| 薛志远
，岳宇娇
，黄琴
，徐源
，周雪
，向桃
，程明
，徐平.TGF-β1/Smad3信号通路在阻塞性睡眠呼吸暂停综合征大鼠认知障碍中的作用[J].神经损伤功能重建,2023,(2):63-67 |
| TGF-β1/Smad3信号通路在阻塞性睡眠呼吸暂停综合征大鼠认知障碍中的作用 |
| Effect of TGF-β 1/Smad3 Signaling Pathway on Cognitive Impairment in Obstructive SleepApnea Syndrome Rats |
| |
| DOI： |
| 中文关键词: 阻塞性睡眠呼吸暂停综合症 认知功能障碍 TGF-β1 Smad3 |
| 英文关键词: obstructive sleep apnea syndrome cognitive dysfunction TGF-β1 Smad3 |
| 基金项目:国家自然科学基金
（No. 82060218）；
贵州省科技厅贵州
省 科 技 计 划 项 目
（No. 黔 科 合 支 撑
[2019]2796号）；
遵义医学院神经病
学研究生工作站
（No. GZZ2017004）；
成都市卫健委科研
课题（No. 2021304） |
|
| 摘要点击次数: 2024 |
| 全文下载次数: 2379 |
| 中文摘要: |
| 目的：探讨TGF-β1/Smad3信号通路在阻塞性睡眠呼吸暂停综合征（OSAS）所致认知功障碍中的作
用及 TGF-β1 的调控作用。方法：应用慢性间歇性缺氧方式（CIH）建造 OSAS 模型，TGF-β1 抑制剂选择
Disitertid（别名P144）。成年雄性SD大鼠42只随机分为7组：正常对照组（N组）、CIH 1W组、CIH 2W组、
CIH 3W组、CIH 4W组、CIH 4W+ P144组、CIH 4W+DMSO组，每组6只；分别给予不同的缺氧时间，其中
CIH 4W+ P144组和CIH 4W+DMSO组于造模前分别腹腔内注射P144（70 µg/kg）和二甲亚砜（1 ml/kg），隔
日1次。造模后，采用水迷宫实验检测大鼠学习及记忆能力，尼氏染色法观察各组大鼠海马CA1及CA3区
的病理学改变，免疫印迹法对各组大鼠海马组织中TGF-β1、tSmad3、pSmad3蛋白定量检测。结果：OSAS
模型大鼠出现白天嗜睡、烦躁等表现，缺氧期间相比复氧相间平均血氧饱和度下降＞4%（P＜0.05），造模成
功。水迷宫实验中，与N组相比，CIH 2W、3W、4W时间点组大鼠逃避潜伏期延长，穿越平台次数减少（均
P＜0.05）；与CIH 4W+DMSO组相比，CIH 4W+P144组大鼠逃避潜伏期缩短，穿越平台次数增加（均P＜
0.05）。尼氏染色光镜观察结果显示，OSAS模型大鼠部分神经细胞结构破坏、尼氏小体数量减少溶解、胞
浆着色浅、最终尼氏小体消失；CIH 4W+P144组尼氏小体数量多，且结构较完整，细胞受损程度相对轻。
与N组比较，TGF-β1、pSmad3在CIH 1W、2W、3W、4W时间点的蛋白表达量递增（均P＜0.05）；与CIH 4W+
DMSO组比较，CIH 4W+P144组TGF-β1、pSmad3蛋白表达量表达下降（均P＜0.05）。结论：OSAS大鼠存
在认知功能障碍，TGF-β1/Smad3信号通路被激活，特异性抑制TGF-β1后OSAS认知障碍大鼠的空间学习
能力及记忆能力一定程度上得到改善。 |
| 英文摘要: |
| To investigate the effect of the TGF-β1/Smad3 signaling pathway on cognitive dysfunction from obstructive sleep apnea syndrome (OSAS) and the regulation of TGF-β1. Methods: Chronic intermittent hypoxia (CIH) was used to construct the OSAS model. Disitertid (P144) was selected for TGF-β1 inhibition. Forty-two adult male SD rats were randomly divided into the following 7 groups with 6 rats in each: normal control (N) group, CIH 1 week (1W) group, CIH 2W group, CIH 3W group, CIH 4W group, CIH 4W+
P144 group, and CIH 4W+DMSO group. Rats in each group were subjected to hypoxia for the corresponding
duration of time. CIH 4W+P144 group rats and CIH 4W+DMSO group rats were intraperitoneally injected with
P144 (70 µg/kg) and DMSO (1 mL/kg) respectively, once every other day, before modeling. After model establishment, the Morris water maze (MWM) was used to detect the learning and memory ability of the rats; Nissl
staining was used to observe the hippocampal CA1 and CA3 neurons for pathological changes; and Western
blotting was used to quantitatively detect TGF-β1, tSmad3, and pSmad3 proteins in the hippocampus of rats in
each group. Results: OSAS model rats displayed daytime sleepiness and irritability and compared with in reoxygenation time, the mean oxygen saturation decreased by > 4% in hypoxia time (P<0.05), which indicating successful model establishment. For rats in the CIH 2W, 3W, and 4W groups compared to those in the N group, escape latency was prolonged, and the number of platform crossings was decreased (all P<0.05) in MWM. Compared to rats in the CIH 4W+DMSO group, rats in the 4W+P144 showed a decreased escape latency and increased platform crossings (all P<0.05). Nissl staining in OSAS model rats showed nerve cell structural damage, reduced numbers of Nissl bodies, lightly stained cytoplasm, and the eventual disappearance of Nissl bodies. The CIH 4W+P144 group showed a large number of Nissl bodies and relatively complete structure, with
the degree of cell damage being relatively light. Compared to that in N group rats, the expression of TGF-β1
and pSmad3 in the CIH 1W, 2W, 3W, and 4W rats was increased (all P<0.05). The expression of TGF-β1 and
pSmad3 protein decreased in the 4W+P144 group compared with the 4W+DMSO group (all P<0.05). Conclusion: The TGF-β1/Smad3
signaling pathway is activated in cognitive dysfunction in OSAS rats. The spatial learning and memory ability of cognitively impaired
OSAS rats is improved to some extent after specific inhibition of TGF-β1. |
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