目的 探討藥芹二糖苷A治療高尿酸血癥小鼠的藥效機(jī)制。方法 采用氧嗪酸鉀與腺嘌呤誘導(dǎo)高尿酸血癥小鼠模型，小鼠隨機(jī)分為對(duì)照組、模型組、苯溴馬隆組、藥芹二糖苷A（10、20 mg/kg）組。檢測(cè)小鼠血清尿酸（UA）、尿素氮（BUN）、肌酐（CRE）、白細(xì)胞介素1β（IL-1β）、白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）水平，蘇木素–伊紅（HE）染色觀察藥芹二糖苷A對(duì)小鼠腎臟病理的影響，蛋白免疫印跡法檢測(cè)腎臟核心蛋白的表達(dá)。結(jié)果 與模型組比較，藥芹二糖苷A可顯著降低模型小鼠血清UA、BUN、CRE，減少炎癥因子IL-1β、IL-6、TNF-α水平（P＜0.05、0.01）；HE顯示藥芹二糖苷A可改善腎臟囊腔水腫和腎小管萎縮，減小腎小球體積；Western blotting顯示藥芹二糖苷A可顯著升高腎臟有機(jī)陰離子轉(zhuǎn)運(yùn)體3（OAT3）蛋白表達(dá)量，降低葡萄糖轉(zhuǎn)運(yùn)體9（GLUT9）和尿酸鹽陰離子轉(zhuǎn)運(yùn)體（URAT1）蛋白表達(dá)量（P＜0.01）。結(jié)論 藥芹二糖苷A發(fā)揮治療高尿酸血癥的機(jī)制可能與改善腎功能，降低炎癥因子的釋放及調(diào)控腎臟OAT3、GLUT9和URAT1蛋白表達(dá)有關(guān)。

Objective To investigate the therapeutic mechanism of graveobioside A in treatment of hyperuricemia. Methods Potassium oxonate and adenine were used to induce hyperuricemia mouse model. The mice were randomly divided into control group, model group, benbromarone group, and graveobioside A (10, 20 mg/kg) group. The levels of serum UA, BUN, CRE, IL-1β, IL-6, and TNF-α were detected. The effects of graveobioside A on renal pathology in mice were observed by HE staining. The expression of renal core protein was detected by Western blotting. Results Compared with model group, CRE, UA, BUN, and CRE in serum of graveobioside A group were significantly decreased, and the levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were decreased (P < 0.05, 0.01). HE showed that graveobioside A could improve renal cystic edema and renal tubule atrophy, and reduce glomerular volume. Western blotting showed that graveobioside A significantly increased the expression of OAT3 protein in kidney, and decreased the expression of GLUT9 and URAT1 protein (P < 0.01). Conclusions The mechanism of graveobioside A in treatment of hyperuricemia may be related to improving renal function, reducing the release of inflammatory factors, and regulating the expression of kidney OAT3, GLUT9 and URAT1 proteins.

R285.5

河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃聯(lián)合共建項(xiàng)目(LHGJ20190273)