Mechanisms of Bushen Tongluo Jiangzhuo Prescription in Improving Renal Fibrosis in Rats with Chronic Kidney Disease Based on PI3K/Akt/mTOR Signaling Pathway

BAO Xincui; ZHAO Baosheng; QIN Lingling; WANG Haiyan; YANG Jing; WANG You; WU Lijia; LI Yujin; GAO Ming; LYU Cuiyan; LIU Tonghua

doi:10.13422/j.cnki.syfjx.20251436

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Mechanisms of Bushen Tongluo Jiangzhuo Prescription in Improving Renal Fibrosis in Rats with Chronic Kidney Disease Based on PI3K/Akt/mTOR Signaling Pathway

更新时间：2026-02-28

- Mechanisms of Bushen Tongluo Jiangzhuo Prescription in Improving Renal Fibrosis in Rats with Chronic Kidney Disease Based on PI3K/Akt/mTOR Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 6, Pages: 100-108(2026)
- 作者机构：
  
  1.北京中医药大学，北京 100029
  2.首都医科大学附属北京中医医院，北京 100010
  3.北京中医药大学附属东直门医院，北京 100007
  4.日本武库川女子大学，日本兵库县 663-8558
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20251436
  CLC： R282;R242;R259
- Received：06 May 2025，
  
  Revised：2025-06-20，
  
  Accepted：27 June 2025，
  
  Online First：11 July 2025，
  
  Published：20 March 2026
- 稿件说明：
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包新翠,赵保胜,秦灵灵等.基于PI3K/Akt/mTOR信号通路探讨补肾通络降浊方改善慢性肾脏病大鼠肾纤维化的作用机制[J].中国实验方剂学杂志,2026,32(06):100-108.

BAO Xincui,ZHAO Baosheng,QIN Lingling,et al.Mechanisms of Bushen Tongluo Jiangzhuo Prescription in Improving Renal Fibrosis in Rats with Chronic Kidney Disease Based on PI3K/Akt/mTOR Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(06):100-108.
包新翠,赵保胜,秦灵灵等.基于PI3K/Akt/mTOR信号通路探讨补肾通络降浊方改善慢性肾脏病大鼠肾纤维化的作用机制[J].中国实验方剂学杂志,2026,32(06):100-108. DOI： 10.13422/j.cnki.syfjx.20251436.

BAO Xincui,ZHAO Baosheng,QIN Lingling,et al.Mechanisms of Bushen Tongluo Jiangzhuo Prescription in Improving Renal Fibrosis in Rats with Chronic Kidney Disease Based on PI3K/Akt/mTOR Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(06):100-108. DOI： 10.13422/j.cnki.syfjx.20251436.

摘要

目的

探究补肾通络降浊方通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路改善慢性肾脏病（CKD）大鼠肾纤维化的作用机制。

方法

70只SPF级SD大鼠随机分为空白组15只及造模组55只，造模组大鼠予2.5%的腺嘌呤混悬液200 mg·kg

-1

·d

-1

灌胃4周制备CKD模型，将造模成功的大鼠随机分为模型组，厄贝沙坦组（20.25 mg·kg

-1

·d

-1

），补肾通络降浊方低、中、高剂量组（5.82、11.64、23.28 g·kg

-1

·d

-1

），每组10只，各组分别予等体积的生理盐水、相应浓度的厄贝沙坦和补肾通络降浊方灌胃12周。动态检测大鼠体质量及肾功能指标；采用全自动生化仪检测大鼠血肌酐（SCr）、血尿素氮（BUN）、尿白蛋白肌酐比（ACR）、24 h尿蛋白定量（24 hUTP）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、白细胞介素（IL）-1

、IL-6、肿瘤坏死因子-

（TNF-

）情况；苏木素-伊红（HE）染色和马松（Masson）染色观察肾脏组织病理变化；免疫组化法（IHC）检测大鼠PI3K、Akt、磷酸化（p）-Akt、mTOR的表达；蛋白免疫印迹法（Western blot）检测大鼠肾组织PI3K、p-Akt、Akt、p-mTOR、mTOR的蛋白表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠肾组织中PI3K、Akt、mTOR mRNA表达水平。

结果

与模型组比较，厄贝沙坦组及补肾通络降浊方低、中、高剂量组大鼠SCr、BUN、ACR、24 hUTP、IL-1

、IL-6、TNF-

均显著降低（

0.01），AST显著升高（

0.01），ALT差异无统计学意义；同时各给药组较模型组大鼠肾组织病理结果显示，肾小管上皮细胞水肿、坏死及肾小囊扩张减轻，肾组织炎症细胞浸润减少，肾间质及肾小球纤维化改善明显，以补肾通络降浊方高剂量组效果最佳。Real-time PCR结果显示，补肾通络降浊方高剂量组PI3K、Akt、mTOR的mRNA表达显著下调（

0.01）。IHC结果显示补肾通络降浊方高剂量组肾组织中PI3K、p-Akt表达水平显著降低（

0.01）。Western blot结果显示补肾通络降浊方高剂量组PI3K、p-Akt/Akt、p-mTOR/mTOR表达水平显著降低（

0.01）。

结论

补肾通络降浊方能改善CKD大鼠的肾功能指标，减少肾组织内胶原蛋白沉积，降低血清炎症因子水平，并通过下调PI3K/Akt/mTOR信号通路激活自噬，改善肾纤维化，保护肾功能。

Abstract

Objective

To investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway.

Methods

Seventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （

=15） and a modeling group （

=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg

-1

·d

-1

by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg

-1

·d

-1

）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg

-1

·d

-1

， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1

（IL-1

）， interleukin-6 （IL-6）， and tumor necrosis factor-

（TNF-

） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues.

Results

Compared with the model group， rats in the ir

besartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1

， IL-6， and TNF-

（

0.01）. AST levels were significantly increased （

0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （

0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （

0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （

0.01）.

Conclusion

Bushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

关键词

Keywords

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