糖肾平胶囊通过PI3K/Akt信号通路干预高糖＋LPS诱导足细胞凋亡的机制

王颖超; 赵敬; 赵宗江; 杜磊; 田晨; 李玲

doi:10.13422/j.cnki.syfjx.20190421

您当前的位置：

首页 >

文章列表页 >

糖肾平胶囊通过PI3K/Akt信号通路干预高糖＋LPS诱导足细胞凋亡的机制

药理 | 更新时间：2021-02-09

- 糖肾平胶囊通过PI3K/Akt信号通路干预高糖＋LPS诱导足细胞凋亡的机制
- Molecular Mechanism of Tangshenping Capsule in Intervening Apoptosis of Podocytes Induced by High Glucose+LPS Through PI3K/Akt Signaling Pathway
- 中国实验方剂学杂志 2019年25卷第5期页码：105-111
- 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：
  
  王颖超，硕士，主治医师，从事中医内科学研究，Tel: 010-63472524，E-mail: wangyingchaobear@sina.com
  李玲，硕士，副主任医师，从事中医内科学研究，Tel：010-63472524，E-mail: yj_zhi@126.com
- 基金信息：
  
  国家自然科学基金项目(30973831;81373831)
- DOI：10.13422/j.cnki.syfjx.20190421
  中图分类号： R22;R242;R2-031;R285.5;R273
- 收稿日期：2018-07-04，
  
  网络出版日期：2018-11-05，
  
  纸质出版日期：2019-03-05
- 稿件说明：
移动端阅览
王颖超, 赵敬, 赵宗江, 等. 糖肾平胶囊通过PI3K/Akt信号通路干预高糖＋LPS诱导足细胞凋亡的机制[J]. 中国实验方剂学杂志, 2019,25(5):105-111.

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.
王颖超, 赵敬, 赵宗江, 等. 糖肾平胶囊通过PI3K/Akt信号通路干预高糖＋LPS诱导足细胞凋亡的机制[J]. 中国实验方剂学杂志, 2019,25(5):105-111. DOI： 10.13422/j.cnki.syfjx.20190421.

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 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

石斛合剂含药血清对高糖诱导小鼠足细胞损伤的保护作用

足细胞自噬与糖尿病肾病的关系及中医药调控研究进展

糖肾平胶囊对糖尿病肾病大鼠肾脏保护作用及其对肾组织单核细胞趋化因子-1蛋白及mRNA表达的影响

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