目的 通過(guò)對(duì)大鼠左側(cè)輸尿管結(jié)扎(UUO)的動(dòng)物損傷模型,探討大黃酸(rhein)和羥基紅花黃色素A(HSYA)單用及配伍對(duì)腎臟保護(hù)的抗炎作用機(jī)制。方法 采用UUO 造慢性腎病損傷動(dòng)物模型,將30 只雄性SD 大鼠隨機(jī)分為假手術(shù)組、模型組、rhein 治療組[100 mg/(kg·d)]、HSYA 治療組[50 mg/(kg·d)]和rhein[100 mg/(kg·d)]＋HSYA[50 mg/(kg·d)]治療組。給藥14 d 后處死大鼠,采用試劑盒測(cè)定各組大鼠治療前及治療后血清中血肌酐(Scr)和尿素氮(BUN)水平,采用酶聯(lián)免疫吸附法(ELISA)測(cè)定治療前及治療后血清腫瘤壞死因子(TNF-α)、白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-1β(IL-1β)、單核細(xì)胞趨化蛋白-1(MCP-1)表達(dá)水平,通過(guò)HE 染色觀察腎組織變化。結(jié)果 與模型組相比,rhein 和HSYA 單用及配伍組血清中Scr 和BUN 表達(dá)降低,差異有統(tǒng)計(jì)學(xué)意義(P< 0.05)。TNF-α、IL-6、IL-1β 及MCP-1 表達(dá)亦明顯下降,差異有統(tǒng)計(jì)學(xué)意義(P< 0.01),同時(shí)腎組織病理學(xué)變化亦得到改善,且配伍的效果優(yōu)于單用。結(jié)論 rhein 和HSYA 單用及配伍均能對(duì)UUO 導(dǎo)致的炎癥損傷發(fā)揮一定的腎保護(hù)作用,配伍效果更好,其作用機(jī)制與抗炎作用有關(guān)。

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.

國(guó)家自然科學(xué)基金項(xiàng)目(81373947)