对清利湿热方降低高尿酸血症湿热内蕴证大鼠血尿酸的作用及机制研究  

Study on the mechanism of lowering urate levels of Qinglishire Prescription in a rat model of hyperuricemia with syndrome of internal retention of damp-heat

作　　者：刘金莲 吕美豫 南海鹏 邸松蕊 梁唯灿 王林元[2] 张建军 王淳 LIU Jinlian;LYU Meiyu;NAN Haipeng;DI Songrui;LIANG Weican;WANG Linyuan;ZHANG Jianjun;WANG Chun(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;School of Traditional Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中医学院 [2]北京中医药大学中药学院

出　　处：《北京中医药大学学报》2022年第12期1257-1265,共9页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家重点研发计划“中医药现代化研究”专项(No.2018YFC1706803)。

摘　　要：目的通过观察清利湿热方(土茯苓、车前子、茯苓、菊苣、葛根、川牛膝)降低高尿酸血症湿热内蕴证大鼠血尿酸的作用,探讨其作用机制。方法采用灌胃氧嗪酸钾,饲喂高脂高糖饲料,并复合隔天灌胃油脂或酒,自由饮用蜂蜜水(100 g/L)复制高尿酸血症大鼠模型。将SD大鼠按体质量分为正常组、模型组、四妙丸组(1.2 g/kg)、清利湿热方低剂量组(1.25 g/kg)、清利湿热方中剂量组(2.5 g/kg)、清利湿热方高剂量组(5.0 g/kg),每天上午造模,下午给药,连续30 d。分离血清,取肝、肾,检测各组大鼠血清尿酸(UA)、尿素氮(BUN)、肌酐(Scr)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、IgG、IgM、NO、内皮素-1(ET-1)、血栓素(TX)-B2、6-酮前列素F1α(6-keto-PGF1α)含量,肝脏组织Na^(+)-K^(+)-ATP酶含量,肾脏组织中三磷酸腺苷结合转运蛋白2(ABCG2)及尿酸盐转运蛋白1(URAT1)蛋白表达量,肾脏组织ABCG2、URAT1及葡萄糖转运体9(GLUT9)mRNA表达量,胃组织水通道蛋白3(AQP3)、水通道蛋白4(AQP4)含量。结果(1)与模型组比较,清利湿热方各剂量组及四妙丸组血清UA、ET-1、TX-B2、IL-4及胃AQP4含量降低(P<0.01,P<0.05),肝脏Na^(+)-K^(+)-ATP酶含量增加(P<0.01);高剂量组血清NO含量增加(P<0.01);中剂量组血清6-keto-PGF1α含量增加(P<0.01);中、高剂量组胃AQP3含量增加(P<0.05);低、中、高剂量组血清IgG含量降低(P<0.05,P<0.01);中、高剂量组及四妙丸组血清IgM含量降低(P<0.05,P<0.01)。(2)与模型组比较,四妙丸组及清利湿热方中、高剂量组URAT1 mRNA表达下调(P<0.05,P<0.01);各给药组GLUT9 mRNA表达下调(P<0.05,P<0.01);各给药组ABCG2 mRNA表达均上调(P<0.01)。各给药组URAT1蛋白表达均降低(P<0.05,P<0.01)。结论清利湿热方具有降血尿酸作用,其降尿酸机制与下调URAT1基因与蛋白质表达、上调ABCG2基因与蛋白质表达及下调GLUT9基因表达有关。Objective We aimed to observe the effect of lowering urate level of Qinglishire(clearing heat and promoting diuresis)Prescription(QLSR)(glabrous greenbrier rhizome,plantain seed,Indian bread,chicory,kudzuvine root,and medical cyathula root)in rats with hyperuricemia with syndrome of internal retention of damp-heat.Methods The rat model of hyperuricemia was established by feeding rats with high-fat and high-sugar diet and administering potassium oxonate and oil or alcohol every other day.Sprague-Dawley rats were divided into six groups:the normal group,the model group,the Simiao Pill group(1.2 g/kg),and the QLSR low-,medium-,and high-dose groups(1.25,2.5,and 5.0 g/kg,respectively).We observed the general state of rats.Serum uric acid(UA),urea nitrogen(BUN),creatinine(Scr),IL-2,IL-4,IgG,IgM,NO,endothelin-1(ET-1),thromboxane(TX)-B2,and 6-keto-PGF1αlevels and hepatic Na^(+)-K^(+)-ATPase levels were determined.The protein expression levels of ATP-binding cassette sub-family G member 2(ABCG2)and urate transporter 1(URAT1)in kidney tissuewere determined by Western blotting analysis;the mRNA expression levels of ABCG2,URAT1,and glucose transporter 9(GLUT9)in rat kidney tissue were detected by PCR;and the protein contents of AQP3 and AQP4 in gastric tissuewere detected by immunohistochemistry.Results(ⅰ)Compared with the model group,QLSR low-,medium-,high-dose and Simiao Pill decreased serum UA,ET-1,TX-B2,IL-4 and gastric AQP4(P<0.01,P<0.05),and increased hepatic Na^(+)-K^(+)-ATPase(P<0.01).Serum NO was increase in QLSR high-dose group(P<0.01)and serum 6-keto-PGF1αwas increased in QLSR medium-dose group(P<0.01).Gastric AQP3 were increased in QLSR medium-and high-dose groups(P<0.05).Serum IgG were decreased in all QLSR groups(P<0.01,P<0.05),while serum IgM were decreased in QLSR medium-,high-dose and Simiao Pill group(P<0.01,P<0.05).(ⅱ)Simiao Pill and QLSR medium-and high-dose downregulated URAT1 mRNA expressions(P<0.01,P<0.05).QLSR low-,medium-,high-dose and Simiao Pill all downregulated expressions of LUT9 mRNA(P<0.

关 键 词：高尿酸血症 湿热内蕴证 清利湿热法 尿酸转运蛋白 药食两用 大鼠 

分 类 号：R285.5[医药卫生—中药学]