目的 探討穿山龍復方水煎液對痛風性關(guān)節(jié)炎（GA）合并高尿酸血癥（HUA）誘導痛風性腎病（GN）大鼠腎臟的保護作用。方法 將48只雄性SD大鼠分為6組：對照組、模型組、秋水仙堿（陽性對照，0.03 mg·kg⁻¹）組及穿山龍復方水煎液高、中、低劑量（6.300、3.150、1.575 mg·kg⁻¹）組。各給藥組連續(xù)7 d ig 10 mL·kg⁻¹相應藥液；對照、模型組各ig生理鹽水10 mL·kg⁻¹。給藥過程中，除對照組外，其余建立GA合并HUA誘導的GN模型：每天2次ip 3%的氧嗪酸鉀溶液（10 mL·kg⁻¹），連續(xù)1周；在大鼠右側(cè)踝關(guān)節(jié)后側(cè)沿跟腱內(nèi)側(cè)以30°～40°方向插入至關(guān)節(jié)腔，將0.2 mL尿酸鈉溶液（25 mg·mL⁻¹）注入到關(guān)節(jié)腔內(nèi)，以關(guān)節(jié)囊對側(cè)鼓起為注入標準，飼養(yǎng)過程中給予10%酵母飼料。稱雙側(cè)腎臟質(zhì)量，計算腎臟系數(shù)；HE染色后觀察腎臟組織病理學變化；自動生化分析儀檢測大鼠血尿酸（SUA）、血肌酐（SCr）、血清尿素氮（BUN）水平以及尿液尿酸（UUA）、尿肌酐（UCr）水平；試劑盒法檢測血清中巨噬細胞趨化蛋白-1（MCP-1）、環(huán)氧合酶-2（COX-2）、β₂-微球蛋白（β₂-Mg）及尿液中β₂-Mg水平；以實時熒光定量PCR（qRT-PCR）法測定大鼠腎臟尿酸轉(zhuǎn)運蛋白1（URAT1）、有機陰離子轉(zhuǎn)運體1（OAT1）、有機陰離子轉(zhuǎn)運體3（OAT3）、葡萄糖轉(zhuǎn)運體9（GLUT9）、ABC轉(zhuǎn)運蛋白G家族成員2（ABCG2）mRNA表達。結(jié)果 與模型組比較，穿山龍復方水煎液各劑量組和秋水仙堿組的腎臟系數(shù)顯著降低（P＜0.01），腎損傷明顯減輕；穿山龍復方水煎液各劑量組及秋水仙堿組血清SUA、SCr、BUN、MCP-1、COX-2、β₂-Mg水平及尿液β₂-Mg水平顯著降低（P＜0.05、0.01），UUA和UCr水平顯著升高（P＜0.05、0.01）；腎臟URAT1、GLUT9mRNA表達顯著降低（P＜0.05、0.01），OAT1、OAT3、ABCG2 mRNA表達顯著升高（P＜0.05、0.01）。結(jié)論 穿山龍復方水煎液改善GN大鼠腎損傷，作用機制與抗炎，上調(diào)OAT1、OAT3、ABCG2 mRNA水平，促進UA排泄，下調(diào)URAT1、GLUT9 mRNA水平抑制UA重吸收相關(guān)。

Objective To investigate the protective effect of diostrodia compound decoction (DCD) on the kidney of gout arthritis (GA) & hyperuricemia (HU) -induced gout nephropathy (GN) rats. Methods Forty-eight male SD rats were divided into six groups, namely control, model, colchicine (positive controls, 0.03 mg·kg⁻¹) and DCD high, medium and low dose (6.300, 3.150, and 1.575 mg·kg⁻¹) groups. While moulding with sodium urine acid, potassium oxyzine, and high-fat diet, the corresponding drugs were gavaged, respectively. Kidney histopathology was observed after 7 d, Kidney index was calculated, The serum uric acid (SUA), creatinine (SCr), urea nitrogen (BUN) levels, as well as the serum levels of MCP-1, COX-2, and β₂-Mg, were measured in rats, Urine uric acid (UUA), urinary creatinine (UCr) levels, as well as urine β₂-Mg levels in rats, The mRNA expression of rat kidney uric acid transporter 1 (URAT1), organic anion transporter (OAT), glucose transporter, ABC transporter 9 (GLUT9), and G family members 2 (ABCG2) was determined by the Real-time PCR(qRT-PCR) assay. Results Compared with model group, the kidney index was decreased in both the dose group and the colchicine groups (P < 0.01). The levels of serum SUA, SCr, BUN, MCP-1, COX-2 and β₂-Mg and urine β₂-Mg in DCD groups and colchicine groups were significantly decreased (P < 0.05, 0.01), and the levels of UUA and UCr were significantly increased (P < 0.05, 0.01). The mRNA expressions of URAT1 and GLUT9 in kidney were significantly decreased (P < 0.05, 0.01), and the mRNA expressions of OAT1, OAT3 and ABCG2 were significantly increased (P < 0.05, 0.01). Conclusion DCD improved kidney injury in GN rats, and the mechanism was related to anti-inflammatory, upregulating OAT1, OAT3 and ABCG2 levels to promote UA excretion, down-regulating URAT1 and GLUT9 levels to inhibit UA reabsorption.

R285

黑龍江中醫(yī)藥大學科研基金（杰出青年培育基金）項目（2019JC02）