| 摘要: |
| 目的 探讨长链非编码RNA（LncRNA）X染色体失活特异转录本（XIST）调节miR-27a-3p信号通路对创伤性脑损伤（TBI）小鼠认知功能和神经炎症的影响。方法 小鼠随机分为TBI组、sh-NC组、sh-LncRNA XIST组、sh-LncRNA XIST+antagomir NC组、sh-LncRNA XIST+miR-27a-3p antagomir组、对照组，每组12只。除对照组外，其它组小鼠均需构建TBI模型。建模24 h后，侧脑室注射生理盐水或药物处理，48 h后，开始检测指标。Morris水迷宫实验检测小鼠逃避潜伏期、穿越平台数；qRT-PCR检测损伤处海马组织中LncRNA XIST、miR-27a-3p表达；HE染色检测损伤处海马组织的病理；免疫荧光染色检测损伤处海马组织中Iba1阳性细胞数；ELISA检测损伤处海马组织中诱导型一氧化氮合酶（iNOS）、精氨酸酶1（Arg-1）、白细胞介素（IL）-1β、IL-6、IL-10 水平；LncRNA XIST与miR-27a-3p关系的验证。结果 与对照组比较，TBI组小鼠损伤处海马组织水肿，且有大量炎性细胞浸润，逃避潜伏期变长，穿越平台数变少，损伤处海马组织中LncRNA XIST表达、Iba1阳性细胞数、iNOS、IL-1β、IL-6水平升高，损伤处海马组织中miR-27a-3p表达、Arg-1、IL-10水平降低（P＜0.05）；与TBI组、sh-NC组比较，sh-LncRNA XIST组小鼠损伤处海马组织水肿及炎性细胞浸润现象有所缓解，逃避潜伏期变短，穿越平台数变多，损伤处海马组织中LncRNA XIST表达、Iba1阳性细胞数、iNOS、IL-1β、IL-6水平降低，损伤处海马组织中miR-27a-3p表达、Arg-1、IL-10水平升高（P＜0.05）；miR-27a-3p antagomir逆转了沉默LncRNA XIST对TBI小鼠认知功能、小胶质细胞极化及神经炎症的影响；LncRNA XIST靶向调控miR-27a-3p。结论 沉默LncRNA XIST可能通过上调miR-27a-3p表达改善TBI小鼠认知功能，促进小胶质细胞由M1型向M2型转化，抑制神经炎症。 |
| 关键词: 长链非编码RNA X染色体失活特异转录本 miR-27a-3p 认知功能 神经炎症 |
| DOI： |
| 分类号: |
| 基金项目:邯郸市科技专项计划项目(编号22422083094ZC) |
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| Effect of LncRNA XIST on cognitive function and neuroinflammation in mice with traumatic brain injury by regulating the miR-27a-3p signaling pathway |
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ZHANG Haiyan, ZHANG Xiaojuan, ZHANG Weiwei
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North China Medical Health Group Fengfeng General Hospital
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| Abstract: |
| Objective To investigate the effects of long non coding RNA (LncRNA) X chromosome inactivation specific transcript (XIST) on cognitive function and neuroinflammation in mice with traumatic brain injury (TBI) by regulating the miR-27a-3p signaling pathway. Methods Mice were randomly separated into TBI group, sh-NC group, sh-lncRNA XIST group, sh-lncRNA XIST+antagomir NC group, sh-lncRNA XIST+miR-27a-3p antagomir group, and control group, with 12 mice in each group. Except for the control group, TBI models were constructed in all other groups. After 24 hours of modeling, physiological saline or drug treatment was injected into the lateral ventricle, and after 48 hours, indicators were detected. Morris water maze experiment was applied to detect the escape latency and number of crossing platforms in mice. QRT-PCR was used to measure the expression of LncRNA XIST and miR-27a-3p in the hippocampal tissue at the site of injury. HE staining was used to detect the pathology of hippocampal tissue at the site of injury. Immunofluorescence staining was used to detect the number of Iba1 positive cells in the hippocampal tissue at the site of injury. ELISA was applied to detect the levels of inducible nitric oxide synthase (iNOS), arginase 1 (Arg-1), interleukin-1 β, IL-6, and IL-10 in the hippocampal tissue at the site of injury. The relationship between LncRNA XIST and miR-27a-3p was validated. Results Compared with the control group, the TBI group showed edema in the damaged hippocampal tissue of mice, with a large amount of inflammatory cell infiltration, the escape latency period became longer and the number of crossing platforms decreased, the expression of LncRNA XIST, the number of Iba1 positive cells, the levels of iNOS, IL-1 β, and IL-6 in the hippocampal tissue at the site of injury increased, the expression of miR-27a-3p, the levels of Arg-1, and IL-10 in the hippocampal tissue at the site of injury reduced (P<0.05). Compared with the TBI group and sh-NC group, the sh-LncRNA XIST group showed some relief in hippocampal tissue edema and inflammatory cell infiltration at the site of injury in mice, the escape latency period became shorter, and the number of crossing platforms increased, the expression of LncRNA XIST, the number of Iba1 positive cells, the levels of iNOS, IL-1 β, and IL-6 in the hippocampal tissue at the site of injury decreased, the expression of miR-27a-3p, the levels of Arg-1, and IL-10 in the hippocampal tissue at the site of injury increased(P<0.05). MiR-27a-3p antagomir reversed the effects of silencing LncRNA XIST on cognitive function, microglial polarization, and neuroinflammation in TBI mice. LncRNA XIST targeted and regulated miR-27a-3p. Conclusion Silencing LncRNA XIST may improve cognitive function in TBI mice by upregulating miR-27a-3p expression, promote the transformation of microglia from M1 to M2, and inhibit neuroinflammation. |
| Key words: long non coding RNA X chromosome inactivation specific transcript miR-27a-3p cognitive function neuroinflammation |