Sleeve gastrectomy attenuated diabetes-related cognitive decline in diabetic rats.

Sleeve gastrectomy attenuated diabetes-related cognitive decline in diabetic rats.
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袖状胃切除术减轻了糖尿病大鼠与糖尿病相关的认知能力下降

DOI:
10.3389/fendo.2022.1015819
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发表时间:
2022
影响因子:
5.2
通讯作者:
Zhang, Guangyong
Zhang, Guangyong
中科院分区:
医学2区
文献类型:
--
作者:
Ding, Huanxin;Liu, Chuxuan;Zhang, Shuo;Li, Bingjun;Xu, Qian;Shi, Bowen;Li, Songhan;Dong, Shuohui;Ma, Xiaomin;Zhang, Yun;Zhong, Mingwei;Zhang, Guangyong

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探讨袖胃切除术(SG)对糖尿病(DM)大鼠糖尿病相关性认知能力下降(DCD)的影响。40只Wistar大鼠随机分为对照组(CON)、糖尿病(DM)组(n=10)、假手术(sham)组(n=10)和SG组(n=10)。采用高脂饲料(HFD)联合腹腔注射链脲佐菌素(STZ)建立DM模型。采用Morris水迷宫和y型迷宫进行行为评价。采用PET-CT、TUNEL、组织学分析、透射电镜(TEM)、免疫组化(IHC)、Western blot等方法评价SG对DM大鼠DCD的缓解作用及可能机制。与假药组比较,SG能显著改善血糖、体重等代谢指标。与SHAM组相比,可明显减轻胰岛素抵抗。此外,SG还能改善DM大鼠的认知功能,与SHAM组相比,DM大鼠的逃避潜伏期显著降低(P<0.05),目标象限和平台穿越时间显著增加(P<0.05)。与SHAM组比较,SG组自发性交变明显升高(P<0.05)。此外,SG还能促进海马神经元的排列和生物合成。此外,SG触发了海马神经元凋亡的抑制,Western blot分析显示SG诱导Bcl-2/Bax和Caspase3/cleaved Caspase3比值显著升高。透射电镜显示,与SHAM组相比,SG能显著改善海马神经元的微观结构。Western blot和免疫组化证实SG组tau蛋白Ser404和Ser396位点的磷酸化显著降低。此外,与SHAM组相比,SG通过提高PI3K、Akt和GSK3β的磷酸化来激活PI3K信号通路。SG能减弱DM大鼠的DCD,可能与激活PI3K信号通路有关。
To investigate the effects of sleeve gastrectomy (SG) on diabetes-related cognitive decline (DCD) in rats with diabetic mellitus (DM). Forty Wistar rats were randomly divided into control (CON) group (n=10), diabetes mellitus (DM) group (n=10), sham operation (SHAM) group (n=10) and SG group (n=10). DM model was established by high-fat diet (HFD) combined with intraperitoneal injection of streptozocin (STZ). Behavioral evaluation was given using Morris water maze test and Y-maze. In addition, PET-CT, TUNEL assay, histological analysis, transmission electron microscopy (TEM), immunohistochemistry (IHC) and Western blot analysis were used to evaluate the alleviating effects and potential mechanisms of SG on DCD in DM rats. Compared with the sham group, SG induced significant improvement in the metabolic indices such as blood glucose and body weight. Besides, it could attenuate the insulin resistance compared with SHAM group. In addition, SG could improve the cognitive function of DM rats, which were featured by significant decrease in the escape latency (P<0.05), and significant increase in the time in target quadrant and platform crossings (P<0.05) compared with the SHAM group. SG induced significant elevation in the spontaneous alternation compared with SHAM group (P<0.05). Moreover, SG could improve the arrangement and biosynthesis of hippocampus neuron. Moreover, SG triggered the inhibition of apoptosis of hippocampus neurons, and Western blot analysis showed SG induced significant increase in the ratios of Bcl-2/Bax and Caspase3/cleaved Caspase 3. TEM demonstrated SG could significantly improve the microstructure of hippocampus neurons compared with the SHAM group. Western blot and IHC confirmed the significant decrease in the phosphorylation of tau at Ser404 and Ser396 sites in the SG group. Furthermore, SG activated the PI3K signaling pathway by elevating the phosphorylation of PI3K and Akt and GSK3β compared with the SHAM group. SG attenuated the DCD in DM rats, which may be related to the activation of PI3K signaling pathway.
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