浏览全部资源
扫码关注微信
- Journal Information
- Archive
- Submission
- For Reviewers
- Statement and Policies
Inhibitory effects of
Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism- ZHONGGUO YAOFANG Vol. 35, Issue 2, Pages: 186-191(2024)
- 作者机构：
1.南京中医药大学翰林学院药学院，江苏 泰州 225300
2.南京中医药大学药学院，南京 210023
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2024.02.11
CLC： R965;R285.5Published：30 January 2024，
Received：28 June 2023，
Revised：21 September 2023，
扫 描 看 全 文
陈璟,杨小艺,陈静等.银杏叶提取物对糖尿病肾病模型小鼠肾脏炎症的抑制作用及机制 Δ[J].中国药房,2024,35(02):186-191.
CHEN Jing,YANG Xiaoyi,CHEN Jing,et al.Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism[J].ZHONGGUO YAOFANG,2024,35(02):186-191.
陈璟,杨小艺,陈静等.银杏叶提取物对糖尿病肾病模型小鼠肾脏炎症的抑制作用及机制 Δ[J].中国药房,2024,35(02):186-191. DOI： 10.6039/j.issn.1001-0408.2024.02.11.
CHEN Jing,YANG Xiaoyi,CHEN Jing,et al.Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism[J].ZHONGGUO YAOFANG,2024,35(02):186-191. DOI： 10.6039/j.issn.1001-0408.2024.02.11.
摘要
目的
2
探讨银杏叶提取物（GBE）抑制糖尿病肾病（DN）模型小鼠肾脏炎症的作用及其可能机制。
方法
2
以高脂高糖喂养KK/Ay小鼠建立DN模型，并分为模型组、阳性对照组[二甲双胍200 mg/（kg·d）]和GBE低、高剂量组[100、200 mg/（kg·d）]，每组6只；另取普通饲料喂养的C57BL/6J小鼠6只，作为对照组。各药物组小鼠灌胃相应药液，对照组和模型组小鼠灌胃等体积生理盐水，每天1次，连续8周。检测小鼠的体重、空腹血糖、24 h摄食量、24 h尿量和血清单核细胞趋化蛋白1（MCP-1）、白细胞介素12（IL-12）、IL-10、晚期糖基化终末产物（AGEs）、血尿素氮（BUN）、血肌酐（Scr）水平，计算其双侧肾脏质量与体重的比值，观察其肾皮质的病理损伤和纤维化改变，并检测其肾皮质中巨噬细胞极化标志蛋白[M1型：诱导型一氧化氮合酶（iNOS）；M2型：精氨酸酶1（Arg-1）]和AGEs-晚期糖基化终末产物受体（RAGE）/Ras同源基因家族成员A（RhoA/）/Rho相关螺旋卷曲蛋白激酶（ROCK）信号通路相关蛋白的表达情况。
结果
2
与模型组比较，GBE低、高剂量组小鼠肾皮质增生、空泡、炎症细胞浸润、肾皮质纤维化等症状均有所好转；其体重、血清IL-10水平、肾皮质中Arg-1蛋白的表达水平均显著高于模型组（
P
＜0.01）；空腹血糖和24 h摄食量、尿量，血清MCP-1、IL-12、BUN、Scr、AGEs水平，双侧肾脏质量与体重的比值，肾损伤评分和肾间质纤维化比例，肾皮质中iNOS、RAGE、RhoA、ROCK1（GBE低剂量组除外）蛋白的表达水平均显著低于模型组（
P
＜0.01）。
结论
2
GBE可改善DN模型小鼠的肾损伤，并减轻其炎症反应，其机制可能与抑制AGEs-RAGE/RhoA/ROCK信号通路、调节巨噬细胞极化有关。
Abstract
OBJECTIVE
2
To investigate the inhibitory effects of
Ginkgo biloba
extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism.
METHODS
2
KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex.
RESULTS
2
Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （
P
＜0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （
P
＜0.01）.
CONCLUSIONS
2
GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.
关键词
银杏叶提取物糖尿病肾病炎症反应巨噬细胞极化晚期糖基化终末产物-晚期糖基化终末产物受体/Ras同源基因家族成员A/Rho相关螺旋卷曲蛋白激酶信号通路
Keywords
diabetic nephropathyinflammationmacrophage polarizationAGEs-RAGE/RhoA/ROCK signaling pathway
references
WOLF G. New insights into the pathophysiology of diabetic nephropathy：from haemodynamics to molecular pathology[J]. Eur J Clin Invest，2004，34（12）：785-796.
