摘要
探究负载姜黄素(Cur)的间充质干细胞(MSCs)外泌体(Exos)对七氟烷(Sev)诱导的老年大鼠认知障碍和神经损伤的影响。SD老龄大鼠分为对照组、Sev组、Exos组、Cur组和Exos-Cur组,每组10只。Morris水迷宫用于检测大鼠认知功能,HE染色用于观察大鼠海马病理形态变化,尼氏染色用于观察大鼠海马神经元损伤,TUNEL用于检测大鼠海马细胞凋亡水平,采用ELISA检测大鼠海马组织中肿瘤坏死因子(TNF)-α和白介素(IL)-1β水平,Western blot用于检测大鼠海马组织中C-X-C基序趋化因子配体13(CXCL13)和C-X-C基序趋化因子受体5(CXCR5)蛋白表达。与对照组相比,Sev组老年大鼠逃避潜伏期显著升高,穿越平台次数显著降低(P<0.05),大鼠海马病理损伤加重且神经元数量减少,海马细胞凋亡水平显著升高(P<0.05),海马组织中TNF-α和IL-1β水平以及CXCL13和CXCR5蛋白表达水平显著升高(P<0.05);与Sev组相比,Exos组、Cur组和Exos-Cur组老年大鼠逃避潜伏期显著降低,穿越平台次数显著升高(P<0.05),大鼠海马病理损伤改善且神经元数量增多,海马细胞凋亡水平显著降低(P<0.05),海马组织中TNF-α和IL-1β水平以及CXCL13和CXCR5蛋白表达水平显著降低(P<0.05)。研究证实,负载姜黄素的间充质干细胞外泌体改善七氟烷诱导的老年大鼠认知障碍和神经损伤的机制可能与抑制CXCL13/CXCR5信号通路介导的促炎细胞因子释放有关。
To explore the effects of exosomes(Exos)of mesenchymal stem cells(MSCs)loaded with curcumin(Cur)on cognitive impairment and nerve injury induced by sevoflurane(Sev)in aged rats,Sprague-Dawley(SD)aged rats were divided into the control group,Sev group,Exos group,Cur group and Exos-Cur group,with 10 rats in each group.Morris water maze was used to detect the cognitive function of rats,HE staining was used to observe the pathological changes of rat hippocampus,Nissl staining was used to observe the damage of rat hippocampal neurons,TUNEL was used to detect the apoptosis level of rat hippocampal cells,ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in rat hippocampus,and Western blot was used to detect protein expressions of C-X-C motif chemokine ligand 13(CXCL13)and C-X-C motif chemokine receptor 5(CXCR5)in rat hippocampus.Compared with the control group,the escape latency of aged rats in Sev group was significantly increased,and the times of crossing platforms was significantly decreased(P<O.05).The pathological damage of hippocampus was aggravated,the number of neurons was reduced,the level of apoptosis of hippocampus cells was significantly increased(P<0.05),the levels of TNF-αand IL-1βand the expression levels of CXCL13 and CXCR5 proteins in hippocampus were significantly increased(P<0.05).Compared with Sev group,the escape latency of the aged rats in Exos group,Cur group and Exos-Cur group was significantly reduced,the times of crossing the platform were significantly increased(P<0.05),the pathological damage of hippocampus was improved,the number of neurons was increased,the level of apoptosis in hippocampus was significantly reduced(P<0.05),the levels of TNF-αand IL-1βand the expression levels of CXCL13 and CXCR5 proteins in hippocampus were significantly reduced(P<0.05).This study confirms that the mechanism of curcumin-loaded mesenchymal stem cell exosomes improving sevoflurane-induced cognitive impairment and nerve injury in aged rats may be related to inhibiting the release of pro-inflammatory cytokines mediated by CXCL13/CXCR5 signaling pathway.
作者
张晓敏
谢昕
杜薇
张艳梅
ZHANG Xiaomin;XIE Xin;DU Wei;ZHANG Yanmei(Department of Anesthesiology,Liaoning Cancer Hospital&Institute Cancer Hospital of China Medical University,Liaoning 110042,China)
出处
《药物生物技术》
2025年第6期727-732,共6页
Pharmaceutical Biotechnology
基金
辽宁省自然基金(No.2023-BS-044)。
