BACKGROUND:Glioma is a highly invasive and drug-resistant malignant primary tumor. Increasing research is focusing on the function of neutrophil extracellular traps (NETs) in glioma progress. We aimed to explore the mechanism of NETs-related genes (NETs-RGs) in glioma to find potential biomarkers for glioma. METHODS:The GSE16011 data set was downloaded from the GEO database, and the gene expression matrix and clinical data of glioma patients were downloaded from the TCGA database, the cbioportal website, and the CGGA database, as the training and validation sets. The NETs-RGs were obtained from previous studies. Subsequently, differential expression analysis, WGCNA, GO enrichment, and GSEA analysis. The risk model was established for Cox, LASSO, survival, and independent prognostic analyses. The CIBERSORT algorithm was used for immune infiltration analysis, and pRRophetic was used for drug sensitivity analysis. Finally, the expression levels of genes were validated by data set, glioma patients' tissue samples, and glioma cells, and evaluating cell biological behavior. RESULTS:A total of 57 differential expression genes between Glioma and Normal samples were obtained. Then, two modules with the highest positive correlation with NETs-RGs by WGCNA, the NETs-RGs were obtained from previous studies. Six candidate genes were obtained for subsequent analysis. Then, we conducted functional enrichment of candidate genes and constructed a glioma prognosis model. The prognosis model was indicated as a good predictor of a patient's glioma risk. These genes were related to immune cells significantly. And drug sensitivity analysis predicted 128 differences in chemotherapy drugs and found that MICALL2 had a significant correlation with multiple drugs. Finally, only NFIL3 had the same trend of significantly high expression levels. Moreover, knockdown NFIL3 can inhibit glioma cell malignant growth, and promote apoptosis. CONCLUSION:Three prognosis-related genes have better prognosis values for glioma patients and may be the potential biomarkers for the treatment of glioma.

Aconitine (AC) ranks among the leading causes of fatal herbal poisoning globally due to its narrow therapeutic window. Although its cardiovascular toxicity has been extensively studied, the precise molecular mechanisms underlying AC-induced central nervous system damage remain unclear. This study aimed to investigate the role of glycerol-3-phosphate dehydrogenase 1 (GPD1) in AC-induced neurotoxicity and to elucidate the underlying metabolic and molecular mechanisms. In a rat model of acute AC poisoning, significant neurological impairments, anxiety-like behaviors, and neuron-specific cell death were observed. Transcriptomic analyses revealed marked metabolic reprogramming following AC exposure, characterized by upregulation of GPD1 and suppression of the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway. Mechanistically, AC disrupted GPD1/PPARγ signaling homeostasis, leading to pathological lipid droplet accumulation and mitochondrial dysfunction, as evidenced by loss of membrane potential and ATP depletion, ultimately resulting in neuronal apoptosis. Notably, targeted knockdown of Gpd1 using shRNA alleviated lipid accumulation, restored mitochondrial function, and significantly improved survival rates and neurological outcomes in poisoned rats. These findings identify the aconitine-GPD1-lipid/mitochondrial axis as a key mechanism underlying AC-induced neurotoxicity and suggest GPD1 as a potential therapeutic target.

Takayasu arteritis (TAK) is a refractory chronic vasculitis of the aorta and its major branches, characterized by unsatisfactory treatment responses and high relapse rates. This review synthesizes current evidence to propose and elaborate a novel pathogenic paradigm: a self-reinforcing "metabolism-epigenetics-inflammation" feedback loop that sustains chronic vascular inflammation in TAK. We detail how immunometabolic reprogramming in immune and vascular wall cells not only meets bioenergetic demands but also generates metabolites (e.g., acetyl-CoA, lactate) that serve as substrates or cofactors for epigenetic modifications. These modifications, in turn, lock in a persistent pro-inflammatory gene expression profile. A central focus is the dissection of the ANK2-MAVS-IL-8 axis, a critical link connecting genetic susceptibility (via ANK2 variants) through mitochondrial dysfunction to sustained, IL-8-driven vascular injury. Building on this mechanistic framework, the review explores the translational potential of emerging biomarker candidates (e.g., IL-8, specific methylation marks) and proposes stratified therapeutic strategies that target distinct nodes within this interactive network, including metabolic drivers, epigenetic stabilizers, and inflammatory effectors. Ultimately, this work provides an integrated conceptual and translational roadmap for advancing precision medicine in TAK.

