Molecular Mechanism of Tangshenping Capsule in Intervening Apoptosis of Podocytes Induced by High Glucose+LPS Through PI3K/Akt Signaling Pathway

Ying-chao WANG; Jing ZHAO; Zong-jiang ZHAO; Lei DU; Chen TIAN; Ling LI

doi:10.13422/j.cnki.syfjx.20190421

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Molecular Mechanism of Tangshenping Capsule in Intervening Apoptosis of Podocytes Induced by High Glucose+LPS Through PI3K/Akt Signaling Pathway

Pharmacology | 更新时间：2021-02-09

- Molecular Mechanism of Tangshenping Capsule in Intervening Apoptosis of Podocytes Induced by High Glucose+LPS Through PI3K/Akt Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 5, Pages: 105-111(2019)
- 作者机构：
  
  1.北京航天总医院，北京　 100007；
  2.北京中医药大学，北京　 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190421
  CLC： R22;R242;R2-031;R285.5;R273
- Received：04 July 2018，
  
  Published Online：05 November 2018，
  
  Published：05 March 2019
- 稿件说明：
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Ying-chao WANG, Jing ZHAO, Zong-jiang ZHAO, et al. Molecular Mechanism of Tangshenping Capsule in Intervening Apoptosis of Podocytes Induced by High Glucose+LPS Through PI3K/Akt Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 105-111.
DOI：

Ying-chao WANG, Jing ZHAO, Zong-jiang ZHAO, et al. Molecular Mechanism of Tangshenping Capsule in Intervening Apoptosis of Podocytes Induced by High Glucose+LPS Through PI3K/Akt Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 105-111. DOI： 10.13422/j.cnki.syfjx.20190421.

摘要

目的：

观察糖肾平对高糖环境下脂多糖(LPS)对足细胞凋亡的影响，并探讨其作用机制。

方法：

利用雄性Wistar大鼠，分别用糖肾平小、中、大剂量(0.525

1.05

2.1g·kg

－1

)，厄贝沙坦(17.5mg·kg

－1

)灌胃给药，制备相应药物血清。采用高糖，LPS体外刺激大鼠足细胞建立模型。并分为正常组（5%正常大鼠血清），高糖组（5%模型大鼠血清＋4.5‰葡萄糖），高糖＋LPS组（5%模型大鼠血清＋4.5‰葡萄糖＋LPS 1mg·L

－1

），厄贝沙坦组（5%厄贝沙坦组大鼠血清＋4.5‰葡萄糖＋LPS 1mg·L

－1

），糖肾平小剂量组（5%糖肾平小剂量大鼠血清＋4.5‰葡萄糖＋LPS 1mg·L

－1

），中剂量组（5%糖肾平中剂量大鼠血清＋4.5‰葡萄糖＋LPS 1mg·L

－1

），大剂量组（5%糖肾平大剂量大鼠血清＋4.5‰葡萄糖＋LPS 1mg·L

－1

）。采用蛋白免疫印迹法(Western blot)及逆转录聚合酶链式反应(RT-PCR)检测足细胞中CD2相关蛋白(CD2AP)，nephrin和磷脂酰肌醇3激酶／蛋白激酶B(PI3K/Akt)信号转导通路中关键因子的蛋白和mRNA的表达水平。

结果：

与正常组比较，高糖组和高糖＋LPS组足细胞nephrin

CD2AP

PI3K

Akt蛋白及mRNA表达明显减少(

0.05，

0.01)；B淋巴细胞瘤-2相关凋亡蛋白（Bad蛋白）及mRNA表达明显增加(

0.05，

0.01)。与高糖＋LPS组比较，厄贝沙坦组足细胞CD2AP

PI3K

Akt蛋白及mRNA表达明显增加(

0.05，

0.01)；nephrin mRNA表达增加；Bad蛋白及mRNA蛋白表达减少。糖肾平各组足细胞CD2AP

PI3K

Akt蛋白及mRNA表达明显增加(

0.05，

0.01)；Bad蛋白及mRNA蛋白表达减少(

0.05，

0.01)。

结论：

糖肾平维持足细胞裂孔隔膜蛋白稳定表达，保护肾小球滤过屏障，同时进一步激活PI3K/Akt信号通路，抑制足细胞凋亡；是其多靶点防治糖尿病肾病的作用机制之一。

Abstract

Objective:

To observe effect of Tangshenping capsule on lipopolysaccharide (LPS)-stimulated podocytes apoptosis under high glucose conditions of podocyte in rats with diabetic nephropathy (DN)

and discuss possible mechanism.

