目的 采用多種實驗?zāi)Ｐ驮u價痛風(fēng)康寧片（TKT）對高尿酸血癥的預(yù)防作用并研究其作用機制。方法 采用ig酵母膏聯(lián)合ip氧嗪酸鉀法制備大鼠高尿酸血癥模型，酵母膏（20 g·kg^-1）連續(xù)ig 7 d，且于ig酵母膏第5天開始給藥，設(shè)置對照組、模型組和 TKT 低、中、高（0.58、1.15、2.30 g·kg^-1）組和苯溴馬隆 27 mg·kg^-1組，對照及模型組給予等容量 0.5%CMC-Na，每天 ig給藥 1次，給藥第 3天（即 ig酵母膏第 7天），ip注射氧嗪酸鉀 200 mg·kg^-1造模。檢測注射氧嗪酸鉀后 2、4 h的血清尿酸濃度、尿量、尿液中尿酸排出量及腎臟中尿酸鹽轉(zhuǎn)運體 1（URAT1）、有機陰離子轉(zhuǎn)運體 1（OAT1）、OAT3抗體表達，評價TKT對大鼠高尿酸血癥的預(yù)防作用；采用次黃嘌呤誘導(dǎo)小鼠高尿酸血癥模型，設(shè)置對照組、模型組和TKT低、中、高劑量（0.83、1.66、3.33 g·kg^-1）組及苯溴馬隆 39 mg·kg^-1組，每天 ig給藥 1次，連續(xù)給藥 5 d，對照及模型組給予等容量0.5% CMC-Na，檢測血尿酸、尿酸酶及黃嘌呤氧化酶（XOD）含量，評價TKT對小鼠高尿酸血癥的預(yù)防作用；采用大鼠水負荷模型，設(shè)置對照組和TKT低、中、高（0.58、1.15、2.30 g·kg^-1）組及氫氯噻嗪27 mg·kg^-1組，每天ig給藥1次，連續(xù)給藥 3 d，對照組給予等容量 0.5% CMC-Na，通過檢測給藥后 1、2、3、4、5 h 的尿量及給藥后 5 h 內(nèi)總尿量，評價TKT 對大鼠的利尿作用。結(jié)果 與模型組比較，TKT（0.58、1.15、2.30 g·kg^-1）能明顯降低大鼠血清尿酸濃度（P＜0.05、0.01），明顯增加尿酸排出量（P＜0.05、0.01），明顯增加腎臟OAT1的表達（P＜0.05、0.01），1.15、2.30 g·kg^-1能明顯減少腎臟 URAT1 的表達 （P＜0.05、 0.01）； TKT （1.66、 3.33 g·kg^-1） 能明顯降低小鼠血清尿酸濃度 （P＜0.05、 0.01），TKT（0.83、1.66、3.33 g·kg^-1）能明顯增加尿酸酶含量（P＜0.05、0.01）；TKT（0.58、1.15、2.30 g·kg^-1）能明顯增加給藥后不同時間點的尿量（P＜0.05、0.01），明顯增加給藥后5 h總尿量（P＜0.05、0.01）。結(jié)論 TKT通過促進尿酸分泌、抑制尿酸重吸收及利尿作用，使血清尿酸濃度明顯降低、尿尿酸排出量明顯增加，顯示對實驗性高尿酸血癥有明顯的預(yù)防作用。

Objective To evaluate of Tongfeng Kangning Tables (TKT) in the prophylactic effect and mechanism study of hyperuricemia in various experimental models.Methods A rat model of hyperuricemia was established using ig administration yeast extract in combination with ip potassium oxonate. Yeast extract (20 g·kg^-1) was ig administered for seven consecutive days, and drug administration initiated on the 5th d of yeast extract gavage, groups included a control group, a model group, low, medium, and high dose TKT groups (0.58, 1.15, 2.30 g·kg^-1), and a benzbromarone 27 mg·kg^-1 group, the control and model groups received an equal volume of 0.5% CMC-Na daily via ig administration. On the 3rd d of drug administration (the 7th d of ig yeast extract), potassium oxonate at 200 mg·kg^-1 was ip injected to induce the model. The preventive effect and mechanism of action of TKT on rat hyperuricemia were evaluated by measuring serum uric acid concentrations, urine volume, uric acid excretion in urine, at 2 h and 4 h post-injection of potassium oxonate, and the expression of URAT1, OAT1, and OAT3 antibodies in the kidneys on the 4th d of drug administration. A mice model of hyperuricemia was induced with hypoxanthine, groups consisted of control group, model group, low- , mid- , and high- dose TKT groups (0.83, 1.66, 3.33 g·kg^-1), and a benzbromarone 39 mg·kg^-1 group. These were orally administered once daily for 5 d, with control and model groups receiving an equivalent volume of 0.5% CMC-Na, the preventive effect of TKT against hyperuricemia in mice was assessed through measurements of blood uric acid levels, uricase, and XOD content. A water load model in rats was employed with groups including a control group, low, medium, and high dose TKT groups (0.58, 1.15, 2.30 g·kg^-1), and hydrochlorothiazide 27 mg·kg^-1 group. Each group was administered their respective treatments orally once daily for 3 d, while the control group received an equal volume of 0.5% CMC-Na. The diuretic effect of TKT in rats was evaluated by measuring urine volume at 1, 2, 3, 4, and 5 h post-administration, as well as the total urine output within the first 5 h.Results Compared with the model group, TKT groups were significantly reduced serum uric acid (P < 0.05, 0.01), increased the excretion of uric acid in urine, significantly increased the expression of organic anion transporter 1 (OAT1) and decreased urate transporter 1 (URAT1) in rats kidney (P < 0.05, 0.01). TKT 1.66 and 3.33 g·kg^-1 could significantly reduce serum uric acid (P < 0.05, 0.01), 0.83, 1.66 and 3.33 g·kg^-1 increased the uricase level in mice (P < 0.05, 0.01). TKT 0.58, 1.15, and 2.30 g·kg^-1 could obviously increase the urine volume at different time points and the total urine volume from 1 to 5 h after administration (P < 0.05, 0.01).Conclusion TKT reduced the concentration of serum uric acid and increased the excretion of urinary uric acid by promoted the excretion of uric acid, inhibited its reabsorption, and diuretic actions, which demonstrated significant prophylactic efficacy in experimental hyperuricemia.

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