D-limonene (D-Lim) is a monocyclic monoterpene and the principal component of citrus essential oils; however, the potential mechanisms underlying its neuroprotective effects in traumatic brain injury (TBI) remain incompletely elucidated. By integrating network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation, this study systematically investigated the potential mechanisms through which D-Lim exerts neuroprotective activity. Database analyses and in vivo experiments showed that the anti-inflammatory and neuroprotective effects produced by D-Lim may be related to the p38 MAPK/NF-κB signaling axis and activation of the PI3K/AKT signaling pathway. Molecular docking and RT-PCR experiments indicated interactions between D-Lim and potential target proteins, including Icam1, Kdr, and Dpp4. HE and Nissl staining demonstrated that D-Lim ameliorated TBI-induced neuronal injury. Moreover, D-Lim had no observable effects on major organs and showed no peripheral toxicity, suggesting its favorable applicability for TBI intervention. Following early intervention with D-Lim, the inflammatory response induced by TBI was attenuated, which may be associated with the activation or modulation of the p38 MAPK, PI3K/AKT, and NF-κB p65 signaling pathways. These results indicate a potential acute protective role for D-Lim under prophylactic or early-intervention conditions, provide insights into TBI intervention, and establish a theoretical basis for potential preventive strategies.

Traumatic brain injury (TBI) can cause severe neurological damage. Ferroptosis, a recently discovered form of iron-regulated cell death, is closely associated with TBI. Cannabidiol (CBD) has been demonstrated to exhibit neuroprotective effects. However, the antiferroptotic role of CBD in TBI remains unclear. Investigating whether CBD inhibits ferroptosis after brain injury and its underlying mechanisms is of great significance. We find that ferroptosis can be induced in rats after TBI, and CBD significantly inhibits ferroptosis in TBI rats both in vivo and in vitro. MicroRNAs (miRNAs) are highly expressed in the brain. Differentially expressed miRNAs and mRNAs after TBI are detected by RNA sequencing, and miR-320-3p, Negr1, and the ERK/MEK pathway are screened out due to their strong correlations. The results show that CBD inhibits miR-320-3p expression, increases Negr1 expression, and suppresses the ERK/MEK pathway both in vivo and in vitro. Mechanistically, transfection with miR-320-3p mimics or siNegr1 inhibits the intervention effect of CBD on ferroptosis and the ERK/MEK pathway. Additionally, Negr1 gene silencing reverses the effect of the miR-320-3p inhibitor on ferroptosis factors in PC12 cells, which suggests that miR-320-3p can target Negr1. In conclusion, our findings indicate that CBD can inhibit TBI-induced ferroptosis through the miR-320-3p/Negr1/ERK signaling axis.

The precise treatment and dynamic management of traumatic brain injury pose a substantial challenge to the global healthcare sector. This challenge arises not only from the complex and dynamically evolving pathological microenvironment that follows brain injury and the heterogeneity of the damage but also from the critical importance of maintaining the structural integrity of brain tissue. The intricate pathophysiological milieu subsequent to traumatic brain injury (TBI) hinders the reparative processes, thereby rendering current therapeutic strategies insufficient to satisfy clinical treatment demands. Injectable hydrogels represent a novel and promising biomaterial, offering a groundbreaking platform technology for the repair of traumatic brain injuries. Their distinctive benefits, such as minimally invasive delivery, in situ molding, self-healing capabilities, and adaptability to irregular injury sites, position them as an emerging approach in this field. This study provides a systematic review of the current research landscape and pathogenesis associated with TBI, followed by an in-depth analysis of the application of injectable hydrogels in TBI management. It further explores the use of injectable hydrogels across various TBI models and concludes with a discussion on prospective developmental trajectories. The objective is to elucidate the significance of injectable hydrogels in addressing the limitations of conventional therapies, thereby advancing the implementation of innovative therapeutic strategies for TBI treatment and repair.

