Page 17 - 《中国药房》2024年4期

·药学研究·

山茱萸新苷对糖尿病肾病模型小鼠的保护作用及机制
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王 威 ，甘啸阳，许惠琴 ，朱逸晖，束安梅，富莹雪，喻 斌，吕高虹（南京中医药大学药学院/江苏省中药药效与
安全性评价重点实验室，南京 210023）

中图分类号 R965 文献标志码 A 文章编号 1001-0408（2024）04-0395-06
DOI 10.6039/j.issn.1001-0408.2024.04.03

摘 要 目的 探讨山茱萸新苷对糖尿病肾病（DN）模型小鼠的保护作用及潜在机制。方法 将雄性KK-Ay小鼠以高脂高糖饲料
喂养2周复制DN小鼠模型。将造模成功的小鼠随机分为模型组、氨基胍组（阳性对照，100 mg/kg）、山茱萸新苷组（100 mg/kg），另
取雄性C57BL/6J小鼠作为正常组，每组6只。各药物组小鼠灌胃相应药液，正常组和模型组小鼠灌胃等体积生理盐水，每天1次，
连续8周。检测各组小鼠空腹血糖（FBG）、24 h尿蛋白，血清白细胞介素12（IL-12）、IL-10、尿素氮（BUN）、肌酐（Scr）水平，观察其
肾组织病理损伤、纤维化改变和肾小球微观结构，检测其肾皮质中晚期糖基化终末产物受体（RAGE）、Ⅳ型胶原（COL-Ⅳ）、诱导型
一氧化氮合酶（iNOS）蛋白的表达情况。结果 与正常组比较，模型组小鼠肾皮质可见明显的炎症细胞浸润和纤维化改变，肾小球
系膜增生严重且基底膜有大量不规则块状暗色致密物沉积；其FBG、24 h尿蛋白水平，血清IL-12、BUN、Scr水平，肾皮质RAGE、
COL-Ⅳ、iNOS蛋白的表达量均显著升高，血清IL-10水平显著降低（P＜0.01）。与模型组比较，各药物组小鼠肾脏病理损伤、纤维
化改变及肾小球微观结构均有明显改善，上述各定量指标均普遍好转（P＜0.05或P＜0.01）。结论 山茱萸新苷对DN模型小鼠具
有一定的保护作用，可抑制炎症反应，降低尿蛋白水平，缓解肾脏纤维化；上述作用可能与抑制晚期糖基终末产物/RAGE信号通
路有关。
关键词 山茱萸新苷；糖尿病肾病；晚期糖基化终末产物/晚期糖基化终末产物受体信号通路；炎症；肾脏纤维化

The protective effect and mechanism of cornuside on diabetic nephropathy model mice
WANG Wei，GAN Xiaoyang，XU Huiqin，ZHU Yihui，SHU Anmei，FU Yingxue，YU Bin，LYU Gaohong（College
of Pharmacy， Nanjing University of Chinese Medicine/Jiangsu Key Laboratory for Pharmacology and Safety
Evaluation of Chinese Materia Medica， Nanjing 210023， China）

ABSTRACT OBJECTIVE To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy
（DN） model mice. METHODS Male KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN
model. The successfully modeled mice were randomly grouped into model group， aminoguanidine group （positive control，100
mg/kg） and cornuside group （100 mg/kg）， and male C57BL/6J mice were included as normal group， with 6 mice in each group.
Administration groups were given relevant medicine intragastrically， and normal group and model group were given a constant
volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The levels of fasting blood glucose （FBG）， 24 h
urinary protein， serum interleukin-12 （IL-12）， IL-10， blood urea nitrogen （BUN） and serum creatinine （Scr） were detected； the
pathological injury， fibrotic change and glomerular microstructure of renal tissue were observed； the expressions of the receptor of
advanced glycation end products （RAGE）， collagen type Ⅳ （COL-Ⅳ） and inducible nitric oxide synthase （iNOS） in renal cortex
were detected in each group. RESULTS Compared with normal group， the renal cortex of mice in model group showed obvious
inflammatory cell infiltration and fibrotic changes； the mesangial hyperplasia of glomerulus was serious and the basement
membrane had a large number of irregular dark dense deposits； the levels of FBG and 24 h urinary protein， the serum levels of IL-
12， BUN and Scr， and the expression levels of RAGE， COL-Ⅳ and iNOS in the renal cortex were significantly increased， while
the serum level of IL-10 was significantly decreased （P＜0.01）. Compared with the model group， the renal pathological injuries，
fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly， and the above
quantitative indexes were generally improved （P＜0.05 or P＜0.01）. CONCLUSIONS Cornuside has a certain protective effect on
DN model mice. It can inhibit the inflammatory response， reduce urinary protein excretion， and alleviate renal fibrosis， which may
be related to the inhibition of the advanced glycation end
Δ 基金项目 国家自然科学基金项目（No.81874359）
＊第一作者 助理实验师，硕士。研究方向：中药内分泌药理学。 products/RAGE signaling pathway.
E-mail：wangwei4486927@163.com KEYWORDS cornuside； diabetic nephropathy； advanced
# 通信作者 教授，博士生导师，博士。研究方向：中药内分泌药理 glycation end products/the receptor of advanced glycation end
学。E-mail：hqxu309@sina.com products signaling pathway； inflammation； renal fibrosis

中国药房 2024年第35卷第4期 China Pharmacy 2024 Vol. 35 No. 4 · 395 ·