Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3<italic style="font-style: italic">β</italic> Signaling Pathway

GAO Jiaxin; WANG Jianbo; XUE Yanan; SUN Jie; WANG Dan; HAN Kun; ZHANG Yunyu; YIN Yiran; FENG Xiaofan

doi:10.13422/j.cnki.syfjx.20231163

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Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway

更新时间：2023-12-28

- Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 30, Issue 3, Pages: 10-17(2024)
- 作者机构：
  
  辽宁中医药大学中西医结合学院，中医脏象理论及应用教育部重点实验室，沈阳 110847
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20231163
  CLC： R22;R28;R96;R587.1
- Received：10 March 2023，
  
  Published Online：08 June 2023，
  
  Published：05 February 2024
- 稿件说明：
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高佳馨,王建波,薛亚楠等.基于PI3K/Akt/GSK-3β信号通路探讨七味白术散对糖尿病脑病大鼠认知功能障碍的影响[J].中国实验方剂学杂志,2024,30(03):10-17.

GAO Jiaxin,WANG Jianbo,XUE Yanan,et al.Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(03):10-17.
高佳馨,王建波,薛亚楠等.基于PI3K/Akt/GSK-3β信号通路探讨七味白术散对糖尿病脑病大鼠认知功能障碍的影响[J].中国实验方剂学杂志,2024,30(03):10-17. DOI： 10.13422/j.cnki.syfjx.20231163.

GAO Jiaxin,WANG Jianbo,XUE Yanan,et al.Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(03):10-17. DOI： 10.13422/j.cnki.syfjx.20231163.

摘要

目的

观察七味白术散对糖尿病脑病（DE）大鼠模型的治疗作用，基于磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/糖原合成酶激酶-3

（GSK-3

）通路探究其可能存在的机制。

方法

选取SPF级雄性Wistar大鼠48只，随机分为空白组8只、高脂饲料组40只。高脂饲料组大鼠喂养12周后，连续2 d腹腔注射35 mg·kg

-1

的1%链脲佐菌素构建DE模型，空白组大鼠注射等量柠檬酸钠缓冲液。造模成功后，按血糖和体质量随机分为模型组、七味白术散低、中、高剂量组（3.15、6.3、12.6 g·kg

-1

）、联合西药组（二甲双胍+罗格列酮，0.21 g·kg

-1

），每组各6只。给药组灌胃给予相应剂量药物，空白组和模型组灌胃等体积生理盐水，1次/d，连续给药6周。采用Morris水迷宫检测DE大鼠空间记忆能力，酶联免疫吸附测定法（ELISA）检测空腹胰岛素（FINS）水平并计算胰岛素抵抗指数（HOMA-IR），苏木素-伊红（HE）染色观察大鼠海马组织病理变化，ELISA检测海马组织氧化应激指标，实时荧光定量聚合酶链式反应（Real-time PCR）检测海马组织PI3K、Akt、核转录因子-

B（NF-

B）、肿瘤坏死因子-

（TNF-

）、和白细胞介素-1

（IL-1

）mRNA表达，蛋白免疫印迹法（Western blot）检测大鼠海马中PI3K、Akt、磷酸化（p）-Akt、GSK-3

、p-GSK-3

蛋白表达情况。

结果

与空白组比较，模型组大鼠FINS、HOMA-IR值均显著增高（

0.01）；找到平台原位置的路径显著增长，逃避潜伏期显著延长（

0.01）；海马组织神经细胞形态破坏；大鼠海马活性氧（ROS）、丙二醛（MDA）水平升高和超氧化物歧化酶（SOD）活性降低（

0.05，

0.01）；PI3K、Akt mRNA表达水平显著降低（

0.01），NF-

B、TNF-

和IL-1

mRNA表达水平升高（

0.05，

0.01）；PI3K、p-Akt、p-GSK-3

蛋白表达水平下降（

0.05，

0.01），GSK-3

表达显著增加（

0.01）。与模型组比较，七味白术散中剂量组和联合西药组FINS、HOMA-IR值均显著下降（

0.01）；大鼠找到平台原位置的路径显著缩短，逃避潜伏期缩短（

0.01）；大鼠海马组织结构逐渐恢复，神经细胞形态破坏程度明显改善；大鼠海马组织中ROS、MDA含量降低和SOD水平升高（

0.01）；PI3K、Akt mRNA表达水平显著升高（

0.01），NF-

B、TNF-

和IL-1

mRNA表达水平降低（

0.05，

0.01）；PI3K、p-Akt、p-GSK-3

蛋白表达升高，GSK-3

表达显著降低（

0.01）。

结论

七味白术散可以缓解DE大鼠的胰岛素抵抗，其可能是通过激活PI3K/Akt/GSK-3

信号通路来修复DE大鼠海马神经元损伤，改善DE大鼠学习认知能力。

Abstract

Objective

To observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3

（GSK-3

） signaling pathway.

Method

Forty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg

-1

of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg

-1

）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg

-1

）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-

B（NF-

B）， tumor necrosis factor-

（TNF-

） and interleukin-1

（IL-1

） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3

and p-GSK-3

in hippocampus of rats.

Result

Compared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（

0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（

0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（

0.05，

0.01）， mRNA expression levels of PI3K and Akt were decreased（

0.01）， mRNA expression levels of NF-

B， TNF-

and IL-1

were increased（

0.05，

0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3

were significantly decreased， and the protein expression of GSK-3

was significantly increased（

0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（

0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（

0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（

0.01）， the mRNA expression levels of PI3K and Akt were increased（

0.01）， and the mRNA expression levels of NF-

B， TNF-

and IL-1

were decreased （

0.05，

0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3

were significantly increased（

0.01）， and the expression of GSK-3

was significantly decreased（

0.01）.

Conclusion

QWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3

signaling pathway.

关键词

Keywords

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Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20231163

摘要

Abstract

关键词

Keywords

references