Method:

With cultured rat podocytes as object of study

the podocytes model was established with high glucose and LPS

and divided into 7 groups: control group

high glucose group

high glucose plus LPS group

irbesartan group

and low

moderate and high-dose Tangshenping capsule groups.Protein and mRNA expressions of CD2-associated protein (CD2AP)

nephrin

phosphatidylinositol 3-kinase (PI3K)

protein kinase B (Akt) and B-cell lymphoma-2 associated death protein (Bad protein) of podocyte in each group were detected by Western blot and reverse transcription polymerase chain reaction (RT-PCR).

Result:

Compared with control group

the protein and mRNA expressions of podocyte CD2AP

nephrin

PI3K

Akt decreased definitely (

0.05

0.01)

while Bad protein and mRNA expressions increased definitely (

0.05

0.01). Compared with high glucose plus LPS group

the protein and mRNA expressions of podocyte CD2AP

PI3K

Akt increased definitely (

0.05

0.01)

whereas Bad protein and mRNA expressions decreased definitely (

0.05

0.01) in irbesartan group. The protein and mRNA expressions of podocyte nephrin

CD2AP

PI3K

Akt increased definitely (

0.05

0.01)

and Bad protein and mRNA expressions decreased definitely (

0.05

0.01) in three Tangshenping capsule groups.

Conclusion:

Tangshenping capsule can maintain a stable protein expression of Slit diaphragm (SD) in podocyte

inhibit podocyte apoptosis by activating PI3K/Akt signaling pathway. This is one of mechanisms for preventing and treating diabetic nephropathy.

关键词

Keywords

references

HU L , Zaloudek C , Mills G B , et al . In vivo and in vitro ovariancarcinoma growth inhibition by a phosphatidylinositol 3 kinase in-hibitor (LY294002) [J]. Clin Cancer Res , 2009 , 6 ( 3 ): 880 - 886 .

Briasoni L , SchnPaer H W , Kopp J B. Advnaces in the biology and geneties of the podoeytopathies: implications for diangosis and therapy [J]. Arch Pathol Lab Med , 2009 , 133 ( 2 ): 201 - 216 .

CHUANG P Y , HE J C. Signaling in regulation of podocyte phenotypes [J]. Nephron Physiol , 2009 , 111 ( 2 ): 9 - 15 .

李敏州，高彦彬，马鸣飞，等．糖尿病肾病发病机制研究进展 [J]. 中国实验方剂学杂志， 2012 , 18 ( 22 ): 344 - 349 .

Vezrola D , Gandolof M T , Ferrario F , et al . Aopoptosis in the kidneys of patients with typeⅡ diabetic nephropathy [J]. Kidney Int , 2007 , 72 ( 10 ): 1262 - 1272 .

石格，毛志敏，万毅刚，等．糖尿病肾病足细胞损伤的病理机制及中药的干预作用 [J]. 中国中药杂志， 2016 , 41 ( 13 ): 2416 - 2421 .

ZHANG Z , PENG H , CHEN J , et al . MicroRNA-21 protects from mesangial cell proliferation induced by diabetic nephropathy in db/db mice [J]. FEBS Lett , 2009 , 583 ( 12 ): 2009 - 2014 .

朱海慧，叶学锋．中医药防治糖尿病肾病足细胞损伤研究进展 [J]. 辽宁中医药大学学报， 2014 , 16 ( 1 ): 109 - 111 .

LI X Z , CHUANG P Y , D'Agati V D , et al . Nephrin preserves podocyte viability and glomerular structure andfunction in adult kidneys [J]. J Am Soc Nephrol , 2015 , 26 ( 10 ): 2361 - 2377 .

