摘要
目的探究槲皮素(Que)激活过氧化物酶体增殖物激活受体γ共激活因子1(PGC-1α)/核呼吸因子-1(NRF-1)/线粒体转录因子A(TFAM)信号通路对缺氧缺血性脑损伤(HIBD)新生大鼠认知障碍的影响。方法选用新生7日龄SD大鼠144只诱导建立HIBD模型,随机分为假手术(Sham)组,模型(HIBD)组,低、高剂量Que(L-Que、H-Que)组,阳性对照(尼莫地平,Nimo)组及PGC-1α抑制剂+H-Que组,每组24只。采用Morris水迷宫实验评估认知功能;采用烘干法测定脑组织含水量;采用TTC染色测定脑组织梗死体积;采用Tunel染色观察脑组织神经元凋亡情况;采用Western Blot检测大鼠脑组织PGC-1α/NRF-1/TFAM通路中蛋白的相对表达水平。结果与Sham组比较,HIBD组逃避潜伏期、mNSS评分、脑组织含水量、梗死体积、神经元凋亡率分别延长或升高至(48.67±5.14)s、(7.85±1.25)分、(89.57±3.62)%、(27.58±3.53)%、(25.69±3.98)%,穿越原平台次数降低至(1.50±0.38)次(P<0.05)。与HIBD组比较,L-Que组、H-Que组、Nimo组逃避潜伏期分别缩短至(35.71±4.63)s、(26.28±4.31)s、(24.95±4.29)s;mNSS评分分别降低至(5.80±1.02)分、(4.12±0.85)分、(4.25±0.92)分;脑组织含水量分别下降至(82.29±3.35)%、(75.38±3.15)%、(74.59±3.21)%;梗死体积分别下降至(16.39±3.25)%、(9.15±2.42)%、(7.68±2.51)%;神经元凋亡率分别下降至(19.06±2.69)%、(12.38±2.14)%、(11.98±2.09)%;穿越原平台次数分别增加至(3.00±0.35)次、(4.50±0.41)次、(4.50±0.39)次(P<0.05)。与Sham组比较,HIBD组脑组织中PGC-1α、NRF-1、TFAM蛋白表达分别下降至0.29±0.11、0.27±0.12、0.25±0.09(P<0.05)。与HIBD组比较,H-Que组脑组织中PGC-1α、NRF-1、TFAM蛋白表达分别增加至(0.52±0.13)、(0.49±0.10)、(0.41±0.09)(P<0.05)。与H-Que组比较,PGC-1α抑制剂的加入逆转了上述指标的变化趋势(P<0.05)。结论Que能够缓解HIBD新生大鼠认知障碍,其机制涉及PGC-1α/NRF-1/TFAM信号通路的激活。
Objective To explore the impact of quercetin(Que)on cognitive impairment in neonatal rats with hypoxic-ischemic brain damage(HIBD)by activating of PGC-1α/NRF-1/TFAM signaling pathway.Methods 144 neonatal 7-day-old SD rats were selected to establish HIBD models and randomly assigned to sham operation(Sham)group,model(HIBD)group,low and high dose Que(L-Que,H-Que)groups,positive control(Nimodipine,Nimo)group,and PGC-1αinhibitor+H-Que group,with 24 rats in each group.The Morris water maze test was used to evaluate cognitive function;the drying method was used to determine the water content of brain tissue;the infarct volume was measured using TTC staining;neuronal apoptosis was observed using TUNEL staining;Western Blot was used to detect the expression of protein related to the PGC-1α/NRF-1/TFAM signaling pathway in brain tissue.Results Compared with the Sham group,the HIBD group showed an increase in escape latency,mNSS score,brain tissue water content,infarct volume,and neuronal apoptosis rate to(48.67±5.14)s,(7.85±1.25)points,(89.57±3.62)%,(27.58±3.53)%,and(25.69±3.98)%,respectively,while crossings through the original platform decreased to(1.50±0.38)times(P<0.05).Compared with the HIBD group,the escape latency of the L-Que group,H-Que group,and Nimo group decreased to(35.71±4.63)s,(26.28±4.31)s,and(24.95±4.29)s,respectively;The mNSS scores decreased to(5.80±1.02)points,(4.12±0.85)points,and(4.25±0.92)points,respectively;the brain tissue water content decreased to(82.29±3.35)%,(75.38±3.15)%,and(74.59±3.21)%,respectively;The infarct volume decreased to(16.39±3.25)%,(9.15±2.42)%,and(7.68±2.51)%,respectively;The apoptosis rates of neurons decreased to(19.06±2.69)%,(12.38±2.14)%,and(11.98±2.09)%,respectively;The number of crossings through the original platform increased to(3.00±0.35)times,(4.50±0.41)times,and(4.50±0.39)times respectively(P<0.05).Compared with the Sham group,the expression of PGC-1α,NRF-1,and TFAM proteins in the brain tissue of the HIBD group decreased to 0.29±0.11,0.27±0.12,and 0.25±0.09,respectively(P<0.05).Compared with the HIBD group,the expression of PGC-1α,NRF-1,and TFAM proteins in the brain tissue of the H-Que group increased to 0.52±0.13,0.49±0.10,and 0.41±0.09,respectively(P<0.05).Compared with the H-Que group,the addition of PGC-1αinhibitor reversed the trend of changes in the above indicators(P<0.05).Conclusion Que can improve cognitive impairment in neonatal rats with HIBD,and the mechanism involves the activation of PGC-1α/NRF-1/TFAM signaling pathway.
作者
崔艳艳
董嗣庆
王慧
CUI Yanyan;DONG Siqing;WANG Hui(Departments of Neurology,Beidahuang Group General Hospital,Harbin,Heilongjiang 150088,China;Department of Emergency,Beidahuang Group General Hospital,Harbin,Heilongjiang 150088,China)
出处
《转化医学杂志》
2025年第6期129-134,共6页
Translational Medicine Journal
作者简介
通信作者:崔艳艳,硕士研究生,副主任医师。主要从事急慢性脑血管病诊疗方向研究,E-mail:yikedaxuecui@sina.com。