Traumatic brain injury (TBI) is a recognized global public health problem. However, there are still limitations in the available therapeutic approaches and a lack of clinically effective drugs. Therefore, an in-depth exploration of the secondary pathological mechanism of TBI and the identification of new effective drugs are urgently needed. Cannabidiol (CBD), a component derived from the cannabis plant, has potential therapeutic effects on neurological diseases and has received increasing attention. However, few reports on CBD intervention in TBI patients exist. Here, we use the Feeney free-fall method to establish a rat TBI model. CBD significantly improves neurological deficit scores, neuronal damage and blood-brain barrier permeability in rats and significantly inhibits the expressions of the brain injury markers S-100β and NSE. Mechanistically, CBD attenuates TBI-induced astrocyte activation, reduces inflammation, and attenuates the expressions of inflammatory prostaglandin system indicators. The use of TG6-10-1 (EP2 inhibitor) and H-89 (PKA inhibitor) indicates that CBD attenuates TBI-induced neurological damage via the PGE 2-EP2-cAMP-PKA signaling pathway. Overall, this research provides a novel drug candidate for the treatment of clinical brain trauma.

Post stroke cognitive impairment (PSCI) is a series of common complications caused by stroke, ranging from mild cognitive impairment to dementia, which seriously affects the recovery and living quality of patients. Currently, the diagnosis of PSCI in the clinic mostly relies on subjective scale assessment, the untimeliness and imprecision of results greatly limit the efficient identification as well as the subsequent diagnosis and treatment of PSCI. With the increasing popularity and optimization of bioassay techniques and equipment, more and more studies have identified potential early warning markers of stroke patients with the development of their cognitive deficits through hematological testing or imaging. Therefore, the application of blood-based biomarkers and imaging techniques is important for the early identification of PSCI. This review focuses on the research progress of the above two testing modalities in PSCI to discuss their vital meanings for disease recognition. It also suggests that the combined application of the two is expected to improve the potential value of early and accurate diagnosis, with a view to providing new ideas for the clinical diagnosis and treatment of PSCI.

Traumatic brain injury (TBI), characterized by structural brain damage caused by external physical shocks, is a significant global health challenge. Autophagy plays an important role in the cellular self-protection mechanism during its pathological progression. Traditional Chinese medicine (TCM) has a long history and unique advantages in neuroprotection. This review summarizes the key markers of autophagy and the relevant signaling pathways involved in autophagy in TBI, mainly including the PI3K/Akt/mTOR, AMPK/mTOR, Nrf2, TLR4 signaling pathways, and the endoplasmic reticulum stress autophagy axis. In addition, this paper summarizes the recent advances in TCM approaches in TBI autophagy treatment, such as terpenoids, flavonoids, polyphenols, alkaloids, and carotenoids, which are active components of TCM, as well as acupuncture nonpharmacological therapies.

BackgroundThis study assessed the diagnostic capabilities of eight inflammatory biomarkers in first-episode schizophrenia (SCZ), bipolar disorder (BD), and depression (D), examining their differential expression across these psychiatric disorders. The markers studied include neutrophils/lymphocyte ratio (NLR), aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), lymphocytes/high-density lipoprotein (HDL) ratio (LHR), monocytes/HDL ratio (MHR), neutrophils/HDL ratio (NHR), and platelets/HDL ratio (PHR).MethodsWe conducted a retrospective observational study involving 335 individuals with SCZ, 68 with BD, 202 with D, and 282 healthy controls (C) to evaluate hematologic parameters from untreated patients and controls.ResultsSignificant differences in biomarker levels were found between patient groups and controls. Logistic regression analysis indicated that NHR and MHR (p < 0.001), as well as LHR and NLR (p < 0.01), were predictive factors for SCZ. MHR was a predictive factor for BD (p < 0.05). NHR (p < 0.01) and MHR (p < 0.001) were predictive factors for distinguishing between D and C. The area under the curve (AUC) value of the NHR + MHR + NLR composite index model for the SCZ group was 0.846 (p < 0.001). In the BD group, the AUC value for the MHR was 0.816 (p < 0.001). The D group’s combined AUC value of NHR + MHR was 0.824 (p < 0.001).ConclusionThis study highlights the diagnostic value of inflammatory biomarkers in distinguishing SCZ, BD, and D based on their differential expression.

Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca2+ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.

Bakuchiol (Bak) possesses a protective effect in acute lung injury (ALI). Nonetheless, the molecular processes that regulate the protective activity of Bak in ALI remain elusive. Lipopolysaccharide (LPS)–treated rats and RLE-6TN cells were used as the ALI models in vivo and in vitro to investigate the function and mechanism of Bak. Rats were divided into four groups: control, LPS, LPS + Bak (30 mg/kg), and LPS + Bak (60 mg/kg). RLE-6TN cells were assigned into four groups: control, LPS, LPS + Bak (10 µM), and LPS + Bak (20 µM). Myeloperoxidase (MPO) and 4-hydroxy-2-nonenal (4-HNE) levels were detected by immunohistochemistry (IHC). The levels of TNF-α, IL-6, and IL-1β were quantified by ELISA. Apoptosis was analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were assayed to evaluate oxidative stress. In LPS-induced rats, Bak attenuated pathological injury, lung wet/dry weight ratio, MPO expression, and protein concentration and cell number in bronchial alveolar lavage fluid (BALF). Bak decreased the secretion of TNF-α, IL-6, and IL-1β in BALF. Bak reduced MDA content and 4-HNE expression, and increased SOD and GSH-Px activities in lung tissues. Bak also repressed pulmonary apoptosis by decreasing Bax expression and enhancing Bcl-2 expression. In LPS-treated RLE-6TN cells, Bak downregulated the mRNA levels of TNF-α, IL-6, and IL-1β and inhibited the protein expression of iNOS and COX2. Bak decreased MDA level and ROS production and increased SOD and GSH-Px activities. Bak also suppressed cell apoptosis, reduced Bax expression, and increased Bcl-2 expression. Moreover, Bak decreased the expression of TLR4, MyD88, p-IκBα, and p-p65. Additionally, Bak inhibited Keap1 expression and increased Nrf2 and HO-1 levels. Bak protects against LPS-induced inflammation, oxidative stress, and apoptosis in ALI by regulating TLR4/MyD88/NF-κB and Keap1/Nrf2/HO-1 pathways.

目的 观察创伤性脑损伤(traumatic brain injury,TBI)大鼠脑组织中水通道蛋白4(aquaporin 4,AQP4)的表达及其时程变化规律,探讨大麻二酚(cannabidiol,CBD)对AQP4的干预作用.方法 采用改良"Feeney自由落体法"制备大鼠TBI模型,然后随机分为致伤后8 h、1 d、2 d、3 d、5 d、7 d 6个损伤组和6个CBD干预组,另设正常对照组、假手术组.采用免疫荧光单标染色和Western blotting实验观察各组大鼠损伤侧皮质区AQP4蛋白表达情况.结果 免疫荧光染色结果显示,与假手术组相比,TBI致伤后AQP4阳性表达随时间推移逐渐增高,3 d达到高峰,5 d、7 d有所下降(P＜0.05),但仍高于假手术组;CBD干预后1 d、2 d、3 d和5 d的AQP4阳性表达均下降(P＜0.05).Western blotting实验结果显示,与假手术组相比,TBI致伤后8h、l d、2d、3 d的AQP4蛋白表达水平均有所增加(P＜0.05);CBD干预后AQP4蛋白表达水平较TBI组均有所下降(P＜0.05).结论 TBI可引起AQP4表达升高,3 d达到高峰,而CBD能够抑制AQP4过表达,以1 d、2d、3 d干预效果最为明显.

