姜黄素对5/6肾结扎诱导的慢性肾病小鼠模型肾纤维化的保护作用
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(西南医科大学1. 附属中医医院中西医结合研究中心; 2. 附属中医医院内分泌科,泸州 646000)

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Q95-33

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Protective effect of curcumin on renal fibrosis induced by 5/6kidney ligation in the mouse model of chronic renal disease
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(1. Research Center, Affiliated Chinese Medicine Hospital of Integrated Traditional Chinese and Western Medicine.2. Department of Endocrinology, Affiliated Chinese Medicine Hospital, Southwestern Medical University,Luzhou 646000, China)

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    摘要:

    目的 研究姜黄素对慢性肾病(CKD)肾纤维化的保护作用,并探讨可能作用机制。方法 30 只C57BL/6 J 小鼠随机分成假手术对照组(NC)、5/6 肾结扎模型组(LIG)和姜黄素治疗组(LIG+CUR),每组10 只,按照改良的5/6 肾结扎方法制作CKD 动物模型,姜黄素组小鼠给予含姜黄素饲料(每日100 mg/ kg),其余组给予正常饲料,三月后牺牲小鼠,检测纤维化指标α-SMA 及参与慢性肾病纤维化的Hippo 通路转录激活子Yap。结果 肾功能检测结果显示,与假手术组相比,结扎组中的尿素氮(BUN)、血肌酐(Scr)显著增高,给予姜黄素可以有效保护肾功能受损;H&E、Masson 和免疫组化结果均显示,结扎组小鼠的肾出现明显肾小管病变和一定程度的纤维化改变,给予姜黄素后纤维化程度显著减轻( P < 0. 05);而Yap 蛋白在造模后mRNA 和蛋白水平均出现升高,姜黄素处理后则显著下降( P < 0. 05)。结论 姜黄素可有效改善5/6 肾结扎诱导的慢性肾病病症和减轻纤维化病变,机制研究结果初步提示可能与降低Hippo 信号通路中的Yap 表达有关。

    Abstract:

    Objective To study the protective effect of curcumin on renal fibrosis in chronic kidney disease (CKD) and explore its possible mechanism of action. Methods Thirty C57BL/6 J mice were randomly divided into a sham-operated control group (NC), 5/6 kidney ligation model group (LIG) and curcumin treatment group (LIG + CUR),with 10 mice in each group. The CKD animal model was prepared according to the modified 5/6 kidney ligation method.The curcumin group was given a curcumin-containing diet (100 mg/ (kg·d) and the other groups were given normal feed.The mice were euthanized after 3 months. The levels of the fibrosis index α-SMA and the Hippo pathway transcriptional activator Yap involved in fibrosis in CKD were determined. Results Renal function tests showed that urea nitrogen (BUN)and serum creatinine (Scr) were significantly increased in the LIG group compared with the NC group, and that the administration of curcumin effectively protected kidney function. H&E, Masson and immunohistochemical staining showed that the LIG kidneys had obvious tubular lesions and some fibrotic changes, and that the degree of fibrosis was significantly reduced after the administration of curcumin ( P <0. 05). The mRNA and protein levels of Yap increased after modeling,and decreased significantly after curcumin treatment ( P <0. 05). Conclusions Curcumin can significantly ameliorate the mouse CKD induced by 5/6 kidney ligation, and its mechanism may be related to a decrease of Yap in the Hippo signaling pathway.

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严颖,谭睿陟,赵长英,李健春,钟霞,王露,林晓,王丽.姜黄素对5/6肾结扎诱导的慢性肾病小鼠模型肾纤维化的保护作用[J].中国实验动物学报,2019,27(1):52~58.

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  • 收稿日期:2018-09-14
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  • 在线发布日期: 2019-03-06
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