1.中国科学技术大学附属第一医院(安徽省立医院)感染病院,合肥 230022;2.武汉大学动物实验中心/ ABSL-III 实验室,武汉 430071
R-33
1. Infectious Disease Hospital, the First Affiliated Hospital of University of Science and Technology of China, Hefei 230022, China. 2. Center for Animal Experiment, Wuhan University, Wuhan 430071
目的 探讨HIV 对大脑颞叶皮层神经元中次黄嘌呤核苷酸脱氢酶II(inosine monophosphate dehydrogenase 2,IMPDH2)蛋白表达的影响。 方法 应用MoCA 分数和磁共振成像手段评估HIV 感染者轻度认知障碍情况。利用中国恒河猴SHIV KU-1 神经艾滋病模型,HE 染色观察猴颞叶皮层细胞结构的变化;采用免疫组化方法和Western blot方法检测IMPDH2 在猴颞叶皮层神经元内的表达;以及借助在线数据库预测IMPDH2 相关信号通路的关键信号分子。 结果 HIV 感染者颞叶皮质较健康对照萎缩。与健康对照相比,SHIV KU-1 感染恒河猴颞叶皮层神经元中IMPDH2 蛋白表达显著降低(P<0. 0001)。HNRNPA1 等8 个基因与IMPDH2 有潜在的相互作用。 结论 IMPDH2 在HIV 患者颞叶皮层神经元中的表达下调,其可能参与了HIV 相关神经认知障碍发生。
Objective To investigate the effect of HIV infection on inosine-5’-monophosphate dehydrogenase 2(IMPDH2) expression in the cerebral temporal cortex. Methods Montreal Cognitive Assessment (MoCA) scores and magnetic resonance imaging were used to assess mild cognitive impairment in HIV-infected patients. In addition, the histologic structure of the temporal cortex in a rhesus macaque with chronic simian-human immunodeficiency virus (SHIV) KU-1 infection was examined using hematoxylin and eosin staining. Moreover, IMPDH2 protein expression levels in paired healthy and infected temporal cortex were examined using immunohistochemistry and Western blot. Finally, putative genes associated with IMPDH2 expression were investigated using protein-protein interaction network analysis. Results HIV positive individuals had a thinner temporal cortex compared with healthy controls. In addition, the numbers of neurons in the temporal cortex were decreased and IMPDH2 protein levels were significantly lower in the infected monkey compared with healthy controls. Eight genes interacting with the IMPDH2 gene were identified. Conclusions Downregulation of IMPDH2 protein in the temporal cortex might be involved in the pathogenesis of HIV-related neurocognitive disease.
赵长城,丁华明,鹿伦山,张 千,杨 静,董 颖,薛群山,庄 柯. SHIV KU-1 感染恒河猴颞叶皮层中IMPDH2 的表达[J].中国比较医学杂志,2023,33(7):34~40.
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