Aconitine is a crucial toxic component in Chinese herbal medicines such as Aconitum, Aconitum coreanum, and Aconitum soongaricum. The poisoning symptoms of the central nervous system and cardiovascular system caused by it are relatively common in China, and there are many studies on cardiovascular system diseases caused by aconitine. However, the specific mechanism of neurotoxicity induced by aconitine is still unclear. This study explored the effect and mechanism of mitochondrial calcium uniporter on mitochondrial energy metabolism disorder in aconitine poisoning hippocampal neurons. The results showed that after treatment with 400μmol/L aconitine, mitochondrial energy metabolism was abnormal in rat hippocampal neuron cells, the expression of MCU in mitochondria was up-regulated, calcium overload in mitochondria, ATP production decreased, and mitochondrial membrane potential Changes, increased expression of the apoptosis gene Cleaved-Caspase-3. After treatment with the MCU agonist spermine, mitochondrial energy metabolism was significantly abnormal, and cell apoptosis was increased considerably. However, pretreatment with calcium ion channel inhibitor Ruthenium Red (RR) effectively promoted the generation of ATP, thereby improving mitochondrial energy metabolism disorders and reducing cell apoptosis. These results suggest that aconitine induces mitochondrial energy metabolism dysfunction in hippocampal neurons, which may be related to the increased expression of MCU.

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BCA T1 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 explore the mechanism of dexmedetomidine (DEX) regulating microglial (MG) polarization and neuroinflammation after traumatic brain injury (TBI) in rats.Methods:Forty-two adult male SD rats were randomly (random number) divided into the sham group, TBI group, TBI+DEX group (further divided into 1 d, 3 d and 7 d subgroups), TBI+NF-κB inhibitor (pyrrolidine dithiocarbamate, PDTC) group and TBI+DEX+PDTC group, with 6 animals in each group. The rat TBI model was established according to the modified Feeney free fall method. PDTC was intraperitoneally injected 1 h after modeling with a dose of 100 mg/kg, and DEX was intraperitoneally injected 2 h after modeling with a dose of 100 μg/kg. Modified neurological severity score (mNSS) was used to evaluate rat neurological function, ELISA was used to detect serum inflammatory factors, and rats’ damaged cortex was collected to detect the phenotype markers of MG and protein expressions of MyD88 and NF-κB p65, and immunofluorescence staining was used to observe the expression and nuclear entry of NF-κB p65 in MG in injured cortex. One-way and two-way ANOVA were used to compare the measurement data among multiple groups.Results:Compared with the sham group, the mNSS score was significantly higher in the TBI group, and DEX treatment significantly decreased the mNSS score of TBI rats ( P<0.05). ELISA and Western blot results showed that in the TBI group, the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β in serum and M1 phenotype marker (TNF-α, IL-1β) in brain were increased, the expression of anti-inflammatory factor IL-10 in serum and M2 phenotype markers (arginase-1 and IL-10) in brain were decreased ( P<0.05), and DEX downregulated the expression of TNF-α, IL-1β in serum and M1 phenotype markers in brain, while upregulated the level of L-10 in serum and the M2 phenotype marker in brain ( P<0.05). In addition, the expression of MyD88 and the nuclear translocation of NF-κB p65 were inhibited in the DEX group, and this effect could be enhanced by PDTC. Conclusions:DEX modulates MG activation in TBI rats by inhibiting NF-κB nuclear translocation and reduces neuroinflammation.

目的 探讨PBL联合数字化微课在生殖医学本科生教学中的应用,可为提高生殖医学人才培养质量提供参考.方法 以389名昆明医科大学临床医学专业和生殖医学选修课班学生为研究对象,授课后收集学生在医学知识获取、医学思维培养、自主学习和实践能力等评价指标,可能影响授课效果的因素,并对结果进行评价分析.结果 该方法授课后学生在医学知识获取和医学思维培养,自主学习和实践能力方面有较明显优势,且分组结果存在显著差异(P<0.05).但有知识获取途径有限和课程准备时间长等问题.结论 PBL联合数字化微课是适合生殖医学教学的有效授课模式,有助于学生知识获取和能力提升,可推广应用.

