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| 1 | 基于mTOR通路介导的自噬探讨补阳还五汤对脊髓损伤的保护机制显示文摘目的基于mTOR通路介导的自噬探讨补阳还五汤对脊髓损伤(SCI)后自噬相关蛋白的影响,从而揭示补阳还五汤对SCI的保护机制。方法64只SPF级SD雄性大鼠,随机分为假手术组、模型组、雷帕霉素组、补阳还五汤组。除假手术组外,其余三组均采用Allen’s打击方法制备SCI模型。假手术组、模型组予生理盐水灌胃,补阳还五汤组予补阳还五汤水煎液灌胃(12.73g·kg^(-1)·d^(-1)),在造模前各组分别予相应处理持续3d,雷帕霉素组在造模后0.5h内给予腹腔注射给药(3mg·kg^(-1)·d^(-1));造模3 h、6 h后采用改良Tarlov评分、HE染色、免疫组化实验、免疫印迹实验方法,观察补阳还五汤对下肢运动功能、脊髓前角区神经元的形态结构及mTOR自噬信号通路的影响。结果(1)与假手术组比,造模后3 h、6 h时模型组改良Tarlov评分均显著降低,神经元细胞肿胀、胞核固缩严重,细胞结构完整性丧失,Beclin1、LC3阳性细胞,LC3-II/LC3-I、Beclin1蛋白表达均减少(P<0.05),mTOR阳性细胞及蛋白均表达增加(P<0.05);(2)与模型组比,造模后3 h、6 h时雷帕霉素组、补阳还五汤组改良Tarlov评分均显著降低(P<0.05),神经元细胞肿胀略有减轻,偶尔可见正常的神经元细胞,两组组Beclin1、LC3阳性细胞及LC3-II/LC3-I、Beclin1蛋白表达均升高(P<0.05),mTOR阳性细胞及蛋白表达均减少(P<0.05);(3)与雷帕霉素组比,造模后3 h、6 h时补阳还五汤组改良Tarlov评分差异均无统计学意义(P>0.05),细胞肿胀略减轻、正常神经元稍微增多,造模后3 h时Beclin1阳性细胞,6 h时LC3阳性细胞表达均升高(P<0.05),造模后3h、6 h时LC3-II/LC3-I、Beclin1、mTOR蛋白表达增加(P>0.05)。结论补阳还五汤可以有效地影响细胞自噬水平,改善大鼠下肢运动功能,有效地调控mTOR信号通路,其保护作用可能是通过抑制mTOR信号通路激活细胞自噬而实现的,这可能是其治疗SCI的作用机制之一。 | 卜献忠 张冠鹏 郭晓辉 李寒曦 卜保献 钟远鸣 | 2022 | 时珍国医国药2022，33，4： | 4 |
| 2 | 脊髓损伤中自噬的研究进展显示文摘脊髓损伤(spinal cord injury,SCI)是常见的中枢神经系统疾病之一,在直接或间接损伤的作用下,脊髓功能障碍导致了损伤部位以下的感觉、运动及其他功能丧失。美国国家SCI统计中心统计,美国约有28.8万人患有SCI,每年新增SCI病例17000例,其对患者身心及社会经济造成了巨大损害[1]。根据其病理生理机制,SCI可分为两个阶段:原发性和继发性损伤[2]。原发性损伤包括直接的机械损伤及其造成的轴突、细胞膜及血管损伤。 | 刘方煜 范一鸣 张洪宇 李帅 王岩松 | 2021 | 中国脊柱脊髓杂志2021，31，4： | 3 |
| 3 | High-frequency spinal cord stimulation produces longlasting analgesic effects by restoring lysosomal function and autophagic flux in the spinal dorsal horn显示文摘High-frequency spinal cord stimulation(HF-SCS) has been established as an effective therapy for neuropathic pain. However, the analgesic mechanisms involved in HF-SCS remain to be clarified. In our study, adult rat neuropathic pain was induced by spinal nerve ligation. Two days after modeling, the rats were subjected to 4 hours of HF-SCS(motor threshold 50%, frequency 10,000 Hz, and pulse width 0.024 ms) in the dorsal horn of the spinal cord. The results revealed that the tactile allodynia of spinal nerve-injured rats was markedly alleviated by HFSCS, and the effects were sustained for 3 hours after the stimulation had ceased. HF-SCS restored lysosomal function, increased the levels of lysosome-associated membrane protein 2(LAMP2) and the mature form of cathepsin D(matu-CTSD), and alleviated the abnormally elevated levels of microtubule-associated protein 1 A/B-light chain 3(LC3)-II and sequestosome 1(P62) in spinal nerve-injured rats. HF-SCS also mostly restored the immunoreactivity of LAMP2, which was localized in neurons in the superficial layers of the spinal dorsal horn in spinal nerve-injured rats. In addition, intraperitoneal administration of 15 mg/kg chloroquine for 60 minutes reversed the expression of the aforementioned proteins and shortened the timing of the analgesic effects of HF-SCS. These findings suggest that HF-SCS may exhibit longlasting analgesic effects on neuropathic pain in rats through improving lysosomal dysfunction and alleviating autophagic flux. This study was approved by the Laboratory Animal Ethics Committee of China Medical University, Shenyang, China(approval No. 2017 PS196 K) on March 1, 2017. | Zhi-Bin Wang Yong-Da Liu Shuo Wang Ping Zhao | 2022 | Neural Regeneration Research2022，17，2： | 2 |
