Effect of Modified Shengjiangsan Influences on PI3K/Akt/mTOR Signaling Pathway and Autophagy in Rats with Membranous Nephropathy

Fei GAO; Ze-ze WANG; Bing YANG; Jin-chuan TAN

doi:10.13422/j.cnki.syfjx.20202040

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Effect of Modified Shengjiangsan Influences on PI3K/Akt/mTOR Signaling Pathway and Autophagy in Rats with Membranous Nephropathy

Classic Prescriptions | 更新时间：2020-09-16

- Effect of Modified Shengjiangsan Influences on PI3K/Akt/mTOR Signaling Pathway and Autophagy in Rats with Membranous Nephropathy
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 20, Pages: 25-31(2020)
- 作者机构：
  
  1.河北中医学院，石家庄 050200
  2.河北省中医院，石家庄 050011
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202040
  CLC： R2-0;R289;R692
- Received：14 May 2020，
  
  Published Online：13 August 2020，
  
  Published：20 October 2020
- 稿件说明：
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高飞,王泽泽,杨冰等.加味升降散对膜性肾病大鼠PI3K/Akt/mTOR信号通路及自噬的影响[J].中国实验方剂学杂志,2020,26(20):25-31.

GAO Fei,WANG Ze-ze,YANG Bing,et al.Effect of Modified Shengjiangsan Influences on PI3K/Akt/mTOR Signaling Pathway and Autophagy in Rats with Membranous Nephropathy[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(20):25-31.
高飞,王泽泽,杨冰等.加味升降散对膜性肾病大鼠PI3K/Akt/mTOR信号通路及自噬的影响[J].中国实验方剂学杂志,2020,26(20):25-31. DOI： 10.13422/j.cnki.syfjx.20202040.

GAO Fei,WANG Ze-ze,YANG Bing,et al.Effect of Modified Shengjiangsan Influences on PI3K/Akt/mTOR Signaling Pathway and Autophagy in Rats with Membranous Nephropathy[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(20):25-31. DOI： 10.13422/j.cnki.syfjx.20202040.

摘要

目的

探讨加味升降散对膜性肾病(MN)大鼠的干预作用及相关作用机制。

方法

采用大鼠尾静脉注射阳离子化牛血清白蛋白(C-BSA)的方法建立MN大鼠模型。设正常组、模型组、加味升降散组（27.3 g·kg

-1

）和贝那普利组（10 mg·kg

-1

），分别给予相应剂量药物灌胃，每日1次，连续干预4周。给药结束后检测大鼠24 h尿蛋白（UTP）水平，血清总胆固醇(TC)，甘油三酯(TG)，总蛋白(TP)，白蛋白(Alb)，肌酐(SCr)，尿素氮(BUN)水平；马松（Masson）染色、碘酸六胺银（PASM）染色及透射电镜观察大鼠肾脏病理学变化；免疫荧光观察大鼠肾脏免疫球蛋白（Ig）G沉积；蛋白免疫印迹法（Western blot）检测磷脂酰肌醇-3激酶/蛋白激酶B/雷帕霉素靶蛋白（PI3K/Akt/mTOR）信号通路相关分子及自噬相关指标LC3和Beclin1的表达水平。

结果

与正常组比较，模型组大鼠UTP，血清中TC，TG水平均升高，TP，Alb水平明显降低（

0.05）；肾小球增大，基底膜出现不同程度的增厚和空泡变性，嗜复红蛋白沉积，肾小球毛细血管袢IgG弥漫性沉积，上皮下可见大小不等的电子致密物沉积，足细胞足突广泛融合；磷酸化（p）-PI3K，p-Akt和p-mTOR蛋白表达均明显增加（

0.05），自噬标志蛋白LC3和Beclin1蛋白表达量均明显下降（

0.05）；与模型组比较，加味升降散组和贝那普利组大鼠UTP，血清中TC，TG水平均有不同程度的下降，TP，Alb水平有不同程度的升高(

0.05)；大鼠肾组织病理损伤均有所减轻；p-PI3K，p-Akt和p-mTOR蛋白表达量明显下降（

0.05）；自噬标志蛋白LC3和Beclin1蛋白表达量明显升高（

0.05）。

结论

加味升降散可通过减少尿蛋白，减轻肾脏病理损伤，延缓疾病进展，其作用与抑制PI3K/Akt/mTOR信号通路和激活肾脏自噬有关。

Abstract

Objective

To explore the intervention effect of modified Shengjiangsan in rats with membranous nephropathy (MN) and its related mechanism.

Method

Rats were injected with cationized bovine serum Albumin (C-BSA) in the tail vein to establish a rat model of membranous nephropathy. The normal group

model group

modified Shengjiangsan group (27.3 g·kg

-1

) and benazepril group (10 mg·kg

-1

) were established in this study. Each group was given corresponding dosage of the drug once a day for 4 weeks of continuous intervention. After the administration

the levels of 24-hour urine protein (UTP)

total cholesterol (TC)

triglyceride (TG)

total protein (TP)

Albumin (Alb)

creatinine (SCr)

urea nitrogen (BUN) level was detected. we observed the pathological changes of rat kidneys by the technology of Masson staining

silver hexylamine iodate (PASM) staining and transmission electron microscopy. immunofluorescence technology was used to detect immunoglobulin （Ig）G deposition in rat kidneys. Western blot was used to detect the expression levels of key proteins in phosphatidylinositol 3-kinase/proline protein kinase B/rapamycin target protein (PI3K/Akt/mTOR) signaling pathway and autophagy marker proteins LC3 and Beclin1.

Result

Compared with normal group

the UTP

serum TC and TG levels were significantly increased

TP and Alb levels were significantly reduced in model group(

0.05). We detected the kidney pathological changes include of glomerulus enlargement

basement membrane thickening

vacuolar degeneration

pheotropin deposition

glomerular capillary loop IgG diffuse deposition

electron dense deposits of varying sizes and podocytes under the epithelium extensive integration of foot processes， the expression of p-PI3K

p-Akt and p-mTOR protein was significantly increased (

0.05). The expression of autophagy marker proteins LC3 and Beclin1 protein decreased significantly(

0.05). Compared with model group

the UTP

serum TC and TG levels were decreased in the benazepril group and modified Shengjiangsan group

and the TP and Alb levels were increased (

0.05)， the histopathological changes of rat kidney were all reduced， the expression of p-PI3K

p-Akt and p-mTOR protein was significantly reduced(

0.05)， autophagy marker proteins LC3 and Beclin1 protein expression were significantly increased.

Conclusion

Modified Shengjiangsan can reduce urinary protein

reduce kidney pathological damage and delay disease progression

which is related to its inhibition of PI3K/Akt/mTOR signaling pathway and activation of renal autophagy.

关键词

Keywords

references

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