目的 探讨创伤性脑损伤的流行病学特征,为疾病诊疗提供依据,提高创伤性脑损伤的综合救治.方法 采取回顾性研究的方法,查阅昆明医科大学第一附属医院病案室创伤性脑损伤患者,在院救治的一系列病例资料共3 552例,其中2 044例为昆明医科大学第一附属医院住院患者,1 508例为外院转入患者,主要收集和进行统计学分析的资料有性别、年龄、职业、创伤原因、治疗方法及预后.结果 男性患者占75.08％,女性患者占24.91％,男患者与女患者所占比是3.01 ∶ 1,且各个年龄段的TBI男性明显高于女性,差异有统计学意义(P＜0.05).其中主要为中年患者(41.66±15.72)岁;农民工是发生创伤性脑损伤最多的职业;创伤发生原因排名前3的是车祸伤45.27％、高处坠落伤18.92％与跌倒伤17.57％;急性颅脑损伤是最主要的致死因素.结论 所收集的云南部分地区的病例资料分析提示:创伤性脑损伤患者主要以从事体力活动的中年男性为主,发病原因居于前3的依次是车祸伤、坠落伤与跌倒伤,减少TBI的发生和提高TBI的紧急救治成为了急危重症疾病的重点.

目的 探索创伤性脑损伤(traumatic brain injury,TBI)大鼠模型中铁死亡的发生及与其密切相关的基因.方法 将SD大鼠随机分为Sham组和TBI组,采用普鲁士蓝(Perl′s)染色和透射电镜观察TBI大鼠脑组织发生铁沉积和铁死亡的情况;转录组测序初步鉴定TBI大鼠脑组织差异表达基因(differentially express genes,DEGs),将DEGs与数据集GSE111452比较,选择共有的DEGs,再将共有DEGs与铁死亡数据库比对,最终筛选出与铁死亡密切相关的DEGs;最后,通过荧光定量PCR检测大鼠脑组织样本中DEGs的mRNA相对表达量.结果 Perl′s染色结果显示,TBI大鼠脑组织损伤周围区域铁离子沉积现象较Sham组明显;电镜结果显示,TBI大鼠脑组织中神经元形态改变,线粒体萎缩变小,基质颜色变深,膜增厚致密度高,部分外膜模糊并破损,伴有内嵴扩张、减少.测序和信息学分析结果显示,与Sham组比较,TBI大鼠脑组织共有2786个DEGs,与GSE111452数据集交集后发现241个共有DEGs,再与铁死亡相关基因库比对,发现4个与铁死亡相关的DEGs(Slc7a5、Rb1、Fancd2和Pebp1);PCR检测结果显示,TBI大鼠脑组织中Slc7a5和Fancd2基因的mRNA表达水平显著升高,Rb1基因的mRNA表达水平也有升高趋势,但与Sham组比较差异无统计学意义(P>0.05),Pebp1基因的mRNA表达水平显著下降(P<0.05).结论 TBI大鼠脑组织发生了铁死亡,可能与Slc7a5、Rb1、Fancd2和Pebp1基因在TBI大鼠脑组织的差异表达有关.

Cannabidiol is a natural herbal medicine known to protect the brain from traumatic brain injury (TBI). Here, a TBI rat model was established, with cannabidiol administered intraperitoneally at doses of 5, 10, or 20 mg/kg, 30 min before surgery and 6 h after surgery until sacrifice. Brain water content, body weight, and modified neurological severity scores were determined, and enzyme-linked immunosorbent assay, immunofluorescence staining, hematoxylin and eosin staining, Nissl staining, Evans-blue dye extravasation, and western blotting were performed. Results showed that cannabidiol decreased the number of aquaporin-4-positive and glial fibrillary acidic protein-positive cells. Cannabidiol also significantly reduced the protein levels of proinflammatory cytokines (TNF-alpha and IL-1 beta) and significantly increased the expression of tight junction proteins (claudin-5 and occludin). Moreover, cannabidiol administration significantly mitigated water content in the brain after TBI and blood-brain barrier disruption and ameliorated the neurological deficit score after TBI. Cannabidiol administration improved the integrity and permeability of the blood-brain barrier and reduced edema in the brain after TBI.