目的 通过对大鼠左侧输尿管结扎(UUO)的动物损伤模型,探讨大黄酸(rhein)和羟基红花黄色素A(HSYA)单用及配伍对肾脏保护的抗炎作用机制。方法 采用UUO 造慢性肾病损伤动物模型,将30 只雄性SD 大鼠随机分为假手术组、模型组、rhein 治疗组[100 mg/(kg·d)]、HSYA 治疗组[50 mg/(kg·d)]和rhein[100 mg/(kg·d)]＋HSYA[50 mg/(kg·d)]治疗组。给药14 d 后处死大鼠,采用试剂盒测定各组大鼠治疗前及治疗后血清中血肌酐(Scr)和尿素氮(BUN)水平,采用酶联免疫吸附法(ELISA)测定治疗前及治疗后血清肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)表达水平,通过HE 染色观察肾组织变化。结果 与模型组相比,rhein 和HSYA 单用及配伍组血清中Scr 和BUN 表达降低,差异有统计学意义(P< 0.05)。TNF-α、IL-6、IL-1β 及MCP-1 表达亦明显下降,差异有统计学意义(P< 0.01),同时肾组织病理学变化亦得到改善,且配伍的效果优于单用。结论 rhein 和HSYA 单用及配伍均能对UUO 导致的炎症损伤发挥一定的肾保护作用,配伍效果更好,其作用机制与抗炎作用有关。

Objective To investigate the kidney protection effect of rhein and Hydroxysafflower yellow A (HSYA) used alone or in combination, on unilateral ureteral obstruction (UUO) rats by inhibiting inflammatory response in rats. Methods The model of chronic kidney disease (CKD) was induced by UUO. Thirty male SD rats were divided randomly into five groups such as Sham, model, rhein 100 mg/(kg·d), HSYA 50 mg/(kg·d), and rhein 100 mg/(kg·d) + HSYA 50 mg/(kg·d) groups. All rats were killed after one month. The levels of Scr and BUN in serum were measured by kits. The inflammatory cytokines expression of TNF-α, interleukin-6, interleukin-1β, and MCP-1 by ELISA. Pathological changes were observed by HE staining. Results Compared with model rats, the levels of Scr and BUN, pathological changes and the inflammation were significantly decreased after treatment with rhein, HSYA, and rhein + HSYA, but the combined group has the better effect than using alone. Conclusion Rhein and HSYA alone and compatibility could play a protective role to the inflammatory lesions renal which caused by UUO, the mechanism may be related to its anti-inflammatory effect. Treatment that combines rhein and HSYA are superior to treatment with either drug alone.

国家自然科学基金项目(81373947)