糖肾平胶囊对糖尿病肾病KKAy小鼠肾脏保护作用及对Wnt/<italic style="font-style: italic">β</italic>-catenin信号通路的影响

蔡京娩; 赵宗江; 张新雪; 苗永辉; 王婷; 葛东宇; 宋璐霞

doi:10.13422/j.cnki.syfjx.20151522

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糖肾平胶囊对糖尿病肾病KKAy小鼠肾脏保护作用及对Wnt/β-catenin信号通路的影响

药理 | 更新时间：2021-02-09

- 糖肾平胶囊对糖尿病肾病KKAy小鼠肾脏保护作用及对Wnt/β-catenin信号通路的影响
- Renal Protective Effect of Tangshiping Capsule on Diabetic Nephropathy Kkay Mice and Its Effect on Wnt/β-catenin Signal Transduction Pathway
- 中国实验方剂学杂志 2019年25卷第15期页码：96-102
- 作者机构：
  
  北京中医药大学　中医学院，北京　 100029
- 作者简介：
  
  蔡京娩，在读硕士，从事中医药防治糖尿病肾病的机制研究，E-mail：1020209799@qq.com
  赵宗江，博士，教授，从事中医药防治糖尿病肾病的机制研究，E-mail：zongjiangz@ sina.com
- 基金信息：
  
  国家重点研发计划课题项目(2018YFC1704304);国家重点研发计划课题项目(2018YFC1704304);国家自然科学基金面上项目(81373831)
- DOI：10.13422/j.cnki.syfjx.20151522
  中图分类号： R22; R242; R2-031; R285
- 收稿日期：2019-03-25，
  
  网络出版日期：2019-04-18，
  
  纸质出版日期：2019-08-05
- 稿件说明：
移动端阅览
蔡京娩, 赵宗江, 张新雪, 等. 糖肾平胶囊对糖尿病肾病KKAy小鼠肾脏保护作用及对Wnt/β-catenin信号通路的影响[J]. 中国实验方剂学杂志, 2019,25(15):96-102.

Jing-mian CAI, Zong-jiang ZHAO, Xin-xue ZHANG, et al. Renal Protective Effect of Tangshiping Capsule on Diabetic Nephropathy Kkay Mice and Its Effect on Wnt/β-catenin Signal Transduction Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 96-102.
蔡京娩, 赵宗江, 张新雪, 等. 糖肾平胶囊对糖尿病肾病KKAy小鼠肾脏保护作用及对Wnt/β-catenin信号通路的影响[J]. 中国实验方剂学杂志, 2019,25(15):96-102. DOI： 10.13422/j.cnki.syfjx.20151522.

Jing-mian CAI, Zong-jiang ZHAO, Xin-xue ZHANG, et al. Renal Protective Effect of Tangshiping Capsule on Diabetic Nephropathy Kkay Mice and Its Effect on Wnt/β-catenin Signal Transduction Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 96-102. DOI： 10.13422/j.cnki.syfjx.20151522.

摘要

目的：

探讨糖肾平胶囊(糖肾平)对糖尿病肾病(DN)KKAy小鼠肾脏保护作用及其对Wnt/

-连环蛋白(

-catenin)途径信号通路的影响。

方法：

雌性10周龄SPF级KKAy小鼠60只，用KKAy鼠料诱导10周，以血糖

16.7 mmol·L

－1

，24 h尿蛋白

0.4 mg确定DN小鼠模型成功。将成模小鼠随机分为模型组、厄贝沙坦组、糖肾平小、中、大剂量(0.525，1.05，2.1 g·kg

－1

)组，10只雌性C57BL/6J小鼠作为正常组。每个治疗组均相应的治疗药物进行灌胃，正常组、模型组小鼠给予等体积的去离子水灌胃，灌胃剂量按0.01 mL·g

－1

体质量系数，每天1次。观察小鼠一般情况，每4周称体质量并测24 h尿蛋白定量。第26周，眼球取血并处死小鼠，并测量肾脏的质量，分离血清测中血尿素氮(BUN)，血肌酐(SCr)，甘油三酯(TG)，丙二醛(MDA)，一氧化氮(NO)和超氧化物歧化酶(SOD)的含量；用原位杂交、免疫组化检测肾组织Wnt4，糖原合成酶激酶3

(GSK3

)，

-连环蛋白(

-catenin)mRNA及蛋白的表达。

结果：

与模型组比较，糖肾平高剂量组体质量、肾重/体质量，24 h尿蛋白显著降低(

0.01)；肾脏病理损害明显减轻，血清BUN，SCr，TG和MDA含量显著降低(

0.01)，NO，SOD含量显著升高(

0.01)，Wnt4，Gsk-3

，

-catenin mRNA及蛋白表达显著减少(

0.01)。

结论：

糖肾平可能是通过抑制Wnt/

-catenin信号通路活化，逆转DN KKAy小鼠肾小管上皮细胞转分化，延缓肾间质纤维化的进程，进而发挥肾脏保护作用。

Abstract

Objective:

To investigate the renal protective effect of Tangshenping capsule (Tangshenping) on diabetic nephropathy (DN) KKAy mice and its effect on Wnt/

-catenin signaling pathway.

