中国新药杂志

芹菜素对大鼠肾损伤的保护作用及机制研究

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李鹤 ¹ , 王永光 ² , 刘毅 ³ , 张宇佳 ¹ , 郑稳生 ¹

中国新药杂志 | 实验研究 2023,32(10): 1049-1056

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中国新药杂志 | 实验研究 2023, 32(10): 1049-1056

芹菜素对大鼠肾损伤的保护作用及机制研究

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李鹤¹, 王永光², 刘毅³, 张宇佳¹, 郑稳生¹

作者信息

¹北京协和医学院中国医学科学院药物研究所，药物传输技术及新型制剂北京市重点实验室，北京 100050

²安徽医科大学，合肥 230032

³安庆医药高等专科学校，安庆 246052

李鹤，女，博士，主要从事新型经皮给药制剂关键技术研究。联系电话：(010)63165233，E-mail: lihe@imm.ac.cn。

通讯作者:

郑稳生，男，研究员，主要从事中、西药物新制剂及新释药系统技术研究与开发。联系电话：(010)63165233，E-mail: zhengwensheng@imm.ac.cn。

The protective effect and mechanism of apigenin on renal injury in rats

He LI¹, Yong-guang WANG², Yi LIU³, Yu-jia ZHANG¹, Wen-sheng ZHENG¹

Affiliations

¹Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Beijing 100050, China

²Anhui Medical University, Hefei 230032, China

³Anqing Medical College, Anqing 246052, China

出版时间: 2023-05-30

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摘要

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目的：

研究芹菜素（apigenin, APG）对阿霉素诱导大鼠肾损伤的保护作用并探索其机制。

方法：

将60只实验用SD大鼠尾静脉注射阿霉素建立大鼠阿霉素肾病（adriamycin nephropathy, AN）模型，另取10只大鼠给予等体积溶媒作为空白对照组。将AN大鼠随机分为模型组、阳性对照地塞米松组（DEX组，剂量0.1 mg·kg^-1·d^-1）、APG低剂量组（APL组，剂量50 mg·kg^-1·d^-1）、APG中剂量组（APM组，剂量100 mg·kg^-1·d^-1）、APG高剂量组（APH组，剂量200 mg·kg^-1·d^-1），每组10只。DEX及APG给药组均每日灌胃治疗，正常对照组和模型组同步灌胃APG溶剂，即0.5% CMC-Na溶液，疗程60 d。测量24 h尿蛋白总量（PRO）及血清肾功能、肝功能等监测指标；HE染色法对肾脏组织进行病理学检查；免疫组化法标记肾脏组织的CD68蛋白，检测巨噬细胞在肾脏的聚集；细胞凋亡实验（TUNEL）检测肾脏细胞的凋亡情况；酶联免疫吸附法（ELISA）测定血清炎症细胞因子水平。并采用脂多糖诱导RAW264.7细胞炎症模型，观察各浓度下APG对炎症的抑制作用；采用阿霉素诱导大鼠肾小管上皮NRK-52E细胞损伤模型，观察APG对细胞损伤的保护作用。

结果：

与模型组比较，APM，APH组治疗60 d后能够显著降低肾损伤大鼠的PRO，显著减少血浆总蛋白（TP）、血尿素氮（BUN）、血肌酐（CRE）含量，改善肝功能相关指标，包括谷丙转氨酶（ALT）及谷草转氨酶（AST），APH组疗效优于DEX组；HE染色结果显示APM和APH组治疗明显改善肾脏组织病变；CD68免疫组化及TUNEL结果显示，APH组肾脏中巨噬细胞聚集显著减少，细胞凋亡也得到了改善；APH组大鼠血清炎症细胞因子白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）水平显著降低；上述差异均具有统计学意义（P<0.05，P<0.01或P<0.001）。

结论：

APG对阿霉素诱导的大鼠肾损伤具有改善作用，其机制可能与其抑制炎症及细胞保护作用有关。

关键词

肾损伤 / 芹菜素 / 阿霉素肾病 / 抗炎作用 / 细胞保护作用

Abstract

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Objective:

To study the protective effect of apigenin (APG) on adriamycin-induced renal injury in rats and explore its mechanism.

Methods:

Adriamycin nephropathy (AN) model was established by injecting doxorubicin into the tail vein of 60 SD rats, and another 10 rats were given the same volume of vehicle as control group. AN rats were randomly divided into model group, positive control dexamethasone group (DEX group, 0.1 mg·kg^-1·d^-1), APG low-dose group (APL group, 50 mg·kg^-1·d^-1), APG medium-dose group (APM group, 100 mg·kg^-1·d^-1), and APG high-dose group (APH group, 200 mg·kg^-1·d^-1), 10 rats in each group. The rats in DEX and APG groups were given daily intragastric administration, while those in the normal control group and the model group were administered with APG solvent (0.5% CMC-Na solution) for 60 days. The 24-hour proteinuria (PRO), serum renal function, liver function and other biochemical indicators were measured; the pathological examination of the kidney tissue was carried out by HE staining; the CD68 protein in the kidney tissue was marked by immunohistochemistry, and the aggregation of macrophages in the kidney was detected; the apoptosis of renal cells was detected by TUNEL apoptosis assay; the levels of serum inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS) was used to induce RAW264.7 cell inflammation model, and the inhibitory effect of APG on inflammation at different concentrations was observed; adriamycin was used to induce rat renal tubular epithelial NRK-52E cell injury model, and the effect of APG on cell injury was observed.

Results:

Compared with the model group, APM and APH could significantly reduce PRO, plasma total protein (TP), blood urea nitrogen (BUN), and serum creatinine (CRE) contents in the rats after 60 days of treatment, and improve the liver function-related indicators, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the treatment effect of the APH group was better than that of the DEX group; HE staining results showed that APM and APH treatment significantly improved renal tissue lesions; CD68 immunohistochemical and TUNEL apoptosis assay results showed that macrophage aggregation in kidneys of APH group was significantly reduced, cell apoptosis was also improved; the serum levels of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly reduced in the APH group. The above differences were statistically significant (P<0.05, P<0.01, or P<0.001).

Conclusion:

APG can improve adriamycin-induced renal injury in rats, which may be related to its anti-inflammatory and cytoprotective effects.

Key words

kidney injury / apigenin / adriamycin nephropathy / anti-inflammatory effect / cytoprotective effect

引用本文

李鹤, 王永光, 刘毅, 张宇佳, 郑稳生. 芹菜素对大鼠肾损伤的保护作用及机制研究. 中国新药杂志, 2023 , 32 (10) : 1049 -1056 .

He LI, Yong-guang WANG, Yi LIU, Yu-jia ZHANG, Wen-sheng ZHENG. The protective effect and mechanism of apigenin on renal injury in rats[J]. Chinese Journal of New Drugs, 2023 , 32 (10) : 1049 -1056 .

基金

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中国医学科学院医学与健康科技创新工程基金资助项目(2021-I2M-1-026)

参考文献

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2023年第32卷第10期

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首发时间：2026-03-05
出版时间：2023-05-30

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录用日期：2022-08-26

基金

中国医学科学院医学与健康科技创新工程基金资助项目(2021-I2M-1-026)

作者信息

¹北京协和医学院中国医学科学院药物研究所，药物传输技术及新型制剂北京市重点实验室，北京 100050

²安徽医科大学，合肥 230032

³安庆医药高等专科学校，安庆 246052

通讯作者:

郑稳生，男，研究员，主要从事中、西药物新制剂及新释药系统技术研究与开发。联系电话：(010)63165233，E-mail: zhengwensheng@imm.ac.cn。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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