Department of Medical Science, Medical School, Chungnam National University, Daejeon 35015, Korea.
Department of Nephrology, Medical School, Chungnam National University, Daejeon 35015, Korea.
Int J Mol Sci. 2021 Oct 30;22(21):11802. doi: 10.3390/ijms222111802.
Although the cause of neurological disease in patients with chronic kidney disease (CKD) has not been completely identified yet, recent papers have identified accumulated uremic toxin as its main cause. Additionally, omega-3 polyunsaturated fatty acid (ω-3 PUFA) plays an important role in maintaining normal nerve function, but its protective effects against uremic toxin is unclear. The objective of this study was to identify brain damage caused by uremic toxicity and determine the protective effects of ω-3 PUFA against uremic toxin. We divided mice into the following groups: wild-type (wt) sham ( = 8), ω-3 PUFA sham ( = 8), Fat-1 sham ( = 8), ischemia-reperfusion (IR) ( = 20), and ω-3 PUFA+IR ( = 20) Fat-1+IR ( = 20). Brain tissue, kidney tissue, and blood were collected three days after the operation of mice (sham and IR operation). This study showed that Ki67 and neuronal nuclei (NeuN) decreased in the brain of uremic mice as compared to wt mice brain, but increased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. The pro-apoptotic protein expressions were increased, whereas anti-apoptotic protein expression decreased in the brain of uremic mice as compared to wt mice brain. However, apoptotic protein expression decreased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. Furthermore, the brain of ω-3 PUFA-treated uremic mice and uremic Fat-1 mice showed increased expression of p-PI3K, p-PDK1, and p-Akt as compared to the brain of uremic mice. We confirm that uremic toxin damages the brain and causes cell death. In these injuries, ω-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.
尽管慢性肾脏病（CKD）患者神经系统疾病的病因尚未完全明确，但最近的研究表明，蓄积的尿毒症毒素是其主要病因。此外，ω-3 多不饱和脂肪酸（ω-3 PUFA）在维持正常神经功能方面发挥着重要作用，但它对尿毒症毒素的保护作用尚不清楚。本研究旨在明确尿毒症毒素引起的脑损伤，并确定 ω-3 PUFA 对尿毒症毒素的保护作用。我们将小鼠分为以下几组：野生型（wt）假手术组（ = 8）、ω-3 PUFA 假手术组（ = 8）、Fat-1 假手术组（ = 8）、缺血再灌注（IR）组（ = 20）和 ω-3 PUFA+IR 组（ = 20）、Fat-1+IR 组（ = 20）。在手术后三天收集小鼠的脑组织、肾脏组织和血液（假手术和 IR 手术）。本研究表明，与 wt 组相比，尿毒症组小鼠脑内 Ki67 和神经元核（NeuN）减少，但 ω-3 PUFA 治疗的尿毒症组和尿毒症 Fat-1 组小鼠脑内 Ki67 和神经元核（NeuN）增加。与 wt 组相比，尿毒症组小鼠脑内促凋亡蛋白表达增加，抗凋亡蛋白表达减少，但 ω-3 PUFA 治疗的尿毒症组和尿毒症 Fat-1 组小鼠脑内促凋亡蛋白表达减少。此外，与尿毒症组相比，ω-3 PUFA 治疗的尿毒症组和尿毒症 Fat-1 组小鼠脑内 p-PI3K、p-PDK1 和 p-Akt 表达增加。我们证实尿毒症毒素损伤大脑并导致细胞死亡。在这些损伤中，ω-3 PUFA 通过 PI(3)K-Akt 信号通路在神经保护中发挥重要作用。
