支链氨基酸转氨酶1基因沉默对缺血脑损伤大鼠的保护作用  

Protective effects of branched-chain amino acid aminotransferase 1 gene silencing on ischemic brain injury in rats

作　　者：曹艳 李恒希 吴抖威 李佳丽 凌腾晗 蒋鸿雁 李坪[1] 郭小兵[1] Cao Yan;Li Hengxi;Wu Douwei;Li Jiali;Ling Tenghan;Jiang Hongyan;Li Ping;Guo Xiaobing(Department of Human Anatomy,Histology and Embryology,Kunming Medical University,Kunming 650500;Department of Pathology,Suining Central Hospital,Suining 629000,China)

机构地区：[1]昆明医科大学人体解剖学与组织胚胎学系,昆明650500 [2]遂宁市中心医院病理科,遂宁629000

出　　处：《神经解剖学杂志》2022年第3期321-326,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(82060241,81960817);云南省教育厅科学研究基金(2017zDX164);昆明医科大学联合专项(202101AY070001-037);昆明医科大学联合重点专项(202101AY070001-002)。

摘　　要：目的:探讨支链氨基酸转氨酶1(BCAT1)基因沉默对大鼠缺血性脑损伤的保护作用。方法:选取40只成年雄性SD大鼠随机分为假手术组(sham)、MCAO模型组(MCAO)、MCAO+空白质粒脑室注射组(NC-shRNA)、MCAO+BCAT1干扰质粒脑室注射组(BCAT1-shRNA),利用大脑中动脉栓塞法(MCAO)制备脑缺血模型,通过神经功能缺损评分判断大鼠神经功能损伤情况;real time RT-PCR检测大鼠脑缺血部位BCAT1 mRNA的表达水平;利用商品化试剂盒测定缺血脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;TUNEL染色检测缺血脑组织细胞凋亡情况。结果:MCAO组大鼠神经功能缺损评分升高(P<0.05),BCAT1 mRNA表达水平升高(P<0.05),脑组织梗死灶增大,SOD活性降低(P<0.05),MDA水平升高(P<0.05),TUNEL染色阳性细胞数量增多(P<0.05)。而BCAT1基因沉默可降低缺血性脑损伤后大鼠神经功能缺损评分(P<0.05),降低BCAT1 mRNA表达水平(P<0.05),缩小脑组织梗死灶范围,上调SOD活性(P<0.05),下调MDA含量(P<0.05),减少细胞凋亡(P<0.05)。结论:大鼠脑缺血可导致BCAT1表达上调,BCAT1基因沉默具有一定神经保护作用。Objective: To investigate the effect of branched-chain amino acid aminotransferase 1(BCAT1) gene silencing on secondary damage and neurological recovery after ischemic brain injury in rats. Methods: Forty adult male Sprague-Dawley rats were randomly divided into sham group(Sham group), MCAO model group(MCAO group), MCAO+blank plasmid intraventricular injection group(NC-shRNA group), MCAO+BCAT1 interference plasmid intraventricular injection group(BCAT1-shRNA group). The cerebral ischemia model was established by middle cerebral artery occlusion(MCAO). The neurological function damage in rats was detected by neurological deficit score. The expression of BCAT1 mRNA in rat cerebral ischemia was detected by real time RT-PCR. The activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in ischemic brain tissue were determined by commercial kits. Apoptosis in ischemic brain tissue was detected by TUNEL staining. Results: In the MCAO group, the neurological deficit score increased(P<0.05), the expression level of BCAT1 mRNA increased(P<0.05), the brain tissue infarction increased, the activity of SOD decreased(P<0.05), the level of MDA increased(P<0.05), and the number of TUNEL positive cells increased(P<0.05). However, BCAT1 gene silencing reduced the neurological deficit score in rats after ischemic brain injury(P<0.05), reduced the expression level of BCAT1 mRNA(P<0.05), narrowed the infarct area of brain tissue, upregulated SOD activity(P<0.05), downregulated MDA content(P<0.05) and decreased apoptosis(P<0.05). Conclusion: Cerebral ischemia in rats leads to upregulation of BCAT1 expression, and BCAT1 gene silencing has some neuroprotective effects.

关 键 词：支链氨基酸转氨酶1 缺血性脑损伤 神经保护 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]