[1]崔方强,江心灿,王悦芬,等.保肾通络方对糖尿病肾病小鼠肾小管间质纤维化及上皮细胞间充质转分化的影响[J].陕西中医,2024,(8):1011-1015,1025.[doi:DOI:10.3969/j.issn.1000-7369.2024.08.001]
 CUI Fangqiang,JIANG Xincan,WANG Yuefen,et al.Effect of Baoshen Tongluo decoction on renal tubular interstitial fibrosis and epithelial-mesenchymal transition in DN mice[J].,2024,(8):1011-1015,1025.[doi:DOI:10.3969/j.issn.1000-7369.2024.08.001]
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保肾通络方对糖尿病肾病小鼠肾小管间质纤维化及上皮细胞间充质转分化的影响
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2024年8期
页码:
1011-1015,1025
栏目:
基础研究
出版日期:
2024-08-05

文章信息/Info

Title:
Effect of Baoshen Tongluo decoction on renal tubular interstitial fibrosis and epithelial-mesenchymal transition in DN mice
作者:
崔方强江心灿王悦芬孟 元蔡 朕赵文景
(首都医科大学附属北京中医医院,北京 100010)
Author(s):
CUI FangqiangJIANG XincanWANG YuefenMENG YuanCAI ZhenZHAO Wenjing
(Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)
关键词:
糖尿病肾病 保肾通络方 益肾活血通络 肾小管上皮细胞 间充质转分化 间质纤维化
Keywords:
Diabetic nephropathy Baoshen Tongluo decoction Yishen Huoxue Tongluo Renal tubular epithelial cells Epithelial-mesenchymal transition Interstitial fibrosis
分类号:
R 587.2
DOI:
DOI:10.3969/j.issn.1000-7369.2024.08.001
文献标志码:
A
摘要:
目的:观察保肾通络方对糖尿病肾病(DN)小鼠肾小管间质纤维化及上皮细胞间充质转分化(EMT)的影响。方法:选用KK-Ay小鼠作为DN模型小鼠,随机分为模型组、保肾通络方组及缬沙坦组,正常对照组小鼠选用C57BL/6J小鼠。保肾通络方组小鼠给予保肾通络方灌胃治疗,缬沙坦组小鼠给予缬沙坦灌胃治疗,模型组、正常对照组小鼠给予剂量相同的蒸馏水灌胃治疗; 灌胃给药12周后检测各组血清肌酐、尿素氮水平,HE、PAS、Masson染色观察肾组织病理改变,同时进行细胞外基质蛋白Collagen Ⅰ、FN及肾小管EMT标志蛋白α-SMA、E-cadherin表达检测。结果:模型组小鼠血清肌酐、尿素氮水平较正常对照组明显升高(均P<0.05),保肾通络方组及缬沙坦组小鼠血清肌酐、尿素氮水平较模型组明显降低(均P<0.05)。与正常对照组相比,模型组小鼠肾小管出现明显的间质纤维化及上皮细胞脱落、空泡变性,而保肾通络方组及缬沙坦组小鼠上述病理改变均明显减轻。模型组小鼠肾小管Collagen Ⅰ、FN蛋白及mRNA表达较正常对照组明显上调(均P<0.05),保肾通络方组及缬沙坦组小鼠肾小管Collagen Ⅰ、FN蛋白及mRNA表达较模型组明显下调(均P<0.05)。与正常对照组相比,模型组小鼠肾小管上皮细胞α-SMA蛋白及mRNA表达明显上调,E-cadherin蛋白及mRNA表达明显下调(均P<0.05); 与模型组相比,保肾通络方组及缬沙坦组小鼠α-SMA蛋白及mRNA表达明显下调,E-cadherin蛋白及mRNA表达明显上调(均P<0.05)。结论:保肾通络方能够改善DN小鼠肾小管间质纤维化,减轻肾小管EMT。
Abstract:
Objective:To observe the effect of Baoshen Tongluo decoction on renal tubular interstitial fibrosis and epithelial-mesenchymal transition in DN mice.Methods:The model KK-Ay mice were separated into DN group,XST group and BSTL group randomly.C57BL/6J mice performed for NC group.Mice in BSTL group were given BSTL.Mice in XST group were given XST.Mice in DN and NC group were given distilled water.All mice were successive administration for 12 weeks.Serum creatinine,urea nitrogen and 24 h urine protein was detected.Renal tubular interstitial fibrosis was detected by HE,PAS and Masson staining.Immunohistochemistry and RT-PCR were used for detecting Collagen Ⅰ,FN,α-SMA and E-cadherin protein and mRNA expression.Results:Serum creatinine and urea nitrogen levels of mice in DN group were significantly higher than those in NC group(all P<0.05),while serum creatinine and urea nitrogen levels of mice in BSTL group and XST group were significantly lower than those in DN group(all P<0.05).Compared with NC group,the renal tubules in the DN group showed obvious interstitial fibrosis,epithelial cell exfoliation and vacuolar degeneration,while the above pathological changes were significantly reduced in BSTL group and XST group.The expression of Collagen Ⅰ and FN protein and mRNA in renal tubules of mice in DN group were significantly up-regulated compared with those in NC group(all P<0.05),while the expression of Collagen Ⅰ and FN protein and mRNA in renal tubules of mice in BSTL group and XST group were significantly down-regulated compared with those in DN group(all P<0.05).Compared with NC group,the expression of α-SMA protein and mRNA in renal tubular epithelial cells in DN group was significantly up-regulated,and the expression of E-cadherin protein and mRNA was significantly down-regulated(all P<0.05).Compared with DN group,α-SMA protein and mRNA expression in BSTL group and XST group were significantly down-regulated,while E-cadherin protein and mRNA expression were significantly up-regulated(all P<0.05).Conclusion:Baoshen Tongluo decoction can alleviate proteinuria and ameliorate renal function of DN,which partially through decreasing renal tubule interstitial fibrosis and epithelial-mesenchymal transition in DN.

