氙气对新生大鼠脑白质损伤脑组织microRNA-210和缺氧诱导因子-1α表达的影响  

Impact of Xenon on expression of microRNA-210 and hypoxia inducible factor-1αin neonatal rats with white matter damage

作　　者：尹向云[1] 赵吉秀 李向红[1] 李亮亮[1] 马丽丽[1] 锡洪敏[1] 姜红[1] Yin Xiangyun;Zhao Jixiu;Li Xianghong;Li Liangliang;Ma Lili;Xi Hongmin;Jiang Hong(Department of Neonatology,the Affiliated Hospital of Qingdao University,Qingdao 266000,China;Jining First People's Hospital,Jining 272000,China)

机构地区：[1]青岛大学附属医院新生儿科,266000 [2]济宁市第一人民医院,272000

出　　处：《中国小儿急救医学》2024年第4期269-275,共7页Chinese Pediatric Emergency Medicine

摘　　要：目的通过检测脑组织内微小RAN-210(microRNA-210,miR-210)及缺氧诱导因子-1α(HIF-1α)表达水平,探讨氙气治疗新生大鼠脑白质损伤的分子基础及神经保护作用机制。方法将3日龄新生SD大鼠120只随机分为3组,分别为假手术组(n=24)、模型组(n=24)和氙气干预组(n=72)。假手术组腹腔内注射等量生理盐水(0.05 mg/kg)后不做任何处理;模型组给予腹腔注射脂多糖(LPS,0.05 mg/kg)3 h后结扎其右侧劲总动脉后置于低氧箱中(8%氧气+92%氮气混合气体)1 h,不进行氙气干预。氙气干预组随机分为A组(n=24)、B组(n=24)和C组(n=24),分别于缺氧缺血处理后0 h、2 h和5 h给予吸入氙气3 h,上述处理后0 h、24 h、48 h、72 h各取6只新生鼠处死取脑,行HE染色、采用UNEL检测细胞凋亡、实时荧光定量RT-PCR法检测miR-210的表达及Western blot检测HIF-1α蛋白含量。结果(1)模型组新生鼠脑室周围脑白质组织层次疏松化,细胞结构排列紊乱,可见核碎裂;氙气干预各亚组大鼠病理变化较模型组明显减轻,细胞凋亡数目明显减少,差异有统计学意义(P<0.05);(2)与假手术组相比,模型组miR-210的表达水平均明显增加;与模型组相比,氙气干预A组脑组织中miR-210的表达在0 h和48 h显著升高,差异均有统计学意义(P<0.05);(3)模型组HIF-1α表达较假手术组显著升高,与模型组相比,氙气干预A组HIF-1α水平明显升高,差异均有统计学意义(P<0.05)。结论氙气可通过上调HIF-1α的表达及其靶基因miR-210,抑制神经元凋亡,减轻缺氧缺血性脑组织损伤,且越早干预效果越好。Objective To reveal the molecular basis and neuroprotective mechanism of Xenon intervention in treating white matter damage by detecting the expression level of microRNA 210(miR-210)and hypoxia inducible factor-1α(HIF-1α)in brain tissues of neonatal rats.Methods Three-day-old SD rats were randomly divided into sham group(n=24),model group(n=24)and Xenon inhalation-group(n=72).Sham group were injected intraperitoneally with normal saline(0.05 mg/kg)only,without any other treatment.Model group were handled with hypoxia-ischemia treatment for 1 hour after intraperitoneal injection with lipopolysaccharide(LPS,0.05 mg/kg)3 hours.The onset of Xenon inhalation started at 0,2 and 5 hours after treatment of LPS injection and hypoxia-ischemia cultivation,and divided in subgroups A(n=24),B(n=24),and C(n=24)respectively.We investigated the neurobehavioral deficits by performing TUNEL and H&E staining and examining the expression of miR-210 and HIF-1αin brain tissues.Results(1)That the brain tissues of neonatal rat which stained by H&E were pale,and psychosis along with apoptosis in model group,while less necrosis or structure distortion were found in Xenon treated groups,the quantity of cell necrosis showed statistically significant decrease in Xenon groups(P<0.05).(2)The expression levels of miR-210 increased significantly at all time points in model group when compared to sham group(P<0.05),while the levels were significantly lower at 0 h and 48 h than those in group A(P<0.05).Compared with group A,the expression levels of miR-210 in group B and group C decreased significantly at 0 h,24 h and 48 h after Xenon inhalation(P<0.05);(3)The expression levels of HIF-1αprotein were statistically differentiated with each other at every time point(P<0.05).The level of HIF-1αprotein in model group were significantly higher than those in sham group at each time point,while significantly lower than those in group A at each time point and those in group B/C at 0 h,24 h and 72 h after Xenon inhalation(P<0.05).Compared with group A a

关 键 词：早产儿 脑白质损伤 氙气 MicroRNA-210 缺氧诱导因子-1Α 

分 类 号：R722.1[医药卫生—儿科]