健脾渗湿解毒汤对高尿酸血症大鼠的作用及机制探讨  

Discussion of Effect and Mechanism of Jianpi Shenshi JieduDecoction on Hyperuricemia Rats

作　　者：叶文静 杨文奎[1] 符芸瑜 吴小翠[1] 邱晓堂[1] YE Wenjing;YANG Wenkui;FU Yunyu;WU Xiaocui;QIU Xiaotang(Hainan Traditional Chinese Medicine Hospital,Haikou 570203,China)

机构地区：[1]海南省中医院,海口570203

出　　处：《中国中医基础医学杂志》2024年第1期41-45,共5页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：海南省重点研发项目(ZDYF2020161);海南省重大科技项目(ZDKJ2021034);国家中医药管理局高水平中医药重点学科中医老年医学建设项目(琼卫中医函[2023]3号)。

摘　　要：目的 通过观察健脾渗湿解毒汤对高尿酸血症(hyperuricemia,HUA)模型大鼠尿酸盐转运蛋白表达的影响,探讨该方治疗HUA的作用机制。方法 取健康雄性SD大鼠60只,随机分为空白对照组、模型组、苯溴马隆组和健脾渗湿解毒汤低、中、高剂量组。除空白对照组大鼠给予灌胃蒸馏水外,其他各组大鼠分别灌胃氧嗪酸钾和腺嘌呤建立HUA模型,各药物治疗组大鼠在造模1 h后予相应药物灌胃,持续给药21 d后处死,检测各组大鼠血尿酸(serum uric acid,SUA)、血肌酐(serum creatinine,SCR)、尿素氮(blood urea nitrogen,BUN)、谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)含量;苏木素-伊红(hematoxylin-eosin,HE)染色观察肾脏及肝脏组织病理学变化;Western blot和实时荧光定量PCR法检测肾脏组织尿酸盐转运蛋白(urate transporter,URAT)1、有机阴离子转运蛋白(organic anion transporter,OAT)3的表达。结果 与空白对照组比较,模型组大鼠血清SUA、SCR含量明显升高(P<0.05),肾脏组织中URAT1蛋白和m RNA的表达水平明显升高(P<0.01)、OAT3蛋白和m RNA的表达水平明显降低(P<0.01)。与模型组比较,健脾渗湿解毒汤低剂量组大鼠SUA含量明显降低(P<0.01),健脾渗湿解毒汤中剂量和高剂量组大鼠SUA、SCR、BUN含量均明显降低(P<0.05)。此外,高剂量健脾渗湿解毒汤能够明显降低URAT1蛋白及m RNA(P<0.05)、升高OAT3蛋白及m RNA的表达水平(P<0.05),减轻肾脏损伤。结论 健脾渗湿解毒汤有显著的降尿酸效果,具体机制可能与其抑制尿酸重吸收蛋白URAT1、上调尿酸分泌蛋白OAT3的表达相关。Objective To observe the effect of Jianpi Shenshi Jiedu decoction on urate transporter expression in hyperuricemia(HUA)model rats,and explore the mechanism of Jianpi Shenshi Jiedu decoction in the treatment of hyperuricemia.Methods A total of 60 healthy male SD rats were randomly divided into control group,model group,benzbromarone group,and low,medium and high dose groups of Jianpi Shenshi Jiedu decoction.Except the control group was given distilled water,the other groups were intragastrically administered with potassium oxonate and adenine to establish a HUA rat model.One hour after intragastric administration of potassium oxonate and adenine,the rats were given corresponding drugs by gavage,then sacrificed after 21 days.Serum samples were collected to detect the content of serum uric acid(SUA),serum creatinine(SCR),blood urea nitrogen(BUN),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in rats.HE staining was used to observe morphological changes in kidney and liver tissues.The protein and mRNA levels of urate transporter(URAT)1 and organic anion transporter(OAT)3 were detected by Western blot and real-time qPCR.Results Compared with the control group,the levels of SUA and SCR,and the protein and mRNA level of URAT1 in the model group rats were significantly increased(P<0.05),while the protein and mRNA level of OAT3 was significantly decreased(P<0.01).Compared with the model group,the level of SUA in the Jianpi Shenshi Jiedu decoction low-dose group was significantly decreased(P<0.01),and the levels of SUA,SCR and BUN in Jianpi Shenshi Jiedu decoction medium-dose and high-dose groups were significantly decreased(P<0.05).In addition,high-dose Jianpi Shenshi Jiedu decoction could reduce the protein and mRNA level of URAT1(P<0.01),increase the protein and mRNA level of OAT3(P<0.05),and alleviate kidney injury.Conclusion Jianpi Shenshi Jiedu decoction has a significant uric acid lowering effect.Its mechanism may be related to the down-regulation of uric acid reabsorption protein URAT1 and the up-r

关 键 词：高尿酸血症 健脾渗湿解毒汤 尿酸盐转运蛋白1 有机阴离子转运蛋白3 

分 类 号：R285.5[医药卫生—中药学]