参考文献/References:

[1] LIN Y C,CHANG Y H,YANG S Y,et al.Update of pathophysiology and management of diabetic kidney disease[J].J Formos Med Assoc,2018,117(8):662-675.
[2] REIDY K,KANG H M,HOSTETTER T,et al.Molecular mechanisms of diabetic kidney disease[J].J Clin Invest,2014,124(6):2333-2340.
[3] SLYNE J,SLATTERY C,MCMORROW T,et al.New developments concerning the proximal tubule in diabetic nephropathy:In vitro models and mechanisms[J].Nephrol Dial Transplant,2015,30(S4):60-67.
[4] ZENI L,NORDEN A G W,CANCARINI G,et al.A more tubulocentric view of diabetic kidney disease [J].J Nephrol,2017,30(6):701-717.
[5] LOEFFLER I,WOLF G.Epithelial-to-mesenchymal transition in diabetic nephropathy:Fact or fiction?[J].Cells,2015,4(4):631-652.
[6] VENKOV C D,LINK A J,JENNINGS J L,et al.A proximal activator of transcription in epithelial-mesenchymal transition [J].J Clin Invest,2007,117(2):482-491.
[7] FU H,LIU S,BASTACKY S I,et al.Diabetic kidney diseases revisited:A new perspective for a new era[J].Mol Metab,2019,30:250-263.
[8] 葛恺,李春梦,白妮,等.尿白蛋白/肌酐比、尿α1-微球蛋白、尿转铁蛋白联合检测对早期糖尿病肾病的诊断价值[J].陕西医学杂志,2022,51(12):1536-1539.
[9] QI C,MAO X,ZHANG Z,et al.Classification and differential diagnosis of diabetic nephropathy[J].J Diabetes Res,2017,2017:8637138.
[10] RUSSO L M,SANDOVAL R M,CAMPOS S B,et al.Impaired tubular uptake explains albuminuria in early diabetic nephropathy[J].J Am Soc Nephrol,2009,20(3):489-494.
[11] 宇汝翠,陆智慧,李金虎,等.益气养阴通络方通过lncRNA UCA1靶向调控miR-485-5p抑制糖尿病肾病大鼠肾小管上皮细胞凋亡及炎症反应作用机制[J].陕西中医,2023,44(8):1000-1004.
[12] 占志朋,谢席胜.肾小管损伤在糖尿病肾病发病机制中的作用研究进展[J].中国中西医结合肾病杂志,2021,22(3):277-279.
[13] DU L,QIAN X,LI Y,et al.Sirt1 inhibits renal tubular cell epithelial-mesenchymal transition through YY1 deacetylation in diabetic nephropathy[J].Acta Pharmacol Sin,2021,42(2):242-251.
[14] YANG Y,WANG Y,HE Z,et al.Trimetazidine inhibits renal tubular epithelial cells to mesenchymal transition in diabetic rats via upregulation of sirt1[J].Front Pharmacol,2020,11:1136.
[15] FRAGIADAKI M,MASON R M.Epithelial-mesenchymal transition in renal fibrosis-evidence for and against[J].Int J Exp Pathol,2011,92(3):143-150.
[16] 夏璁,叶晴晴,杨利利,等.消瘀泄浊饮对单侧输尿管梗阻大鼠肾小管上皮-间质转分化及PAR-3表达的影响[J].浙江中医药大学学报,2021,45(12):1343-1350.
[17] KALLURI R,NEILSON E G.Epithelial-mesenchymal transition and its implications for fibrosis[J].J Clin Invest,2003,112(12):1776-1784.
[18] ZEISBERG M,KALLURI R.The role of epithelial-to-mesenchymal transition in renal fibrosis[J].J Mol Med(Berl),2004,82(3):175-181.
[19] 黎艳,刘莉,王琪文,等.槲皮素对小鼠单侧输尿管结扎致肾间质纤维化的改善作用及机制研究[J].陕西医学杂志,2023,52(11):1473-1477,1482.
[20] 张执中,魏希锋,方兵,等.miR-150-5p缓解肾小管上皮细胞-间质转化及纤维化的作用机制探讨[J].宁夏医学杂志,2023,45(3):197-200.
[21] 张达江,王亮.Ⅰ型胶原蛋白的结构、功能及其应用研究的现状与前景[J].生物技术通讯,2006,18(2):265-269.
[22] GONG W,LI J,CHEN Z,et al.Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating CKIP-1 to resist HG-induced up-regulation of FN and ICAM-1 in GMCs and diabetic mice kidneys[J].Free Radic Biol Med,2017,106:393-405.
[23] 李凡,王杰,崔成姬,等.基于“脾病下流乘肾”探讨糖尿病肾病研究进展[J].陕西中医,2023,44(12):1823-1826.
[24] 李红典,董少宁,刘亚燊,等.补肾活血法治疗糖尿病肾病Ⅲ、Ⅳ期患者临床疗效观察[J].中华中医药杂志,2023,38(10):5105-5108.
[25] 崔方强,赵文景,王悦芬,等.“保肾通络方”联合基础治疗方案干预糖尿病肾病气阴两虚兼血瘀证44例临床研究[J].江苏中医药,2021,53(6):46-49.
[26] 崔方强,王悦芬,孟元,等.保肾通络方含药血清对高糖培养足细胞Nephrin、Desmin蛋白表达及细胞凋亡的影响[J].陕西中医,2023,44(8):995-999.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81703989); 北京市自然科学基金资助项目(7222271); 首都医科大学科研培育基金资助项目(PYZ22163)
更新日期/Last Update: 2024-08-08