[1]吴 冰,王 轩.基于Notch信号通路探讨枸杞多糖对糖尿病肾病大鼠肾纤维化的改善作用[J].陕西医学杂志,2023,52(3):267-272.[doi:DOI:10.3969/j.issn.1000-7377.2023.03.005]
 WU Bing,WANG Xuan.Improvement effect of lycium barbarum polysaccharide on renal fibrosis in diabetic nephropathy rats based on Notch pathway[J].,2023,52(3):267-272.[doi:DOI:10.3969/j.issn.1000-7377.2023.03.005]
点击复制

基于Notch信号通路探讨枸杞多糖对糖尿病肾病大鼠肾纤维化的改善作用
分享到:

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年3期
页码:
267-272
栏目:
基础研究
出版日期:
2023-03-05

文章信息/Info

Title:
Improvement effect of lycium barbarum polysaccharide on renal fibrosis in diabetic nephropathy rats based on Notch pathway
作者:
吴 冰1王 轩2
(1.辽宁省金秋医院检验科,辽宁 沈阳 110016; 2.大连市中心医院检验科,辽宁 大连 116033)
Author(s):
WU BingWANG Xuan
(Department of Clinical Laboratory,Liaoning Jinqiu Hospital,Shenyang 110016,China)
关键词:
糖尿病肾病 肾纤维化 枸杞多糖 Notch信号通路 肾功能 大鼠
Keywords:
Diabetic nephropathy Renal fibrosis Lycium barbarum polysaccharide Notch signaling pathway Renal function Rats
分类号:
R 587.2
DOI:
DOI:10.3969/j.issn.1000-7377.2023.03.005
文献标志码:
A
摘要:
目的:探究枸杞多糖(LBP)对糖尿病肾病(DN)大鼠肾纤维化的改善作用,并初步探究其可能的作用机制。方法:将SD大鼠分为对照组、模型组(DN组)、LBP组、Notch1抑制剂组(FLI-06组)、LBP+FLI-06组,每组10只。采用全自动生化分析仪对空腹血糖(FBG)和肾功能指标[血尿素氮(BUN)、血肌酐(Scr)、24 h尿微量白蛋白(UMA)]水平。采用放射免疫法检测血清纤维化相关因子[透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(C-Ⅳ)]水平。采用HE染色、Masson染色、透射电镜观察大鼠肾组织形态结构变化。采用免疫印迹和免疫组化法检测肾组织Notch信号通路相关蛋白(Notch1、Jagged1、Hes1)表达水平及阳性表达情况。结果:与对照组比较,其他四组FBG、BUN、Scr、24 h尿UMA、HA、LN、PCⅢ、C-Ⅳ水平升高,肾组织损伤评分、胶原纤维比例升高,Notch1、Jagged1、Hes1蛋白表达水平及阳性表达率升高(均P<0.05)。与DN组比较,LBP组、FLI-06组、LBP+FLI-06组FBG、BUN、Scr、24 h尿UMA、HA、LN、PCⅢ、C-Ⅳ水平降低,肾组织损伤评分、胶原纤维比例降低,Notch1、Jagged1、Hes1蛋白表达水平及阳性表达率下降(均P<0.05)。LBP+FLI-06组FBG、BUN、Scr、24 h尿UMA、HA、LN、PCⅢ、C-Ⅳ水平,肾组织损伤评分,胶原纤维比例,以及Notch1、Jagged1、Hes1蛋白表达水平及阳性表达率低于LBP组和FLI-06组(均P<0.05)。HE染色、Masson染色和透射电镜检查结果表明,DN组肾组织相对于对照组出现病理损伤,纤维化增多,LBP组、FLI-06组、LBP+FLI-06组肾组织病理损伤情况均得到改善,其中LBP+FLI-06组改善最为显著。结论:LBP可改善DN大鼠肾纤维化,其机制可能与抑制Notch信号通路活化有关。
Abstract:
Objective:To explore the improvement effect of lycium barbarum polysaccharide(LBP)on renal fibrosis in diabetic nephropathy(DN)rats based on Notch pathway.Methods:SD rats were divided into control group,model group(DN group),LBP group,Notch1 inhibitor group(FLI-06 group),LBP+FLI-06 group,with 10 rats in each group.The levels of fasting blood glucose(FBG)and renal function indexes [blood urea nitrogen(BUN),serum creatinine(Scr),24-hour urinary microalbumin(UMA)] were measured by automatic biochemical analyzer.The levels of serum fibrosis-related factors [hyaluronic acid(HA),laminin(LN),type Ⅲ procollagen(PCⅢ),and type Ⅳ collagen(C-Ⅳ)] were detected by radioimmunoassay.HE staining,Masson staining and transmission electron microscopy were used to observe the morphological changes of renal tissue.Western blot and immunohistochemistry were used to detect the expression levels and positive expressions of Notch pathway-related proteins(Notch1,Jagged1,Hes1)in renal tissues.Results:Compared with the control group,the levels of FBG,BUN,Scr,UMA,HA,LN,PCⅢ,C-Ⅳ,renal tissue injury score,collagen fiber proportion,Notch1,Jagged1,Hes1 protein expression levels and positive expression rates were increased in the other four groups(all P<0.05).Compared with DN group,the levels of FBG,BUN,Scr,UMA,HA,LN,PCⅢ and C-Ⅳ in LBP group,FLI-06 group and LBP+FLI-06 group were decreased,and the renal tissue damage score and the proportion of collagen fibers were decreased,and the protein expression levels and positive expression rates of Notch1,Jagged1 and Hes1 were decreased(all P<0.05).Compared with the LBP group and the FLI-06 group,the LBP+FLI-06 group had significantly lower levels of FBG,BUN,Scr,UMA,HA,LN,PCⅢ,C-Ⅳ,renal tissue damage score,collagen fiber proportion,and protein expression levels and positive expression rates of Notch1,Jagged1,Hes1(all P<0.05).The results of HE staining,Masson staining and transmission electron microscopy showed that the DN group had pathological damage and increased fibrosis compared with the control group,and the LBP group,FLI-06 group and LBP+FLI-06 group had improved pathological damage of renal tissue,and the LBP+FLI-06 group had the most significant improvement.Conclusion:Lycium barbarum polysaccharide can improve renal fibrosis in DN rats.The mechanism may be related to inhibition of the activation of Notch signaling pathway.

