浏览全部资源
扫码关注微信
- Journal Information
- Archive
- Submission
- For Reviewers
- Statement and Policies
The protective effect and mechanism of cornuside on diabetic nephropathy model mice
- ZHONGGUO YAOFANG Vol. 35, Issue 4, Pages: 395-400(2024)
- 作者机构：
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
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2024.04.03
CLC： R965Published：29 February 2024，
Received：27 July 2023，
Revised：22 November 2023，
扫 描 看 全 文
王威,甘啸阳,许惠琴等.山茱萸新苷对糖尿病肾病模型小鼠的保护作用及机制 Δ[J].中国药房,2024,35(04):395-400.
WANG Wei,GAN Xiaoyang,XU Huiqin,et al.The protective effect and mechanism of cornuside on diabetic nephropathy model mice[J].ZHONGGUO YAOFANG,2024,35(04):395-400.
王威,甘啸阳,许惠琴等.山茱萸新苷对糖尿病肾病模型小鼠的保护作用及机制 Δ[J].中国药房,2024,35(04):395-400. DOI： 10.6039/j.issn.1001-0408.2024.04.03.
WANG Wei,GAN Xiaoyang,XU Huiqin,et al.The protective effect and mechanism of cornuside on diabetic nephropathy model mice[J].ZHONGGUO YAOFANG,2024,35(04):395-400. DOI： 10.6039/j.issn.1001-0408.2024.04.03.
摘要
目的
2
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
2
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
2
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
2
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。
Abstract
OBJECTIVE
2
To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy （DN） model mice.
METHODS
2
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
2
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
2
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 products/RAGE signaling pathway.
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
Keywords
diabetic nephropathyadvanced glycation end products/the receptor of advanced glycation end products signaling pathwayinflammationrenal fibrosis
references
KIM Y K，NING X Y，MUNIR K M，et al. Emerging drugs for the treatment of diabetic nephropathy[J]. Expert Opin Emerg Drugs，2022，27（4）：417-430.
LOPEZ-VARGAS P A，TONG A，HOWELL M，et al. Educational interventions for patients with CKD：a systematic review[J]. Am J Kidney Dis，2016，68（3）：353-370.
XIONG Y B，ZHOU L L. The signaling of cellular sene-scence in diabetic nephropathy[J]. Oxid Med Cell Longev，2019，2019：7495629.
HU Q C，QU C Y，XIAO X L，et al. Flavonoids on diabetic nephropathy：advances and therapeutic opportunities[J]. Chin Med，2021，16（1）：74.
SANAJOU D，GHORBANI HAGHJO A，ARGANI H，et al. AGE-RAGE axis blockade in diabetic nephropathy：current status and future directions[J]. Eur J Pharmacol，2018，833：158-164.
STRYKER L S. Modifying risk factors：strategies that work diabetes mellitus[J]. J Arthroplasty，2016，31（8）：1625-1627.
WU R，LIU X C，YIN J Y，et al. IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice[J]. Metabolism，2018，83：18-24.
TALSMA D T，KATTA K，ETTEMA M A B，et al. Endothelial heparan sulfate deficiency reduces inflammation and fibrosis in murine diabetic nephropathy[J]. Lab Invest，2018，98（4）：427-438.
ZHANG R B，LIU J，XU B，et al. Cornuside alleviates experimental autoimmune encephalomyelitis by inhibiting Th17 cell infiltration into the central nervous system[J]. J Zhejiang Univ Sci B，2021，22（5）：421-430.
LI L C，JIN G Y，JIANG J Z，et al. Cornuside inhibits mast cell-mediated allergic response by down-regulating MAPK and NF-κB signaling pathways[J]. Biochem Biophys Res Commun，2016，473（2）：408-414.
KITADA M，OGURA Y，KOYA D. Rodent models of diabetic nephropathy：their utility and limitations[J]. Int J Nephrol Renovasc Dis，2016，9：279-290.
LIU K，XU H Q，LV G H，et al. Loganin attenuates diabetic nephropathy in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of advanced glycation end products[J]. Life Sci，2015，123：78-85.
THIPSAWAT S. Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus：a review of the literature[J]. Diab Vasc Dis Res，2021，18（6）：14791641211058856.
NIE J M，LI H F. Therapeutic effects of Salvia miltiorrhiza injection combined with telmisartan in patients with diabetic nephropathy by influencing collagen Ⅳ and fibronectin：a case-control study[J]. Exp Ther Med，2018，16（4）：3405-3412.
白璐，沈士朋，王倩，等. 通心络胶囊对糖尿病肾病模型大鼠肾纤维化的干预作用[J]. 中国药房，2023，34（13）：1584-1589.
BAI L，SHEN S P，WANG Q，et al. Intervention effect of Tongxinluo capsule on renal fibrosis in diabetic nephropathy rats[J]. China Pharm，2023，34（13）：1584-1589.
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.
LIU J L，ZHANG Y M，SHENG H Q，et al. Hyperoside suppresses renal inflammation by regulating macrophage polarization in mice with type 2 diabetes mellitus[J]. Front Immunol，2021，12：733808.
CHEN Y P，CHEN J，JIANG M，et al. Loganin and catalpol exert cooperative ameliorating effects on podocyte apoptosis upon diabetic nephropathy by targeting AGEs-RAGE signaling[J]. Life Sci，2020，252：117653.
侯凯健，郑杰洪，朱丹，等. 三七总皂苷联合氨基胍治疗对糖尿病肾病大鼠的肾脏保护作用及机制[J]. 中华中医药学刊，2020，38（8）：237-242，285-286.
HOU K J，ZHENG J H，ZHU D，et al. Renal protective effect and mechanism of Panax notoginseng saponins combined with aminoguanidine on diabetic nephropathy rats[J]. Chin Arch Tradit Chin Med，2020，38（8）：237-242，285-286.
WU X Q，ZHANG D D，WANG Y N，et al. AGE/RAGE in diabetic kidney disease and ageing kidney[J]. Free Radic Biol Med，2021，171：260-271.
PATHOMTHONGTAWEECHAI N，CHUTIPONGTANATE S. AGE/RAGE signaling-mediated endoplasmic reticulum stress and future prospects in non-coding RNA therapeutics for diabetic nephropathy[J]. Biomed Pharmacother，2020，131：110655.
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.