| 4 | 内源性保护在脊髓损伤中的研究进展显示文摘脊髓外伤后,损伤组织会发生一系列病理事件,包括出血性坏死、缺血、水肿、炎症、神经元吞噬等。在成年哺乳动物的脊髓损伤中,缺乏自发的修复机制对损伤修复产生负面影响,所以内源性保护成为中枢神经系统损伤修复的策略。本文结合脊髓损伤病理生理学机制对内源性保护在脊髓损伤中的研究进展做一综述。 | 文应丹 刘矿嫔 | 2022 | 中外医学研究2022，20，31： | 1 |
| 5 | 自噬在兔部分损伤前交叉韧带和内侧副韧带中的差异显示文摘目的:确定兔前交叉韧带和内侧副韧带部分损伤后自噬的存在,并比较损伤后不同时间两者之间自噬的表达差异,探讨其愈合能力差异与自噬的关系。方法:3月龄健康雄性新西兰大白兔18只,随机选取3只作为对照组,其余兔建立前交叉韧带和内侧副韧带部分损伤模型,随机分为5组,各组分别在造模后3 d、1周、2周、4周、6周取材。H-E染色观察损伤部位形态学变化,透射电镜观察损伤部位超微结构变化,免疫印迹检测自噬相关蛋白Beclin 1、LC3Ⅱ/Ⅰ、p62表达水平,RT-PCR检测自噬相关基因Beclin 1、ATG-5 mRNA表达水平。结果:在部分损伤后3 d、1周、2周、4周、6周5个时间点,前交叉韧带和内侧副韧带均未表现出明显的愈合趋势,观察到自噬小体的存在。与对照组相比,自噬相关蛋白Beclin 1、LC3Ⅱ/Ⅰ、p62在前交叉韧带中的高表达更为显著,在内侧副韧带中的表达更早恢复至正常水平,并继续降低;自噬相关基因ATG-5、Beclin 1在前交叉韧带中始终处于高表达状态,峰值出现在1周,内侧副韧带高表达峰值出现在2周,此后逐渐恢复至正常水平。结论:兔前交叉韧带、内侧副韧带部分损伤后自噬相关因子的表达随时间推移,总体呈现先升高后降低的变化趋势,损伤后不同时间点前交叉韧带、内侧副韧带中自噬的表达存在明显差异,推测前交叉韧带损伤后自噬的过度激活可能导致其内源性修复障碍。 | 谷慧凝 韩银河 张明正 李彬 温昱 | 2021 | 解剖学杂志2021，44，3： | 1 |
| 6 | Graphene oxide-composited chitosan scaffold contributes to functional recovery of injured spinal cord in rats显示文摘The study illustrates that graphene oxide nanosheets can endow materials with continuous electrical conductivity for up to 4 weeks. Conductive nerve scaffolds can bridge a sciatic nerve injury and guide the growth of neurons;however, whether the scaffolds can be used for the repair of spinal cord nerve injuries remains to be explored. In this study, a conductive graphene oxide composited chitosan scaffold was fabricated by genipin crosslinking and lyophilization. The prepared chitosan-graphene oxide scaffold presented a porous structure with an inner diameter of 18–87 μm, and a conductivity that reached 2.83 mS/cm because of good distribution of the graphene oxide nanosheets, which could be degraded by peroxidase. The chitosan-graphene oxide scaffold was transplanted into a T9 total resected rat spinal cord. The results show that the chitosan-graphene oxide scaffold induces nerve cells to grow into the pores between chitosan molecular chains, inducing angiogenesis in regenerated tissue, and promote neuron migration and neural tissue regeneration in the pores of the scaffold, thereby promoting the repair of damaged nerve tissue. The behavioral and electrophysiological results suggest that the chitosan-graphene oxide scaffold could significantly restore the neurological function of rats. Moreover, the functional recovery of rats treated with chitosangraphene oxide scaffold was better than that treated with chitosan scaffold. The results show that graphene oxide could have a positive role in the recovery of neurological function after spinal cord injury by promoting the degradation of the scaffold, adhesion, and migration of nerve cells to the scaffold. This study was approved by the Ethics Committee of Animal Research at the First Affiliated Hospital of Third Military Medical University(Army Medical University)(approval No. AMUWEC20191327) on August 30, 2019. | Bing Yang Pang-Bo Wang Ning Mu Kang Ma Shi Wang Chuan-Yan Yang Zhong-Bing Huang Ying Lai Hua Feng Guang-Fu Yin Tu-Nan Chen Chen-Shi Hu | 2021 | Neural Regeneration Research2021，16，9： | 1 |
