四妙丸抑制IL-1β/NF-κB通路上调肠道ABCG2表达促进肠道尿酸排泄的机制  

Mechanism of Simiao Pill inhibiting IL-1β/NF-κB to up-regulate intestinal ABCG2 expression and promote uric acid excretion in intestine

作　　者：郝泽瀚 张远 张钟友 王凌椿 叶博闻 戴号 HAO Zehan;ZHANG Yuan;ZHANG Zhongyou;WANG Lingchun;YE Bowen;DAI Hao(Guanghua School of Clinical Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Orthopedic,Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200052,China)

机构地区：[1]上海中医药大学光华临床医学院,上海201203 [2]上海中医药大学附属光华医院骨科,上海200052

出　　处：《上海中医药杂志》2025年第3期77-84,共8页Shanghai Journal of Traditional Chinese Medicine

基　　金：上海市卫健委科研计划项目(202140164);上海市卫健委科研课题(20194Y0432);上海市长宁区医疗卫生科研专项基金(CNKW2020Y17);上海市长宁区卫健委医学重点(特色)专科计划项目(20232003)。

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1130.3 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14d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①HUA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)。②SMW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。③SMW、ETO和PDTC能显著降低HUA大鼠血清中IL-1β水平(P<0.05)。④SMW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)。⑤SMW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。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 1130.3 mg/(kg·d)SMW by gavage,ETO group was given 5.4 mg/(kg·d)ETO by gavage,and PDTC group was given 100 mg/(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 ABCG2 in 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.Results①HUA 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.②SMW 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 effec

关 键 词：高尿酸血症 痛风性关节炎 四妙丸 尿酸 炎症 大鼠模型 中药研究 

分 类 号：R285.5[医药卫生—中药学]