赵宗江，王颖超，杜磊，等．健脾益肾化瘀通络方对糖尿病肾病大鼠氧化应激的影响 [J]. 北京中医药大学学报， 2013 , 36 ( 3 ): 161 - 165,218 .

杜磊，赵敬，赵宗江，等．糖肾平对高糖＋LPS刺激足细胞TGF- β 1 /Smad7信号转导通路影响的研究 [J]. 中国中西医结合肾病杂志， 2013 , 14 ( 2 ): 107 - 110 .

王颖超，赵宗江，赵敬，等．糖肾平对糖尿病肾病大鼠足细胞nephrin与CD2AP蛋白及其mRNA表达的影响 [J]. 中国中西医结合肾病杂志， 2014 , 15 ( 2 ): 107 - 109 .

王颖超，于眉，杨敏，等．糖肾平对糖尿病肾病大鼠 α -actinin-4表达及足细胞数目的影响 [J]. 辽宁中医药大学学报， 2018 , 20 ( 4 ): 31 - 35 .

王婷，赵宗江，张新雪，等．糖肾宁含药血清对高糖刺激肾小管上皮细胞增殖作用及RhoA/ROCK信号通路影响的实验研究 [J]. 世界科学技术—中医药现代化， 2017 , 19 ( 6 ): 1066 - 1071 .

Boddana P , Caskey F , Casula A , et al . UK renal registry 11 th annual report (December 2008)：chapter 14UK renal registry and international comparisons [J]. Nephron Clin Pract , 2009 , 111 ( Supp11 ): 269 - 276 .

Schernthaner G . Kidney disease in diabetology: lessons from 2010 [J]. Nephrol Dial Transplant , 2011 , 26 ( 2 ): 454 - 457 .

刘臻，张铭倩，朱虹．栝楼瞿麦汤对糖尿病肾病大鼠脂肪因子和足细胞nephrin的影响 [J]. 中国实验方剂学杂志， 2017 , 23 ( 23 ): 134 - 139 .

Kelly J C . China faces massive wave of diabetes-linked chronic diseases [J]. JAMA , 2013 , 310 : 916 - 917,948-958 .

Huber T B , Harfleben B , Kim J , et al . Nephrinand CD2AP associate with phosphoinositide 3-OH kinase an dstimulate Akt-dependent signaling [J]. Mol Cell Bio1 , 2003 , 23 ( 14 ): 4917 - 4928 .

LIX Z , HE J C. An update: the role of nephrin inside and outside the kidney [J]. Sci China: Life Sci , 2015 , 58 ( 7 ): 649 - 657 .

Beck J T , Ismail A , Tolomeo C. Targeting the phosphatidylinositol 3-kinase(PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway：an emerging treatment strategy for squamous cell lung carcinoma [J]. Cancer Treat Rev , 2014 , 40 ( 8 ): 980 - 989 .

Theodoropoulou M , Stalla G K. Somatostatin receptors: from signaling to clinical practice [J]. Front Neuroendoctrinol , 2013 , 34 ( 3 ): 228 - 252 .

Lopiccolo J , Blumenthal G M , Bernstein W B , et al . Targeting the PI3K/Akt/mTOR pathway：effective combinations and clinical considerations [J]. Drug Resist Update , 2007 , 11 ( 1/2 ): 32 - 50 .

WANG L S , GAI P Z , XU R G , et al . Shikonin protects chondrocytes from interleukin-1 beta-induced apoptosis by regulating PI3K/Akt signaling pathway [J]. Int J Clin Exp Pathol , 2015 , 8 ( 1 ): 298 - 308 .

Tokuhira N , Kitagishi Y , Suzuki M , et al . PI3K/Akt/PTEN pathway as a target for Crohn′s disease therapy(review) [J]. Int J Mol Med , 2015 , 35 ( 1 ): 10 - 16 .

贾鹏，陈盛业，甘宇，等．中医药治疗糖尿病肾病研究进展 [J]. 辽宁中医药大学学报， 2010 , 12 ( 7 ): 125 - 126 .

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