SUSZTAK K，BÖTTINGER E P. Diabetic nephropathy：a frontier for personalized medicine[J]. J Am Soc Nephrol，2006，17（2）：361-367.
CUCAK H，FINK L N，PEDERSEN M H，et al. Enalapril treatment increases T cell number and promotes polarization towards M1-like macrophages locally in diabetic nephropathy[J]. Int Immunopharmacol，2015，25（1）：30-42.
LU J Y，CAO Q，ZHENG D，et al. Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease[J]. Kidney Int，2013，84（4）：745-755.
徐艳芬，张丽娟，宋新波. 银杏叶提取物的研究进展[J]. 药物评价研究，2010，33（6）：452-456.
XU Y F，ZHANG L J，SONG X B. Advances in research on extract of Ginkgo biloba leaves[J]. Drug Eval Res，2010，33（6）：452-456.
LU Q，ZUO W Z，JI X J，et al. Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy[J]. Phytomedicine，2015，22（12）：1071-1078.
庞欣欣，石秀杰，张雅歌，等. 银杏叶提取物EGB761对糖尿病肾病小鼠肾小管损伤及内质网应激的影响[J]. 中药新药与临床药理，2020，31（8）：879-886.
PANG X X，SHI X J，ZHANG Y G，et al. Effect of ginkgo leaves extract EGB761 on renal tubular injury and endoplasmic reticulum stress in mice with diabetic kidney disease[J]. Tradit Chin Drug Res Clin Pharmacol，2020，31（8）：879-886.
JIN X，YAO T Q，ZHOU Z E，et al. Advanced glycation end products enhance macrophages polarization into M1 phenotype through activating RAGE/NF-κB pathway[J]. Biomed Res Int，2015，2015：732450.
LIU Y，CHEN W H，MINZE L J，et al. Dissonant response of M0/M2 and M1 bone-marrow-derived macrophages to RhoA pathway interference[J]. Cell Tissue Res，2016，366（3）：707-720.
王威，富莹雪，陈璟，等. 梓醇对AGEs刺激巨噬细胞介导肾系膜细胞损伤的影响[J]. 中国药理学通报，2020，36（1）：110-114.
WANG W，FU Y X，CHEN J，et al. Effect of catalpol on AGEs-stimulated RAW264.7 macrophage mediated mouse mesangial cell injury[J]. Chin Pharmacol Bull，2020，36（1）：110-114.
束安梅，高雨嫣，朱逸晖，等. 梓醇抑制AGEs刺激肾内皮细胞介导巨噬细胞活化的作用研究[J]. 中国药理学通报，2020，36（11）：1513-1519.
SHU A M，GAO Y Y，ZHU Y H，et al. Inhibitory effect of catalpol on macrophage activation mediated by AGEs-stimulated mouse glomerular endothelial cells[J]. Chin Pharmacol Bull，2020，36（11）：1513-1519.
SHU A M，DU Q，CHEN J，et al. Catalpol ameliorates endothelial dysfunction and inflammation in diabetic nephropathy via suppression of RAGE/RhoA/ROCK signa-ling pathway[J]. Chem Biol Interact，2021，348：109625.
BETZ B，CONWAY B R. An update on the use of animal models in diabetic nephropathy research[J]. Curr Diab Rep，2016，16（2）：18.
CHEN J，OU Z J，GAO T T，et al. Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy[J]. Biomedicine Pharmacother，2022，156：113953.
SAKAI H，ABE K，KOBAYASHI Y，et al. Clinical guidelines of IgA nephropathy[J]. Nihon Jinzo Gakkai Shi，1995，37（8）：417-421.
KUMAR PASUPULATI A，CHITRA P S，REDDY G B. Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy[J]. Biomol Concepts，2016，7（5/6）：293-309.
RAO J L，YE Z C，TANG H，et al. The RhoA/ROCK pathway ameliorates adhesion and inflammatory infiltration induced by AGEs in glomerular endothelial cells[J]. Sci Rep，2017，7：39727.
0
Views
4
下载量
0
CSCD
- L-PDFDownload
- WORDDownload
- Meta-XMLDownload
- BibTeXDownload
- EndnoteDownload
- RefMan Download
- NoteExpressDownload
- NoteFirstDownload
Publicity Resources
Related Articles
Related Author
Related Institution
- Address：8/F,129 Daping Main Street,Yuzhong District,Chongqing 400042,P.R.China
- Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号
公网安备50010302001817 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.