Department of Anesthesiology & Laboratory of Pediatric Clinical Pharmacology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Center for Brain Science, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
BMC Neurosci. 2022 Nov 16;23(1):66. doi: 10.1186/s12868-022-00753-5.
Esketamine upregulates Zn-dependent matrix metalloproteinase 9 (MMP9) and increases the neuronal apoptosis in retinal ganglion cell layer during the early development. We aimed to test whether albumin can alleviate esketamine-induced apoptosis through downregulating Zn-dependent MMP9.
We investigate the role of Zn in esketamine-induced neuronal apoptosis by immunofluorescence. MMP9 protein expression and enzyme activity were investigated by zymography in situ., western blot and immunofluorescence. Whole-mount retinas from P7 Sprague-Dawley rats were used.
We demonstrated that esketamine exposure increased Zn in the retinal GCL during the early development. Zn-dependent MMP9 expression and enzyme activity up-regulated, which eventually aggravated apoptosis. Albumin effectively down-regulated MMP9 expression and activity via binding of free zinc, ultimately protected neurons from apoptosis. Meanwhile albumin treatment promoted activated microglia into multi-nucleated macrophagocytes and decreased the inflammation.
Albumin alleviates esketamine-induced neuronal apoptosis through decreasing Zn accumulation in GCL and downregulating Zn-dependent MMP9.
在视网膜神经节细胞层的早期发育过程中，依托咪酯上调 Zn 依赖性基质金属蛋白酶 9（MMP9）并增加神经元凋亡。我们旨在通过下调 Zn 依赖性 MMP9 来测试白蛋白是否可以减轻依托咪酯诱导的凋亡。
我们通过免疫荧光法研究 Zn 在依托咪酯诱导的神经元凋亡中的作用。通过原位酶谱、western blot 和免疫荧光法研究 MMP9 蛋白表达和酶活性。使用 P7 斯普拉格-道利大鼠的全视网膜。
我们表明，依托咪酯暴露在早期发育过程中增加了视网膜 GCL 中的 Zn。Zn 依赖性 MMP9 表达和酶活性上调，最终加重了细胞凋亡。白蛋白通过结合游离锌有效地下调 MMP9 的表达和活性，最终保护神经元免于凋亡。同时，白蛋白处理促进激活的小胶质细胞转化为多核巨细胞，并减少炎症。
白蛋白通过减少 GCL 中的 Zn 积累和下调 Zn 依赖性 MMP9 来减轻依托咪酯诱导的神经元凋亡。
