Mascarenhas Desmond D
Mayflower Organization for Research & Education, Sunnyvale, CA, USA.
Transporin, Inc., Sunnyvale, CA, USA.
Scars Burn Heal. 2020 Aug 11;6:2059513120939443. doi: 10.1177/2059513120939443. eCollection 2020 Jan-Dec.
Survivors of severe burns suffer lifetime neuroinflammatory consequences manifested by higher incidence of major depression and neurodegenerative disease. In a scald model, nephrilin peptide has previously been shown to protect rats from loss of lean body mass, kidney function and glycaemic control, complications that have also been shown to endure in burn patient populations. Nephrilin's mechanism of action has been suggested to involve protection from excessive oxidative stress.
Using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) amplification of transcripts in total RNA extracted from dorsal root ganglia of male rats 14 days after exposure to thermal insult, we query the relative levels of expression of 34 genes believed to be associated with oxidative stress biology in the central nervous system (CNS). We use these data to explore the central role of oxidative stress in astrogliosis, immunosuppression and mitochondrial homeostasis.
Rats that received nephrilin treatment (4 mg/kg by subcutaneous bolus injection once daily for seven days after scald injury) showed significantly reduced elevations in gene expression of some key genes such as NOX2, GFAP, AQP4 and RAC1, but not of others such as NOX4, STEAP4, ARG1 and CCL2.
The implications of these data with reference to nephrilin's potential clinical utility for mitigating the enduring effects of burn trauma on the CNS are discussed. Nephrilin reduces the expression of some genes implicated in neurodegeneration after burn insult.
Nephrilin peptide is a novel treatment for short- and long-term systemic effects of burn trauma. This study measures the capability of nephrilin to address post-traumatic neurodegenerative disease by looking at the expression of genes in the central nervous system, in a rat scald model. Nephrilin appears to have beneficial effects by reducing the expression of some key genes known to be relevant in neurodegenerative processes, but not others.
严重烧伤幸存者会遭受终生神经炎症后果，表现为重度抑郁症和神经退行性疾病的发病率更高。在烫伤模型中，此前已证明肾裂素肽可保护大鼠避免瘦体重、肾功能和血糖控制丧失，这些并发症在烧伤患者群体中也持续存在。肾裂素的作用机制被认为涉及防止过度氧化应激。
利用定量逆转录聚合酶链反应（qRT-PCR）扩增雄性大鼠热损伤14天后从背根神经节提取的总RNA中的转录本，我们探究了34个被认为与中枢神经系统（CNS）氧化应激生物学相关的基因的相对表达水平。我们利用这些数据来探索氧化应激在星形胶质细胞增生、免疫抑制和线粒体稳态中的核心作用。
接受肾裂素治疗的大鼠（烫伤损伤后每天皮下推注注射一次4 mg/kg，持续7天）显示，一些关键基因如NOX2、GFAP、AQP4和RAC1的基因表达升高明显降低，但其他基因如NOX4、STEAP4、ARG1和CCL2则不然。
讨论了这些数据对于肾裂素减轻烧伤创伤对中枢神经系统持久影响的潜在临床效用的意义。肾裂素可降低烧伤损伤后一些与神经退行性变相关基因的表达。
肾裂素肽是一种治疗烧伤创伤短期和长期全身影响的新型疗法。本研究通过观察大鼠烫伤模型中枢神经系统中基因的表达，测量了肾裂素解决创伤后神经退行性疾病的能力。肾裂素似乎通过降低一些已知与神经退行性过程相关的关键基因的表达而产生有益效果，但对其他基因则不然。
