[Mechanism of electroacupuncture regulating nuclear factor-κB pathway to improve the dedifferentiation of pancreatic β-cells in rats with T2DM].

Publisher: Guoji Shudian Country of Publication: China NLM ID: 8600658 Publication Model: Print Cited Medium: Print ISSN: 0255-2930 (Print) Linking ISSN: 02552930 NLM ISO Abbreviation: Zhongguo Zhen Jiu Subsets: MEDLINE

Publication: Pei-Ching : Guoji Shudian
Original Publication: Beijing : Zhonghua quan guo Zhong yi zhen jiu xue hui : Zhong yi yan jiu yuan zhen jiu yan jiu suo, 1981-

Electroacupuncture* ; Diabetes Mellitus, Type 2*/therapy ; Diabetes Mellitus, Type 2*/metabolism ; Insulin-Secreting Cells*/metabolism ; NF-kappa B*/metabolism ; Rats, Wistar* ; Interleukin-1beta*/metabolism; Animals ; Male ; Rats ; Humans ; Tumor Necrosis Factor-alpha/metabolism ; Signal Transduction ; Cell Dedifferentiation ; Blood Glucose/metabolism ; Acupuncture Points ; Insulin/metabolism

Objective: To observe the effects of electroacupuncture (EA) on the expression of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the pancreatic nuclear factor-κB (NF-κB) pathway in type 2 diabetes mellitus (T2DM) rats, and to explore the possible mechanism by which EA improving the dedifferentiation of pancreatic β-cells in the treatment of T2DM.
Methods: Among 18 SPF-grade male Wistar rats, 6 rats were randomly selected as the control group, and the remaining 12 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of 2% streptozotocin solution (35 mg/kg) to establish T2DM model. After successful modeling, the 12 rats were randomly divided into a model group and an EA group, with 6 rats in each group. The EA group received EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20), with continuous wave, frequency of 15 Hz, current intensity of 2 mA, for 20 min each time, once a day, 6 times a week, for a total of 6 weeks. Fasting blood glucose (FBG) levels were measured before modeling and before and after intervention. After intervention, ELISA was used to detect the serum fasting insulin (FINS), IL-1β and TNF-α levels, and the β-cell function index (HOMA-β) and insulin resistance index (HOMA-IR) were calculated; HE staining was used to observe the morphology of the pancreatic islets; Western blot was used to detect the protein expression of pancreatic forkhead box protein O1 (FoxO1), pancreatic and duodenal homeobox 1 (PDX-1), neurogenin 3 (NGN3), and NF-κB p65.
Results: After intervention, the FBG in the model group was higher than that in the control group ( P <0.01), and the FBG in the EA group was lower than that in the model group ( P <0.01). Compared with the control group, the model group had increased levels of serum FINS, IL-1β, TNF-α, and HOMA-IR ( P <0.01), and decreased HOMA-β ( P <0.01), reduced protein expression of pancreatic FoxO1 and PDX-1 ( P <0.01), and increased protein expression of pancreatic NGN3 and NF-κB p65 ( P <0.01, P <0.05). Compared with the model group, the EA group had lower serum FINS, IL-1β, TNF-α levels, and HOMA-IR ( P <0.01), higher HOMA-β ( P <0.05), increased protein expression of pancreatic FoxO1 and PDX-1 ( P <0.01, P <0.05), and decreased protein expression of pancreatic NGN3 and NF-κB p65 ( P <0.01, P <0.05). The control group's pancreatic islets showed no obvious abnormalities; the model group's pancreatic islets were irregular in shape and had unclear boundaries with the surrounding area, with immune cell infiltration, reduced β-cell nuclei, disordered arrangement of islet cells, and increased intercellular spaces; the EA group showed improvements in islet morphology, immune cell infiltration, β-cell nuclei count, and the arrangement and spacing of islet cells approaching normal.
Conclusion: EA could lower the blood glucose levels in T2DM rats, alleviate chronic inflammatory responses in the islets, and improve the dedifferentiation of pancreatic β-cells, which may be related to the inhibition of pancreatic NF-κB pathway expression.

Keywords: chronic inflammatory response in islets; dedifferentiation of pancreatic β-cells; electroacupuncture; nuclear factor-κB pathway; type 2 diabetes mellitus (T2DM)
Local Abstract: [Publisher, Chinese] 目的： 观察电针对2型糖尿病（T2DM）大鼠血清白介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）及胰腺核因子-κB（NF-κB）通路表达的影响，探讨电针改善胰岛β细胞去分化治疗T2DM的可能机制。 方法： 从18只SPF级雄性Wistar大鼠中随机挑选6只作空白组，余下12只经高糖高脂饲料喂养结合腹腔注射2%链脲佐菌素溶液（35 mg/kg）制备T2DM模型，造模成功后随机分为模型组和电针组，每组6只。电针组以电针干预双侧“足三里”“三阴交”“胃脘下俞”“脾俞”，连续波，频率15 Hz，电流强度2 mA，每次20 min，每日1次，每周6次，持续干预6周。检测造模前及干预前后大鼠空腹血糖（FBG）。干预后，采用ELISA法检测大鼠血清空腹胰岛素（FINS）、IL-1β、TNF-α含量，并计算胰岛β细胞功能指数（HOMA-β）、胰岛素抵抗指数（HOMA-IR）；HE染色法观察大鼠胰岛形态；Western blot法检测大鼠胰腺叉头框架蛋白O1（FoxO1）、胰腺十二指肠同源框1（PDX-1）、神经元素3（NGN3）、NF-κB p65蛋白表达。 结果： 干预后，模型组FBG高于空白组（ P <0.01），电针组FBG低于模型组（ P <0.01）。与空白组比较，模型组血清FINS、IL-1β、TNF-α含量及HOMA-IR升高（ P <0.01），HOMA-β降低（ P <0.01）；胰腺FoxO1、PDX-1蛋白表达减少（ P <0.01），NGN3、NF-κB p65蛋白表达增多（ P <0.01， P <0.05）。与模型组比较，电针组血清FINS、IL-1β、TNF-α含量及HOMA-IR降低（ P <0.01），HOMA-β升高（ P <0.05）；胰腺FoxO1、PDX-1蛋白表达增多（ P <0.01， P <0.05），NGN3、NF-κB p65蛋白表达减少（ P <0.01， P <0.05）。空白组胰岛无明显异常；模型组胰岛形态不规则且与周围边界不清，胰岛存在免疫细胞浸润，β细胞核减少，胰岛细胞排列杂乱、细胞间隙增大；电针组胰岛形态、免疫细胞浸润情况、β细胞核数量较模型组改善，胰岛细胞排列及细胞间隙趋近正常。 结论： 电针可以降低T2DM大鼠血糖，减轻胰岛慢性炎性反应，改善胰岛β细胞去分化，其机制可能与抑制胰腺NF-κB通路表达有关。.

0 (NF-kappa B)
0 (Interleukin-1beta)
0 (Tumor Necrosis Factor-alpha)
0 (Blood Glucose)
0 (Insulin)

Date Created: 20240613 Date Completed: 20240613 Latest Revision: 20240626

20240626

10.13703/j.0255-2930.20230821-k0002

38867629