| 7 | Role of circular RNA expression in the pathological progression after spinal cord injury显示文摘Differential expression of non-coding RNA after traumatic spinal cord injury(TSCI)is closely related to the pathophysiological process.The purposes of this study were to systematically profile and characterize expression of circular RNA(circRNA)in the lesion epicenter of spinal tissues after TSCI,and predict the structure and potential function of the regulatory circRNA/miRNA network.Forty-eight C57BL/6 mice were randomly and equally assigned to two groups:one subjected to TSCI at T8–10 with an Allen’s drop impactor,and a second subjected to laminectomy without TSCI.Spinal cord samples were stained with hematoxylin and eosin,sequenced,and validated.RNA-Seq,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and network analyses(Targetscan and miRanda)were used to predict and annotate the circRNA/miRNA/mRNA network.Luciferase reporter,quantitative reverse transcription polymerase chain reaction,and western blot assays were used to profile expression and regulation patterns of the network in mouse models of TSCI.Hematoxylin-eosin staining revealed severe damage to the blood-spinal cord barrier after TSCI.Differentially expressed circRNA and miRNA profiles were obtained after TSCI;differentially expressed circRNAs,which were abundant in the cytoplasm,were involved in positive regulation of transcription and protein phosphorylation.miR-135b-5p was the most significantly downregulated miRNA after TSCI;circRNAAbca1 and KLF4 were predicted to be its target circRNA and mRNA,respectively.Subsequently,the circAbca1/miR-135b-5P/KLF4 regulatory axis was predicted and constructed,and its targeted binding was verified.After inhibiting circAbca1,GAP43 expression was upregulated.Differential expression of circRNAs might play an important role after TSCI.circAbca1 plays a neuroinhibitory role by targeted binding of the miR-135b-5P/KLF4 axis.The identified circRNA/miRNA/mRNA network could provide the basis for understanding pathophysiological mechanisms underlying TSCI,as well as guide the formulation of related therapeutic strategies.All animal protocols were approved by the Research Ethics Committee of West China Hospital of China(approval No.2017128)on May 16,2017. | Wen-Zhao Wang Jun Li Lei Liu Zheng-Dong Zhang Ming-Xin Li Qin Li Hui-Xu Ma Hai Yang Xiao-Ling Hou | 2021 | Neural Regeneration Research2021，16，10： | 0 |
| 8 | 脊髓损伤中自噬介导的病理机制及其相关干预手段显示文摘脊髓损伤(spinal cord injury,SCI)常导致感觉、运动、括约肌功能的丧失,是导致死亡和长期残疾的主要原因之一[1]。SCI包括原发性损伤和继发性损伤,其中原发性损伤的主要特征包括撞击加持续性压迫、单独冲击与瞬态压缩、分裂、撕裂/横断[2];继发性损伤包括氧化应激、炎症、谷氨酸介导的兴奋性毒性、水肿、坏死、凋亡和自噬[3]。自噬是真核生物特有的依赖于溶酶体的细胞内降解过程,在应对营养缺乏、维持内稳态中发挥重要作用。自噬可以通过调节神经细胞的凋亡而在神经系统疾病中起到保护作用,尤其是SCI。然而,自噬是一把“双刃剑”。 | 吴杏英 胡蓉(综述) 马睿杰(审校) | 2023 | 中国临床神经外科杂志2023，28，5： | 0 |
| 9 | 烯醇化酶抑制剂对脊髓损伤后神经保护的研究进展显示文摘脊髓损伤可导致不可逆的神经元损伤,严重危害患者生命健康,包括其身体和心理状态,为患者及社会带来沉重的负担。在过去三十年中,全球脊髓损伤的患病率从每百万人236例增加到1298例。据统计,全球脊髓损伤发病率每年在25万至50万人之间,在中国,由车祸、建筑和采矿事故引起的脊髓损伤的发生率在过去十年里增加了十倍,其中仅仅不到1%的患者能够在出院时完全恢复神经功能[1-3]. | 周志强 庾红林 解国辉 张钦 | 2022 | 中华危重症医学杂志(电子版)2022，15，2： | 0 |
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