Yu Guangna, Sun Xingyuan, Li Li, Huang Lijuan, Liu Hongbin, Wang Shuying, Ren Zhanjun, Zhang Yanjiao
Department of Physical Examination, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China.
Director's Office, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China.
Exp Ther Med. 2020 Mar;19(3):2282-2290. doi: 10.3892/etm.2019.8403. Epub 2019 Dec 31.
Although higher serum level of cystatin C (CysC) was observed in patients with cerebral microbleeds, its associated role in the disease has not been elucidated. In this work, a rat model of cerebral microbleeds was created with the aim of investigating effects of CysC on cognitive function in rats with cerebral microbleeds and the underlying mechanism. Serum samples of patients with cerebral microbleeds and healthy people of the same age were collected. Levels of cystatin C expression in these samples were measured using CysC kits. Moreover, 48 spontaneously hypertensive rats (SHRs) bred under specific pathogen-free (SPF) conditions were randomly divided into 4 groups: sham surgery control group (sham), model group (CMB), model + empty vector control group (CMB + vehicle), and model + cystatin C overexpression group (CMB + CysC). Expression levels of CysC in hippocampus of rats in each group were measured by western blot analysis. The Y-maze was used to evaluate cognitive function of rats. Hippocampal long-term potentiation (LTP) in rats was assessed by the electrophysiological assay. Alterations in levels of p-ERK1/2 and p-synapsin Ia/b proteins associated with cognitive function were identified by western blot analysis. The serum levels of CysC in patients with cerebral microbleeds were significantly upregulated (P<0.001). After injection of CysC, its expression levels in rat hippocampus were significantly increased (P<0.001), which enhanced the decline in learning and memory function, as well as the decrease of LTP in the rat model of cerebral microbleeds (P<0.001). Western blot results showed that injection of CysC further reduced the levels of p-ERK1/2 and p-synapsin Ia/b in the rat model of microbleeds (P<0.001). CysC was up regulated in serum of patients with cerebral microbleeds. It promoted cognitive dysfunction in rats with microbleeds by inhibiting ERK/synapsin Ia/Ib pathway.
虽然在脑微出血患者中观察到血清胱抑素C（CysC）水平较高，但其在该疾病中的相关作用尚未阐明。在这项研究中，创建了脑微出血大鼠模型，旨在研究CysC对脑微出血大鼠认知功能的影响及其潜在机制。收集脑微出血患者和同龄健康人的血清样本。使用CysC试剂盒测量这些样本中胱抑素C的表达水平。此外，将48只在无特定病原体（SPF）条件下饲养的自发性高血压大鼠（SHR）随机分为4组：假手术对照组（假手术组）、模型组（CMB）、模型+空载体对照组（CMB+载体）和模型+胱抑素C过表达组（CMB+CysC）。通过蛋白质免疫印迹分析测量每组大鼠海马中CysC的表达水平。采用Y迷宫评估大鼠的认知功能。通过电生理测定评估大鼠海马的长时程增强（LTP）。通过蛋白质免疫印迹分析确定与认知功能相关的p-ERK1/2和p-突触素Ia/b蛋白水平的变化。脑微出血患者的血清CysC水平显著上调（P<0.001）。注射CysC后，其在大鼠海马中的表达水平显著增加（P<0.001），这加剧了脑微出血大鼠模型中学习和记忆功能的下降以及LTP的降低（P<0.001）。蛋白质免疫印迹结果显示，注射CysC进一步降低了微出血大鼠模型中p-ERK1/2和p-突触素Ia/b的水平（P<0.001）。CysC在脑微出血患者血清中上调。它通过抑制ERK/突触素Ia/Ib途径促进微出血大鼠的认知功能障碍。
