摘要
目的探讨龙胆苦苷对高尿酸血症(HUA)小鼠的治疗作用及其潜在机制。方法对昆明小鼠腹腔注射氧嗪酸钾构建HUA模型,并给予不同剂量的龙胆苦苷进行干预。通过酶联免疫吸附检测小鼠尿酸、肌酐和黄嘌呤氧化酶的含量。利用实时荧光定量PCR和蛋白免疫印迹检测尿酸转运相关蛋白尿酸盐阴离子转运体1(URAT1)、葡萄糖转运蛋白9(GLUT9)、有机阴离子转运蛋白1(OAT1)和有机阴离子转运蛋白3(OAT3)。分析小鼠肾中白介素-1β(IL-1β)和白介素-18(IL-18)的含量,并检测NLRP3炎性小体信号通路的表达。结果与对照组相比,氧嗪酸钾构建的HUA模型尿酸、肌酐和黄嘌呤氧化酶的含量显著上调(P<0.01),尿酸转运相关蛋白GLUT9和URAT1的表达显著上升(P<0.01),OAT1和OAT3的表达明显下降(P<0.01),NLRP3炎性小体信号通路相关蛋白NLRP3、ASC和Caspase-1及通路相关炎症因子IL-1β和IL-18表达明显增加(P<0.01)。与模型组相比,动物给药龙胆苦苷干预后,尿酸、肌酐和黄嘌呤氧化酶含量显著下降(P<0.05,P<0.01),尿酸转运相关蛋白GLUT9和URAT1的表达显著下调(P<0.01),OAT1和OAT3的表达明显上升(P<0.01),NLRP3炎性小体信号通路相关蛋白NLRP3、ASC和Caspase-1及通路分泌的相关炎症因子IL-1β和IL-18表达明显降低(P<0.01)。结论龙胆苦苷可通过调控尿酸转运相关蛋白表达和抑制NLRP3炎性小体信号通路的激活,降低小鼠体内尿酸水平和缓解肾脏炎症反应,从而发挥对HUA小鼠的治疗作用。
Objective To determine the effect of gentiopicroside(Gent)on mice with hyperuricemia(HUA)via uric acid transporter proteins and NLRP3 inflammasome signaling pathways and related mechanism.Methods Kunming mice were intraperitoneally injected potassium to construct HUA model,and then the mice were given different doses of Gent.Enzyme-linked immunosorbent assay was used to determine the content of uric acid(UA),creatinine(CRE)and xanthine oxidase(XOD).Uric acid transporter-associated proteins including urate anion transporter 1(URAT1),glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and organic anion transporter 3(OAT3)were detected by real-time fluorescence quantitative PCR and Western blot.The levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the kidney of the mice were measured,and the expression of NLRP3 inflammasome signaling pathways was detected.Results Compared with the control group,potassium induced HUA model showed higher content of UA,CRE and XOD(P<0.01),higher expression of GLUT9 and URAT1(P<0.01)and lower expression of OAT1 and OAT3(P<0.01).Also higher expression of NLRP3 pathways and content of pro-inflammation cytokines(IL-1βand IL-18)were found in the HUA model.Compared with the HUA model,the mice treated with Gent had lower levels of UA,CRE,and XOD(P<0.05,P<0.01),lower expressions of GLUT9 and UART1(P<0.01)and higher expression of OAT1 and OAT3(P<0.01),the content of IL-1βand IL-18 were decreased(P<0.01).Conclusion Gent can reduce the level of UA in mice and ameliorate the kidney inflammation by regulating the expression of uric acid transporter-associated proteins and inhibiting the activation of NLRP3 inflammasome signaling pathways.
作者
区淑雅
李灿涛
邵颖颖
谢保城
胡润凯
OU Shu-ya;LI Can-tao;SHAO Ying-ying;XIE Bao-cheng;HU Run-kai(Dongguan People’s Hospital,Dongguan Guangdong 523000)
出处
《中南药学》
CAS
2021年第11期2334-2340,共7页
Central South Pharmacy
基金
广东省“十三五”中医重点专科建设项目(编号:粤中医函[2019]472号)。
关键词
高尿酸血症
肾脏炎症
尿酸转运蛋白
NLRP3炎性小体信号通路
龙胆苦苷
hyperuricemia
renal inflammation
uric acid transporter-associated protein
NLRP3 inflammasome signaling pathway
gentiopicroside
作者简介
区淑雅,女,主要从事医院药学和中药抗肿瘤方面的研究,E-mail:2225941795@qq.com;通信作者:李灿涛,男,主要从事中药活性成分抗高尿酸血症方面的研究,E-mail:815219515@qq.com。