参考文献/References:

[1] 郭凯锋,陈海冰,贾伟平.糖尿病肾脏疾病的流行病学进展[J].医学研究杂志,2015,44(3):162-166.
[2] Sabapathy V,Stremska ME,Mohammad S,et al.Novel immunomodulatory cytokine regulates inflammation,diabetes,and obesity to protect from diabetic nephropathy[J].Front Pharmaco,2019,10(5):572-578.
[3] 徐艳艳,范秋灵,丁 红,等.高糖诱导肾小球系膜细胞Notch信号通路活化及百令提取液的干预作用[J].中华肾脏病杂志,2016,32(2):132-137.
[4] Cai H,Liu F,Zuo P,et al.Practical application of antidiabetic efficacy of lycium barbarum polysaccharide in patients with type 2 diabetes[J].Med Chem,2015,11(4):383-390.
[5] 周 欢,田 娜,吴丽华,等.枸杞多糖缓解单侧输尿管梗阻模型大鼠肾损伤及氧化应激反应[J].中华肾脏病杂志,2018,34(5):377-384.
[6] 管志敏,柏晓辉,屈 璐,等.小剂量多次腹腔注射链脲佐菌素建立糖尿病肾病大鼠模型[J].贵州医科大学学报,2016,41(1):54-56.
[7] 黄云兰,梁 耿,韦凯东.枸杞多糖对大鼠糖尿病的作用研究[J].中国实验方剂学杂志,2012,18(22):275-278.
[8] Kramer A,Mentrup T,Kleizen B,et al.Small molecules intercept Notch signaling and the early secretory pathway[J].Nat Chem Biol,2013,9(11):731-738.
[9] 薛海燕,李振江,孔令强.不同分期糖尿病肾病患者25羟维生素D、低氧诱导因子-1α检测及临床意义[J].陕西医学杂志,2021,50(5):614-617.
[10] 刘 芳,张立祥,王慧敏,等.养生益肾汤对糖尿病肾病患者血清细胞因子水平及肾功能的影响[J].陕西中医,2022,43(4):476-478,486.
[11] 屈雅娟,张敬芳,孙 旗,等.灯盏细辛联合依帕司他对糖尿病肾病模型大鼠的治疗作用及机制[J].陕西中医,2022,43(10):1337-1341.
[12] 袁 瑾,赵 灿,张渭涛.依普利酮通过靶向微小RNA-192和微小RNA-29a/b/c 减轻糖尿病肾病模型大鼠肾损伤机制研究[J].陕西医学杂志,2022,51(3):293-297,302.
[13] Mohan T,Velusamy P,Chakrapani LN,et al.Impact of EGCG supplementation on the progression of diabetic nephropathy in rats:An insight into fibrosis and apoptosis[J].J Agric Food Chem,2017,65(36):8028-8036.
[14] 孟 姣,吕振宇,孙传鑫,等.枸杞多糖药理作用研究进展[J].时珍国医国药,2018,29(10):191-195.
[15] Du M,Hu X,Kou L,et al.Lycium barbarum polysaccharide mediated the antidiabetic and antinephritic effects in diet-streptozotocin-induced diabetic sprague dawley rats via regulation of NF-κB [J].Biomed Res Int,2016,2016:3410290.
[16] Huang Y,Zhou F,Shen C,et al.LBP reduces theinflammatory injuryof kidney in septic rat and regulates the Keap1-Nrf2/ARE signaling pathway1[J].Acta Cir Bras,2019,34(1):3-10.
[17] Liu M,Ning X,Li R,et al.Signalling pathways involved in hypoxia-induced renal fibrosis[J].J Cell Mol Med,2017,21(7):1248-1259.
[18] 朱丽华,熊御云,夏 琳,等.积雪草酸预处理对脓毒症小鼠急性肾损伤的影响及机制[J].山东医药,2017,57(30):10-13.
[19] 谭禹洁,朱春玲,毛华雄.黄芩苷对单侧输尿管梗阻肾间质纤维化大鼠模型的治疗作用及机制研究[J].中国当代儿科杂志,2016,18(4):365-371.
[20] Chen X,Wu Y,Diao Z,et al.C1q/tumor necrosis factor-related protein-3 improves renal fibrosis via inhibiting notch signaling pathways[J].J Cell Physiol,2019,234(5):6463-6476.
[21] Tian H,Yang J,Xie Z,et al.Gliquidone alleviates diabetic nephropathy by inhibiting Notch/snail signaling pathway[J].Cell Physiol Biochem,2018,51(5):2085-2097.
[22] Yang G,Zhao Z,Zhang X,et al.Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice[J].Drug Des Devel Ther,2017,11(5):1065-1079.