Method:

Sixty female Sprague-Dawley KKAy mice aged 10 weeks old were induced with KKAy rat feed for 10 weeks. The DN animal model was successfully determined with blood glucose (

16.7 mmol·L

-1

) and 24 hour urine protein (

0.4 mg). The model mice were randomly divided into a model group

an irbesartan group

and low

medium and high-dose Tangshenping group

with 10 female C57BL/6J mice as a control group. The treatment groups were given the corresponding drugs by gavage. The normal group and the model group were given an equal volume of deionized water by gavage. The intragastric dose was 0.01 mL·g

-1

body weight coefficient once a day. The general conditions of the mice were observed

the body mass was weighed every 4 weeks

and 24 h urine protein was quantified. At the 26

week

the blood was collected from eyeballs

and the mice were put to death. The quality of the kidneys

serum blood urea nitrogen (BUN)

serum creatinine (SCr)

triglyceride (TG)

malondialdehyde (MDA)

nitric oxide (NO) and superoxide dismutase (SOD) content were measured. In situ hybridization and immunohistochemistry were used to detect the expressions of Wnt4

glycogen synthase kinase 3

(GSK3

) and

-catenin in kidney tissues.

Result:

Compared with model group

body mass

kidney mass/body mass

and 24 h urine protein were significantly lower in high-dose Tangshenping group (

0.01). The pathological damage of the kidney was significantly reduced

the serum BUN

SCr

TG and MDA contents were significantly decreased (

0.01)

the contents of NO and SOD were significantly increased (

0.01)

and the protein and mRNA expression levels of Wnt4

Gsk-3

and

-catenin were decreased (

0.01).

Conclusion:

Tangshenping may inhibit the activation of Wnt/

-catenin signaling pathway

reverse the transdifferentiation of renal tubular epithelial cells in DN KKAy mice

delay the progression of renal interstitial fibrosis

and then exert renal protection.

关键词

Keywords

references

LIU Y , SONG Y , TAO L , et al . Prevalence of diabetic retinopathy among 13473 patients with diabetes mellitus in China: a cross-sectional epidemiological survey in six provinces [J]. BMJ Open , 2017 , 7 ( 1 ): e013199 .

JIA W , TONG N . Diabetes prevention and continuing health-care reform in China [J]. Lancet Diabetes Endo , 2015 , 3 ( 11 ): 840 - 842 .

ZUO H , SHI Z , Hussain A . Prevalence, trends and risk factors for the diabetes epidemic in China: a systematic review and Meta-analysis [J]. Diabetes Res Clin Pract , 2014 , 104 ( 3 ): 63 - 72 .

Završnik M , Letonja J , Makuc J , et al . Interleukin-4 gene (IL4) polymorphism rs2243250 isnot associated with diabetic nephropathy (DN) in Caucasians with type 2 diabetes mellitus (T2DM) [J]. Bosn J Basic Med Sci , 2018 , 7 . doi: 10.17305 http://doi.org/10.17305 .

ZHONG F , CHEN H , XIE Y , et al . Protein S protects against podocyte injury in diabetic nephropathy [J]. J Am Soc Nephrol , 2018 , doi: 10.1681/ASN.2017030234 http://doi.org/10.1681/ASN.2017030234 .

Donate-Correa J , Martín-Núñez E , Muros-de-Fuentes M , et al . Inflammatory cytokinesin diabetic nephropathy [J]. J Diabetes Res , 2015 , doi: 10.1155/2015/948417 http://doi.org/10.1155/2015/948417 .

Arora M K , Sarup Y , Tomar R , et al . Amelioration of diabetes-induced diabetic nephropathyby aloe vera: implication of oxidative stress and hyperlipidemia [J]. J Diet Suppl , 2018 , 5 : 1 - 18 .

Taghizadeh M , Soleimani A , Bahmani F , et al . Metabolic response to mulberry extract supplementation in patients with diabetic nephropathy: a randomized controlled trial [J]. Iran J Kidney Dis , 2017 , 11 ( 6 ): 438 - 446 .

HUANG J , LI J , CHEN Z , et al . Sphingosine kinase 1 mediates diabetic renal fibrosis via NF-κB signaling pathway: involvement of CK2α [J]. Oncotarget , 2017 , 8 ( 51 ): 88988 - 89004 .

Kinashi H , Falke L L , Nguyen T Q , et al . Connective tissue growth factor regulatesfibrosis-associated renal lymphangiogenesis [J]. Kidney Int , 2017 , 92 ( 4 ): 850 - 863 .

