Wang FengLin, Zeng Yan, Liu Xian, Cao JiaJun, Kang ShengNan, Zhou WuShuang, Chen XiaoYing, Liu JingLun, Zhang Dan
Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China; Intensive Care Unit, Chongqing University Central Hospital, Chongqing, 400016, PR China.
Biochem Biophys Res Commun. 2022 May 21;605:162-170. doi: 10.1016/j.bbrc.2022.03.046. Epub 2022 Mar 18.
CGA (Chromofungin, CHR), is a peptide derived from the N-terminus of chromogranin A (CgA), has been proven to inhibit the lipopolysaccharide (LPS)-induced brain injury. However, the underlying mechanism is still unknown. We found that CGA exerted a protective effect on cognitive impairment by inhibiting the destruction of the blood-brain barrier (BBB) in the LPS-induced sepsis mice model. In addition, the hCMEC/D3 cell line was used to establish an in vitro BBB model. Under LPS stimulation, CGA could significantly alleviate the hyperpermeability of the BBB, the destruction of tight junction proteins, and the rearrangement of F-actin. To investigate the underlying mechanism, we used LY294002, a PI3K inhibitor, which partially reduced the protective effect of CGA on the integrity of BBB. Indicating that the PI3K/AKT pathway plays a vital role in the brain-protective function of CGA, which might be a potential therapeutic target for septic brain injury.
嗜铬粒蛋白（Chromofungin，CHR）是一种源自嗜铬粒蛋白A（CgA）N端的肽，已被证明可抑制脂多糖（LPS）诱导的脑损伤。然而，其潜在机制仍不清楚。我们发现，在LPS诱导的脓毒症小鼠模型中，嗜铬粒蛋白通过抑制血脑屏障（BBB）的破坏对认知障碍发挥保护作用。此外，使用hCMEC/D3细胞系建立体外血脑屏障模型。在LPS刺激下，嗜铬粒蛋白可显著减轻血脑屏障的高通透性、紧密连接蛋白的破坏以及F-肌动蛋白的重排。为了研究其潜在机制，我们使用PI3K抑制剂LY294002，其部分降低了嗜铬粒蛋白对血脑屏障完整性的保护作用。表明PI3K/AKT通路在嗜铬粒蛋白的脑保护功能中起关键作用，这可能是脓毒症脑损伤的一个潜在治疗靶点。
