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电针治疗对糖尿病脂肪肝大鼠肝脏Akt/FoxO1信号通路的影响

[Effect of electroacupuncture on liver Akt/FoxO1 signaling pathway in rats with diabetic fatty].

作者信息

Dong Ying, Li Rui, Guo Wei-Xing, Mo Fang-Fang, Song Shan-Shan, Duan Hao-Ru, Zhuang Shu-Ting, Guo Meng-Wei

机构信息

College of Acupuncture-Moxibustion and Tuina, Beijing University of CM, Beijing 102401, China.

College of TCM, Beijing University of CM, Beijing 102401, China.

出版信息

Zhongguo Zhen Jiu. 2023 Jun 12;43(6):679-83. doi: 10.13703/j.0255-2930.20220505-k0006.

DOI:10.13703/j.0255-2930.20220505-k0006
PMID:37313562
Abstract

OBJECTIVE

To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.

METHODS

Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.

RESULTS

Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (<0.01), while the protein expression of hepatic Akt was decreased (<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (<0.01), while the protein expression of hepatic Akt was increased (<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.

CONCLUSION

EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.

摘要

目的

观察电针(EA)对Zucker糖尿病肥胖(ZDF)大鼠肝脏蛋白激酶B(Akt)/叉头框转录因子1(FoxO1)信号通路的影响,探讨EA改善2型糖尿病肝脏胰岛素抵抗的可能机制。

方法

选取12只2月龄雄性ZDF大鼠,给予高脂饮食喂养4周以建立糖尿病模型。造模成功后,将大鼠随机分为模型组和EA组,每组6只。另外,选取6只雄性Zucker瘦素(ZL)大鼠作为空白组。EA组大鼠于双侧“足三里”(ST 36)、“三阴交”(SP 6)、“胃脘下俞”(EX - B 3)和“脾俞”(BL 20)进行电针治疗。将同侧的“足三里”(ST 36)和“胃脘下俞”(EX - B 3)连接电针仪,连续波,频率15 Hz,每次20 min,每天1次,每周6次,共4周。比较每组造模前、干预前及干预后的空腹血糖(FBG);采用放射免疫分析法测定血清胰岛素(INS)和C肽水平,并计算胰岛素抵抗指数(HOMA - IR);采用苏木精 - 伊红(HE)染色法观察肝组织形态;采用蛋白质印迹法检测肝脏中Akt、FoxO1和磷酸烯醇式丙酮酸羧激酶(PEPCK)的蛋白表达。

结果

干预前,与空白组比较,模型组和EA组FBG升高(<0.01);干预后,与模型组比较,EA组FBG降低(<0.01)。与空白组比较,模型组血清INS和C肽水平、HOMA - IR以及肝脏FoxO1和PEPCK蛋白表达升高(<0.01),而肝脏Akt蛋白表达降低(<0.01)。与模型组比较,EA组血清INS和C肽水平、HOMA - IR以及肝脏FoxO1和PEPCK蛋白表达降低(<0.01),而肝脏Akt蛋白表达升高(<0.01)。模型组肝细胞结构紊乱,排列随机,细胞质内有大量脂滴空泡。EA组肝细胞形态趋于正常,脂滴空泡减少。

结论

EA可降低ZDF大鼠的FBG和HOMA - IR,改善肝脏胰岛素抵抗,其机制可能与调节Akt/FoxO1信号通路有关。

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