目的 探讨穿山龙复方水煎液对痛风性关节炎（GA）合并高尿酸血症（HUA）诱导痛风性肾病（GN）大鼠肾脏的保护作用。方法 将48只雄性SD大鼠分为6组：对照组、模型组、秋水仙碱（阳性对照，0.03 mg·kg⁻¹）组及穿山龙复方水煎液高、中、低剂量（6.300、3.150、1.575 mg·kg⁻¹）组。各给药组连续7 d ig 10 mL·kg⁻¹相应药液；对照、模型组各ig生理盐水10 mL·kg⁻¹。给药过程中，除对照组外，其余建立GA合并HUA诱导的GN模型：每天2次ip 3%的氧嗪酸钾溶液（10 mL·kg⁻¹），连续1周；在大鼠右侧踝关节后侧沿跟腱内侧以30°～40°方向插入至关节腔，将0.2 mL尿酸钠溶液（25 mg·mL⁻¹）注入到关节腔内，以关节囊对侧鼓起为注入标准，饲养过程中给予10%酵母饲料。称双侧肾脏质量，计算肾脏系数；HE染色后观察肾脏组织病理学变化；自动生化分析仪检测大鼠血尿酸（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；试剂盒法检测血清中巨噬细胞趋化蛋白-1（MCP-1）、环氧合酶-2（COX-2）、β₂-微球蛋白（β₂-Mg）及尿液中β₂-Mg水平；以实时荧光定量PCR（qRT-PCR）法测定大鼠肾脏尿酸转运蛋白1（URAT1）、有机阴离子转运体1（OAT1）、有机阴离子转运体3（OAT3）、葡萄糖转运体9（GLUT9）、ABC转运蛋白G家族成员2（ABCG2）mRNA表达。结果 与模型组比较，穿山龙复方水煎液各剂量组和秋水仙碱组的肾脏系数显著降低（P＜0.01），肾损伤明显减轻；穿山龙复方水煎液各剂量组及秋水仙碱组血清SUA、SCr、BUN、MCP-1、COX-2、β₂-Mg水平及尿液β₂-Mg水平显著降低（P＜0.05、0.01），UUA和UCr水平显著升高（P＜0.05、0.01）；肾脏URAT1、GLUT9mRNA表达显著降低（P＜0.05、0.01），OAT1、OAT3、ABCG2 mRNA表达显著升高（P＜0.05、0.01）。结论 穿山龙复方水煎液改善GN大鼠肾损伤，作用机制与抗炎，上调OAT1、OAT3、ABCG2 mRNA水平，促进UA排泄，下调URAT1、GLUT9 mRNA水平抑制UA重吸收相关。

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

黑龙江中医药大学科研基金（杰出青年培育基金）项目（2019JC02）