大黄酸配伍羟基红花黄色素A对大鼠单侧输尿管结扎慢性肾病的作用及机制研究

Effects and mechanisms of compatibility of rhein and hydroxysafflower yellow A on rat chronic kidney with unilateral ureteral obstruction

目的研究大黄酸(RH)配伍羟基红花黄色素A(HSYA)对慢性肾病(CKD)模型大鼠抗炎、抗氧化、抗凋亡能力的影响及其可能机制。方法 30只雄性SD大鼠随机分为假手术组、模型组、RH(100 mg/kg)组、HSYA(50 mg/kg)组和RH(100 mg/kg)+HSYA(50 mg/kg)组,采用单侧输尿管结扎(UUO)建立CKD模型。试剂盒法测定大鼠肾组织丙二醛(MDA)水平、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性;Masson染色观察肾组织病理变化;TUNEL染色检测细胞凋亡情况;Western blotting检测肾组织中IκBα、p-IκBα、NF-κB p-65、p-p65和Bcl-2、Bax蛋白表达。结果 RH和HSYA配伍使用明显降低MDA水平,提高SOD及GSH-Px活性;减少肾小球炎细胞浸润,改善肾小管间质纤维化等病理改变;抑制细胞凋亡;抑制磷酸化的IκBα及p65蛋白表达;使Bcl-2蛋白表达上调、Bax表达下调,且效果好于单用组。结论在CKD进程中,RH和HSYA配伍使用可抑制肾脏组织的氧化损伤,抑制肾小球炎细胞浸润,降低细胞凋亡,且效果好于两个药物单用。

Objective To investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic effects of compatibility ofrhein （RH） and hydroxy saffloweryellow A （HSYA） on rat chronic kidney with unilateral ureteral obstruction （UUO） and its mechanisms. Method The model of chronic kidney disease （CKD） was induced by UUO, 30 male SD rats were divided randomly into Sham group, model group, RH （100 mg/kg） group, HSYA （50 mg/kg） group, and RH （100 mg/kg）＋HSYA （50 mg/kg） group. The level of MDA, activities of SOD and GSH of kidney tissue were measured by kits. The kidney histological change was measured with Masson staining. The cell apotosis was analyzed using TUNEL staining. The expression of IκBα, NF-κB p65, p-IκBα, p-p65, Bcl-2, and Bax protein was examined by Western blotting. Results Compatibility of RH and HSYA significantly decreased the level of MDA and increase the activities of SOD and GSH-Px, reduced glomerular inflammatory cell infiltration, improved the renal tubular interstitial fibrosis and pathological change, inhibited apoptosis, inhibited the expression of p-!rd3a and p-p65 protein, up-regulated expression of Bcl-2 protein, and down-regulated expression of Bax, and the effects were better than those in single group. Conclusion In the process of CKD, the compatibility of HSYA and RH can inhibit the oxidative damage of renal tissue, inhibit the infiltration of inflammatory cells and reduce apoptosis, and the effect is better than that of the two drugs alone.