Šeruga M , Kariž S , Makuc J , et al . Endothelin-1 gene polymorphisms rs5370, rs1476046, and rs3087459 are not associated with diabetic nephropathy in caucasians with type2 diabetes mellitus [J]. Folia Med: Plovdiv , 2017 , 59 ( 3 ): 261 - 269 .

XU XH , DING D F , YONG H J , et al . Resveratrol transcriptionally regulates miRNA-18a-5pexpression ameliorating diabetic nephropathy via increasing autophagy [J]. Eur Rev MedPharmacol Sci , 2017 , 21 ( 21 ): 4952 - 4965 .

马海建，巫冠中．糖尿病肾病发病分子机制 [J]．现代生物医学进展， 2014 ， 14 ( 16 )： 3184 - 3187 ．

苗永辉，赵宗江，张新雪，等．糖尿病肾病“肾痿”学说的建立与阐释 [J]．世界科学技术—中医药现代化， 2017 ， 19 ( 6 )： 1031 - 1037 ．

王之琳，赵宗江．赵宗江教授治疗糖尿病肾病的学术思想及临床经验撷英 [J]．世界科学技术—中医药现代化， 2015 ， 17 ( 10 )： 2162 - 2166 ．

吴阿敏，赵宗江，张新雪，等．糖肾平对糖尿病肾病KK-Ay小鼠肾脏保护作用及对TGF-β1/Samd6/BMP7信号通路影响的研究 [J]．世界科学技术—中医药现代化， 2016 ， 18 ( 8 )： 1342 - 1352 ．

苗永辉．糖肾平对糖尿病肾病KKAy小鼠肾脏保护作用及RhoA/ROCK信号转导通路影响的研究 [D]．北京：北京中医药大学， 2017 ．

杨冠男．糖肾平对糖尿病肾病KKAy小鼠肾脏保护作用及Notch/snail1信号转导通路影响的研究 [D]．北京：北京中医药大学， 2017 ．

张新雪，张学凯，赵宗江，等． Rg1 Rb1对糖尿病大鼠肾组织结缔组织生长因子的影响 [J]．山东中医药大学学报， 2008 ， 23 ( 3 )： 203 - 233 ．

杨冠男，赵宗江，张新雪，等．糖肾宁对糖尿病肾病KKAy小鼠的肾脏保护作用及其对Notch/Snail1信号转导通路的影响 [J]．世界科学技术—中医药现代化， 2017 ， 19 ( 6 )： 183 - 191 ．

CHEN Z , XIE X , HUANG J , et al . Connexin43 regulates high glucose-induced expression of fibronectin, ICAM-1 and TGF-beta1via Nrf2/ARE pathway in glomerular mesangial cells [J]. Free Radic Biol Med , 2017 , 102 : 77 - 86 .

Blacklock C L , Hirst J A , Taylor K S , et al . Evidence fora dose effect of renin-angiotensin system inhibition onprogression of microalbuminuria in type 2 diabetes: a Meta-analysis [J]. Diabet Med , 2011 , 28 ( 10 ): 1182 .

Kohan D E , Pritchett Y , Molitch M , et al . Addition of at-rasentan to renin-angiotensin system blockade reducesalbuminuria in diabetic nephropathy [J]. J Am Soc Nephrol , 2011 , 22 ( 4 ): 763 .

邵义文，严群，超朱媛．中药对糖尿病并发症的治疗现状 [J]．广东药学院学报， 2009 ， 25 ( 1 )： 108 - 110 ．

苗永辉，赵宗江，张新雪．等糖尿病肾病“肾痿”学说的建立与阐释 [J]．世界科学技术—中医药现代化， 2017 ， 19 ( 6 )： 157 - 163 ．

刘微，李冀，盛波，等．胰岛素抵抗动物模型的研究进展 [J]．中医药信息， 2008 ， 2 ( 6 )： 9 - 11 ．

陈薇，宇李，双蕾，谢婧，等． 2型糖尿病KKAY小鼠动物模型的研究进展 [J]．临床医药文献杂志， 2017 ( 54 )： 195 - 196 ．

Khan A H , Capilla E , Hou J C , et al . Entry of newly synthesized GLUT4 into the insulin responsive storage compartment is dependent upon both the amino terminus and the large cytoplasmic loop [J]. J Biol Chem , 2004 , 279 ( 36 ): 37505 - 37511 .

闫喆，姚芳，杨林，等． Wnt/βcatenin信号途径在糖尿病肾病患者病患者肾小管间质损伤中的作用 [J]．临床与实验病理学杂志， 2018 ， 34 ( 7 )： 719 - 723 ．

Nusse R , Clevers H . Wnt/β-catenin signaling, disease, and emer-ging therapeutic modalities [J]. Cell , 2017 , 169 ( 6 ): 985 .

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Renal Protective Effect of Tangshiping Capsule on Diabetic Nephropathy Kkay Mice and Its Effect on Wnt/β-catenin Signal Transduction Pathway

DOI：10.13422/j.cnki.syfjx.20151522

摘要

Abstract

关键词

Keywords

references