| 邹敏,孙应中,魏艳妮,等.七氟烷对 β淀粉样蛋白 1-40诱导的大鼠认知功能障碍影响及机制[J].安徽医药,2024,28(3):456-461. |
| 七氟烷对 β淀粉样蛋白 1-40诱导的大鼠认知功能障碍影响及机制 |
| Effect and mechanism of sevoflurane on cognitive dysfunction induced by β Amyloid protein 1-40 in rats |
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| DOI：10.3969/j.issn.1009-6469.2024.03.007 |
| 中文关键词: 七氟醚 β淀粉样蛋白 1-40 海马 认知功能障碍 阿尔茨海默病 |
| 英文关键词: Sevoflurane β Amyloid protein 1-40 Hippocampus Cognitive dysfunction Alzheimer's disease |
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| 中文摘要: |
| 目的探讨七氟烷吸入对 β淀粉样蛋白( Aβ)1-40诱发的大鼠认知功能障碍影响及其可能的机制。方法于 2021年 8月至 2022年 8月，将 32只成年雄性 Sprague-Dawley大鼠以随机数字表法分为生理盐水( NS)+氧气组、 NS+七氟烷组、 Aβ+氧气组和 Aβ+七氟烷组，每组 8只，分别给予双侧海马内注射 NS或 Aβ1-40。吸入 30%氧气或 2.5%七氟烷过程中监测生命体征，采用 Morris水迷宫实验检测大鼠认知功能；酶联免疫吸附测定检测海马 Aβ1-40水平；免疫组织化学法检测胶质纤维酸性蛋白(GFAP)和离子钙接头蛋白分子 1(IBA1)的表达；实时荧光定量逆转录聚合酶链反应检测白细胞介素 -1β(IL-1β)、核因子 -κB(NF-κB)、诱导型一氧化氮合酶( iNOS)的 mRNA表达；蛋白质印迹法检测 B淋巴细胞瘤 -xL(Bcl-xL)、胱天蛋白酶 -9(caspase-9)、脑源性神经营养因子( BDNF)和晚期糖基化终末产物受体( RAGE)的蛋白表达。结果维持吸入 2.5%七氟烷在 4个不同时间点( 1、2、3和 4h)对大鼠生命体征无影响。与 NS+氧气组比较， Aβ+氧气组大鼠原始平台探索时间减少，逃逸潜伏期增加；与 Aβ+氧气组相比， Aβ+七氟烷组大鼠原始平台探索时间减少，逃逸潜伏期增加( P<0.05)。 Aβ+七氟烷组大鼠海马区 Aβ1-40水平［( 42.18±5.72)ng/L］，GFAP和 IBA1阳性细胞数［( 24.33±1.21)个和( 37.82±3.23)个］，caspase-9和 RAGE蛋白表达( 0.74±0.11和 0.81±0.07)IL-1β、NF-κB和 iNOS mRNA表达( 28.98±12.32、25.91±12.31和 43.92±17.21)均高于 NS+七氟烷组［(18.13±2.89)ng/ L、(10.51±06)个、(17.17±1.77)个、 0.23±0.02、0.29±0.03、1.35±0.04、1.37±0.05、1.42±0.06］和 Aβ+氧气组［( 32.61±4.82)ng/L、.9(15.76±1.25)个、(24.76±2.31)个、 0.45±0.08、0.68±0.08、10.23±6.56、6.51±2.34、13.23±4.81］； Bcl-xL和 BDNF蛋白表达(0.13±0.04和 0.18±0.04)低于 NS+七氟烷组( 1.07±0.31和 0.58±0.07)和 Aβ+氧气组( 0.46±0.11和 0.33±0.04)(P<0.05)。而 NS+氧气组和 NS+七氟烷组之间各指标差异无统计学意义( P>0.05)。结论七氟烷通过启动大鼠海马的神经毒性、神经炎症和神经元凋亡，加剧了 Aβ1-40诱发的大鼠认知功能障碍。 |
| 英文摘要: |
| Objective To investigate the effects of sevoflurane inhalation on cognitive dysfunction induced by β Amyloid protein 1-40 in rats and its possible mechanism.Methods From August 2021 to August 2022, 32 adult male Sprague-Dawley rats were divided intonormal saline (NS)+oxygen group, NS+sevoflurane group, Aβ+oxygen group, and Aβ+sevoflurane group by random number table meth.od, with 8 rats in each group, and were given bilateral intra-hippocampal injection of NS or Aβ1-40, respectively. Vital signs were moni. tored during inhalation of 30% oxygen or 2.5% sevoflurane, and cognitive function was detected by Morris water maze test. The levelsof Aβ1-40 in hippocampus were detected by enzyme-linked immunosorbent assay. The expressions of glial fibrillary acidic protein(GFAP) and IBA1 were detected by immunohistochemistry. The mRNA expression of interleukin-1β (IL-1β), nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) was detected by real-time fluorescence quantitative polymerase chain reaction. Protein expression of B lymphoblastoma xL (Bcl-xL), cysteine-containing aspartate protein hydrolase-9 (caspase-9), brain-derived neurotrophic factor (BDNF), and advanced glycosylated end-product receptor (RAGE) were detected by Western blotting. Results Inhalation of 2.5% sevoflurane at 4 different time points (1, 2, 3 and 4h) had no effect on the vital signs of rats. Compared with NS+oxygen group, theexploration time of the original platform was reduced and the escape latency was increased in Aβ +oxygen group. Compared withAβ+oxygen group, the original platform exploration time of rats in Aβ+sevoflurane group decreased and the escape latency increased (P< 0.05). The levels of Aβ1-40 [(42.18±5.72) ng/L], the number of GFAP and IBA1 positive cells (24.33±1.21 and 37.82±3.23), the ex. pression of caspase-9 and RAGE protein (0.74±0.11 and 0.81±0.07), the mRNA expressions of IL-1β, NF-κB and iNOS(28.98±12.32,25.91±12.31, and 43.92±17.21) in Aβ+sevoflurane group were higher than those in NS+sevoflurane group [(18.13±2.89) ng/L, 10.51±0.96, 17.17±1.77, 0.23±0.02, 0.29±0.03, 1.35±0.04, 1.37±0.05, 1.42±0.06] and Aβ +oxygen group [(32.61±4.82) ng/L, 15.76±1.25,24.76±2.31, 0.45±0.08, 0.68±0.08, 10.23±6.56, 6.51±2.34, 13.23±4.81], the protein expressions of Bcl-xL and BDNF (0.13±0.04 and0.18±0.04) were lower than those of NS+sevoflurane group (1.07±0.31 and 0.58±0.07) and Aβ +oxygen group(0.46±0.11 and 0.33±0.04) (P<0.05). There was no significant difference between NS+oxygen group and NS+sevoflurane group (P>0.05). Conclusion Sevoflurane can aggravate the cognitive dysfunction induced by Aβ1-40 by activating neurotoxicity, neuroinflammation and neuronal apoptosis in rat hippocampus. |
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