相似文献/References:

[1]袁江红.腹膜透析与血液透析治疗终末期糖尿病肾病患者疗效比较[J].陕西医学杂志,2016,(10):1365.
[2]徐 琳,贾睿博△,宋民喜,等.颗粒蛋白前体与糖尿病肾病关系探讨*[J].陕西医学杂志,2019,(8):1024.
[3]李 明,门 敏△,王丽萍,等.瑞舒伐他汀联合前列地尔治疗早期糖尿病肾病疗效研究*[J].陕西医学杂志,2019,(9):1223.
 LI Ming,MEN Min,WANG Liping,et al.Efficacy of rosuvastatin combined with alprostadil in the 〖JZ〗treatment of early diabetic nephropathy[J].,2019,(3):1223.
[4]徐 琳,贺菲菲△.糖尿病肾病患者血清铁代谢指标与尿蛋白排泄量相关性分析*[J].陕西医学杂志,2019,(10):1281.
 XU Ling,HE Feifei..Correlation between serum iron metabolism index and urine protein 〖JZ〗excretion in patients with diabetic nephropathy[J].,2019,(3):1281.
[5]高旭航,郑玉群,何志杰,等.基因多态性与糖尿病肾病关系研究进展[J].陕西医学杂志,2019,(11):1574.
 GAO Xuhang,ZHENG Yuqun,HE Zhijie,et al.Research progress on relationsship between gene polymorphism and diabetic nephropathy[J].,2019,(3):1574.
[6]张晓丽.血液透析联合血液灌注对糖尿病肾病患者血清空腹血糖、 C反应蛋白、白细胞介素6影响的临床研究[J].陕西医学杂志,2020,49(1):68.
 ZHANG Xiaoli..Effect of hemodialysis and blood perfusion on serum FPG,CRP and IL6 in patients with diabetic nephropathy[J].,2020,49(3):68.
[7]张 菁,姚 蔚,张进安,等.沙格列汀联合前列地尔治疗老年糖尿病肾病临床评价*[J].陕西医学杂志,2020,49(12):1657.[doi:DOI:10.3969/j.issn.1000-7377.2020.12.032]
 ZHANG Jing,YAO Wei,ZHANG Jin'an,et al.Clinical evaluation of saxagliptin combined with alprostadil in treatment of elderly diabetic nephropathy[J].,2020,49(3):1657.[doi:DOI:10.3969/j.issn.1000-7377.2020.12.032]
[8]刘海波,许建秦,李春梦,等.胱抑素C和甘油三酯检测对糖尿病肾病的早期诊断价值研究[J].陕西医学杂志,2021,50(1):96.[doi:DOI:10.3969/j.issn.1000-7377.2021.01.026]
 LIU Haibo,XU Jianqin,LI Chunmeng,et al.Value of cystatin C and triglyceride in early diagnosis of diabetic nephropathy[J].,2021,50(3):96.[doi:DOI:10.3969/j.issn.1000-7377.2021.01.026]
[9]袁 瑾,赵 灿,张渭涛.依普利酮通过靶向微小RNA-192和微小RNA-29a/b/c减轻糖尿病肾病模型大鼠肾损伤机制研究[J].陕西医学杂志,2022,51(3):293.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.007]
 YUAN Jin,ZHAO Can,ZHANG Weitao.Mechanism of eplerenone alleviating renal injury in diabetic nephropathy rat model by targeting miR-192 and miR-29a/b/c[J].,2022,51(3):293.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.007]
[10]张锦华,高 明,朱小静,等.促红细胞生成素对高糖诱导大鼠近端肾小管上皮细胞转分化的影响[J].陕西医学杂志,2022,51(10):1183.[doi:DOI:10.3969/j.issn.1000-7377.2022.10.002]
 ZHANG Jinhua,GAO Ming,ZHU Xiaojing,et al.Effect of EPO on transdifferentiation of rat proximal renal tubular epithelial cells induced by high glucose[J].,2022,51(3):1183.[doi:DOI:10.3969/j.issn.1000-7377.2022.10.002]

备注/Memo

备注/Memo:
基金项目:辽宁省大连市医学科学研究计划项目(1811011)
更新日期/Last Update: 2023-03-06