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-β1/Smad3 Signaling Pathway on Cognitive Impairment in Obstructive Sleep Apnea Syndrome Rats

作　　者：薛志远 岳宇娇 黄琴 徐源 周雪 向桃 程明 徐平 XUE Zhi-yuan;YUE Yu-jiao;HUANG Qin;XU Yuan;ZHOU Xue;XIANG Tao;CHENG Ming;XU Ping(Sichuan Provincial People’s Hospital Jinniu Hospital,Chengdu 610032,China;Affiliated Hospital of Guizhou Medical University,Guizhou Zunyi,563099,China)

机构地区：[1]成都市金牛区人民医院,成都610032 [2]遵义医科大学附属医院,贵州遵义563099

出　　处：《神经损伤与功能重建》2023年第2期63-67,共5页Neural Injury and Functional Reconstruction

基　　金：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：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(70μg/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。Objective: 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 p Smad3 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 i

关 键 词：阻塞性睡眠呼吸暂停综合症 认知功能障碍 TGF-Β1 SMAD3 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学] R743