高脂膳食对小鼠脊髓损伤预后的影响及其机制的初步研究  

A preliminary study on the effect of high-fat diet on the prognosis of post-spinal cord injury mice and its mechanism

作　　者：陈淳 尤涛 Chen Chun;You Tao(Dept of Orthopaedics,The First Affiliated Hospital of University of Science and Technology of China,Hefei 230001;School of Clinical Medicine,School of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001)

机构地区：[1]中国科学技术大学附属第一医院骨科,合肥230001 [2]中国科学技术大学生命科学与医学部临床医学院,合肥230001

出　　处：《安徽医科大学学报》2025年第3期422-429,共8页Acta Universitatis Medicinalis Anhui

基　　金：安徽省高校自然科学研究重大项目(编号:2023AH040394);合肥国家科学中心先导医学与前沿技术项目(重点)(编号:2023IHM01073);安徽省自然科学基金面上项目基金(编号:2008085MH246)。

摘　　要：目的阐明高脂膳食(HFD)与脊髓损伤(SCI)的病理进程以及预后间的内在联系,并初步探讨其可能机制。方法分别建立常规膳食(RD)和HFD小鼠脊髓T9~T12节段打击损伤的模型。苏木精-伊红(HE)染色、马松(Masson)染色和尼氏(Nissl)染色观察SCI局部的组织学变化。BBB评分、足迹试验评估比较RD和HFD小鼠SCI后后肢功能的恢复情况。体外细胞实验筛选HFD中加重神经元损伤的关键成分脂肪酸,体内检测棕榈酸的抑制剂2-溴棕榈酸(2-BP)治疗SCI的HFD小鼠的效应。结果与RD小鼠相比,HFD小鼠SCI后损伤区域显著增大,神经元损伤增多,小鼠后肢功能恢复较差。实验也证明神经元损伤加重的关键脂肪酸是棕榈酸,并进一步验证抑制棕榈酸的棕榈酰化修饰有助于HFD小鼠SCI后神经元的存活,促进组织修复和后肢功能的恢复。结论HFD通过棕榈酸加重了小鼠SCI后的病理性损伤,影响其预后,而棕榈酸介导的棕榈酰化修饰可能是这一效应的主要机制。Objective To clarify the intrinsic link between a high-fat diet(HFD)and the pathological progression and prognosis of spinal cord injury(SCI)while preliminarily exploring the potential underlying mechanisms.Methods SCI models were established in mice that were fed either a regular diet(RD)or HFD,with injury inflicted specifically on the T 9-T 12 segments.Hematoxylin-Eosin(HE)staining,Masson staining,and Nissl staining were used to observe the local histological changes in SCI tissues.The basso,beattie,and bresnahan(BBB)score and footprint analysis were used to evaluate and compare hindlimb functional recovery after SCI in both RD and HFD mice.In vitro experiments were conducted to identify key fatty acids in the HFD that exacerbate neuronal damage,while in vivo experiments assessed the effects of 2-bromopalmitate(2-BP),a palmitic acid inhibitor,on HFD-fed mice with SCI.Results Compared to RD-fed mice,HFD-fed mice exhibited significantly larger lesion areas,more severe neuronal damage,and poorer hindlimb functional recovery after SCI.Palmitic acid was identified as the key fatty acid aggravating neuronal damage.Further more,inhibition of palmitoylation,mediated by palmitic acid,enhanced neuronal survival,promoted tissue repair,and improved hindlimb functional recovery in HFD-fed mice post-SCI.Conclusion HFD exacerbates pathological damage following SCI in mice through palmitic acid,impairing recovery.Palmitic acid-mediated palmitoylation is likely the main mechanism underlying this effect.

关 键 词：高脂饮食 脂肪酸 棕榈酸脂 棕榈酰化修饰 脊髓损伤 预后 

分 类 号：R651.2[医药卫生—外科学]