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目的:探讨迷迭香酸对小鼠单侧输尿管梗阻(UUO)模型肾间质纤维化的抗氧化保护作用。方法:将雄性C57BL/6J小鼠随机分成3组:假手术对照组(Sham组,n=8)、UUO模型组(结扎左侧输尿管制作UUO模型,n=24)、UUO迷迭香酸干预组(UUO+RA组,n=24)。除Sham组外,其余2组根据不同的观察时间细分为3、7、14天亚组(n=8)。术后第3、7、14天分别处死各组小鼠,组织病理学方法观察肾小管间质损伤情况;Western blotting方法检测肾组织中波形蛋白(Vimentin)和E-钙黏蛋白(E-cadherin)表达;比色法测定小鼠左肾皮质匀浆中脂质过氧化标志物MDA以及抗氧化酶SOD的含量。结果:UUO模型组与假手术组比较:随着模型损伤时间的延长,肾间质损伤程度逐渐加重,Vimentin和MDA含量明显增高,E-cadherin和SOD含量明显降低。迷迭香酸干预组与UUO模型组比较:3天时肾脏病理、Vimentin、E-cadherin以及MDA、SOD含量无明显改变;7天时肾间质纤维化减轻,Vimentin、MDA含量降低,E-cadherin、SOD含量增高;14天时肾间质纤维化明显减轻,Vimentin、MDA含量明显降低,E-cadherin、SOD含量明显增高。结论:迷迭香酸可能通过减少单侧输尿管梗阻侧肾皮质脂质过氧化物的产生、增加抗氧化酶的含量,从而改善小鼠氧化应激所致的肾间质纤维化。
Objective: To investigate the protective effect of rosmarinic acid on renal interstitial fibrosis in a unilateral ureteral obstruction (UUO) model in mice. METHODS: Male C57BL/6J mice were randomly divided into 3 groups: sham operation control group (Sham group, n=8), UUO model group (ligation of left ureter to produce UUO model, n=24), UUO rosmarinic acid intervention Group (UUO+RA group, n=24). Except Sham group, the other 2 groups were subdivided into 3, 7 and 14 day subgroups (n=8) according to different observation times. All mice were sacrificed on the 3rd, 7th, and 14th day after operation. Histopathological examination of the renal tubulointerstitial damage was performed. Vimentin and E-cadherin were detected by Western blotting. Expression; Colorimetric method was used to determine the contents of lipid peroxidation marker MDA and antioxidant enzyme SOD in mouse left renal cortex homogenate. RESULTS: Compared with the sham operation group, the UUO model group and the sham operation group showed that with the prolongation of the injury time, the degree of renal interstitial injury gradually increased, the content of Vimentin and MDA increased significantly, and the content of E-cadherin and SOD decreased significantly. Compared with UUO model group, there was no significant change in renal pathology, Vimentin, E-cadherin, MDA and SOD content at 3 days; at 7 days, renal interstitial fibrosis was reduced, Vimentin, MDA content was decreased, E-cadherin, SOD content increased; renal interstitial fibrosis was significantly reduced at 14 days, Vimentin, MDA content was significantly reduced, E-cadherin, SOD content increased significantly. CONCLUSION: Rosmarinic acid may improve the renal interstitial fibrosis induced by oxidative stress in mice by reducing the production of lipid peroxides and increasing the content of antioxidant enzymes in the renal cortex of unilateral ureteral obstruction.