot 法检测大鼠回肠 IL-1β、NF-κB p65、磷酸化 NF-κB p65(p-NF-κB p65）及 ABCG2 的蛋白表达水平；免疫组织化学染色（IHC）法检测大鼠回肠 ABCG2 蛋白表达水平。结果 (1)HUA 大鼠模型成功建立，表现为血清尿酸水平显著增加（P<0.05);SMW、ETO 及 PDTC能显著降低 HUA大鼠血清尿酸水平（P<0.05）。(2)SMW 能显著减少 HUA大鼠回肠绒毛破坏、减轻细胞脱落及降低中性粒细胞浸润；ETO 和 PDTC 能减少 HUA 大鼠回肠绒毛的破坏、减轻细胞脱落及降低中性粒细胞浸润，但改善效果不明显。(3)SMW、ETO 和 PDTC 能显著降低 HUA 大鼠血清中 IL-1β 水平（P<0.05）。(4)SMW 和 ETO 能显著降低大鼠回肠 IL-1β 和 NF-κB p65 的蛋白及 mRNA 表达（P<0.05);PDTC 能显著降低大鼠回肠 IL-1β 和 NF-κB p65 的蛋白表达（P<0.05）。(5)SMW能显著增加ABCG2的蛋白及mRNA表达（P<0.05），而ETO及PDTC只能增加ABCG2蛋白表达（P<0.05），且效果不如SMW。结论 SMW能有效降低血尿酸而改善HUA，其机制可能是通过抑制回肠IL-1β/NF-κB通路上调回肠ABCG2表达。更多还原

【Abstract】 Objective To investigate the mechanism of Simiao Pill (SMW) inhibiting intestinal inflammation and promoting the intestinal excretion of uric acid in hyperuricemia (HUA) rats based on the interleukin-1β (IL-1β）/nuclear factor-κB (NF-κB) pathway.Methods Forty SD rats were randomly divided into blank control (CON) group,model (MOD) group,SMW group,etoricoxib (ETO) group,and pyrrolidinedithiocarbamate ammonium (PDTC) group (n=8).Except CON group,rats in other groups were given intraperitoneal injection of potassium oxazinate at 100 mg/（kg·d) and intragastric administration of hypoxanthine at 500 mg/（kg·d) to establish HUA model.From the eighth day after modeling,MOD group was given 10 mL/（kg·d) sodium chloride solution (9 g/L) by gavage,SMW group was given 1 130.3 mg/（kg·d) SMW by gavage,ETO group was given 5.4 mg/（kg·d) ETO by gavage,and PDTC group was given 100mg/（kg·d) PDTC by intragastric administration.After 14 d of continuous intervention,serum uric acid levels were detected using an automatic biochemistry analyzer.Intestinal histopathology was examined using hematoxylin and eosin (HE) staining.Serum IL-1βlevels were measured using enzyme-linked immunosorbent assay(ELISA).The mRNA expressions of IL-1β,NF-κB p65,and ABCG2in the rat ileum were assessed by polymerase chain reaction (PCR).The protein expressions of IL-1β,NF-κB p65,phosphorylated NF-κB p65 (p-NF-κB p65),and ABCG2 in the rat ileum were analyzed by Western blot.The protein expression of ABCG2 in the rat ileum was evaluated by immunohistochemical (IHC) staining.Results (1) HUA rat model was established successfully,characterized by a significant increase in serum uric acid levels (P<0.05).SMW,ETO,and PDTC could significantly reduce serum uric acid levels in HUA rats.(2) SMW could significantly reduce the damage to the intestinal villi,alleviate cell shedding,and decrease neutrophil infiltration in the ileum of HUA rats.ETO and PDTC could reduce the damage to the ileal villi,alleviate the cell shedding,and decrease the neutrophil infiltration,but the improvement effect was not obvious.(3) SMW,ETO,and PDTC could significantly reduce the serum IL-1β levels in HUA rats (P<0.05).(4) SMW and ETO could significantly reduce the protein and mRNA expressions of IL-1β and NF-κB p65 in the ileum of the rats (P<0.05);And PDTC could significantly reduce the protein expression of IL-1β and NF-κB p65 in the ileum (P<0.05).(5) SMW could significantly increase the protein and mRNA expressions of ABCG2 (P<0.05).However,ETO and PDTC could only increase the ABCG2 protein expression (P<0.05),and the effect was worse than that of SMW.Conclusions SMW can effectively reduce the serum uric acid level and improve HUA.The mechanism may involve up-regulating ABCG2 expression by inhibiting the IL-1β/NF-κB pathway in the ileum.更多还原