HIF-1α抑制剂对脓毒症相关性脑病大鼠认知功能及神经细胞自噬的影响  

Effects of HIF-1α inhibitor on cognitive function and neuronal autophagy in rats with sepsis-associated encephalopathy

作　　者：何浩[1] 杨静[1] 谭波 赵珂[1] 陈丽[1] HE Hao;YANG Jing;TAN Bo;ZHAO Ke;CHEN Li(Department of Critical Care Medicine,Affiliated Hospital of Chuanbei Medical College,Nanchong 637000,China)

机构地区：[1]川北医学院附属医院重症医学科,四川南充637000

出　　处：《生物技术》2023年第2期232-238,共7页Biotechnology

基　　金：川北医学院附属医院院级科研课题(2020JC002)。

摘　　要：[目的]探讨HIF-1α抑制剂对脓毒症相关性脑病(SAE)大鼠认知功能及神经细胞自噬的影响。[方法] 48只SPF级健康Wistar大鼠,随机分为空白组、假手术组、脓毒症非SAE组、SAE组、脓毒症非SAE+HIF-1α特异性抑制剂(YC-1)组、SAE+YC-1组,每组8只。采用盲肠结扎穿孔术(CLP)诱导SAE大鼠模型,在行CLP术前24h经股静脉插管缓慢注射YC-1(10 mg/kg溶解于二甲基亚砜)。CLP术后36 h,进行新物体识别试验、悬尾试验、旷场试验,并取海马区脑组织标本,采用HE染色观察海马区脑组织病理变化,透射电镜观察神经细胞自噬变化,Western Blotting检测海马区脑组织Beclin-1、LC3-Ⅰ、LC3-Ⅱ、HIF-1α蛋白表达。[结果]与空白组相比,脓毒症非SAE组、SAE组、脓毒症非SAE+YC-1组、SAE+YC-1组明显降低大鼠的记忆能力和探索能力,明显升高海马区脑组织Beclin-1蛋白表达及明显降低LC3-I蛋白表达(P<0.05),脓毒症非SAE组和SAE组海马区脑组织病理损伤明显。与SAE组比较,HIF-1α抑制剂处理可明显增加SAE大鼠接触次数,改善海马区脑组织病理变化,降低自噬相关蛋白Beclin-1、LC3-II表达,升高LC3-I蛋白表达,但差异无统计学意义(P>0.05)。[结论] HIF-1α抑制剂可明显改善SAE大鼠的认知功能障碍和情绪异常,改善海马区脑组织病理变化,缓解细胞自噬。[Objective]To investigate the effects of HIF-1α inhibitor on cognitive function and neuronal autophagy in rats with sepsis-associated encephalopathy(SAE).[Method]Forty-eight SPF-grade healthy Wistar rats were randomly divided into control group,sham-operated group,septic non-SAE group,SAE group,septic non-SAE + HIF-1α specific inhibitor(YC-1) group,SAE + YC-1 group,8 rats in each group.The rat model of SAE was induced by cecal ligation and puncture(CLP),and YC-1(10 mg/kg dissolved in dimethyl sulfoxide) was slowly injected via femoral vein cannula 24 h before performing CLP.At 36 h after CLP,new object recognition test,hanging tail test,and open field test were performed,and brain tissue specimens were taken from the hippocampal region to observe the histopathological changes in the hippocampal region by HE staining,the autophagic changes in neuronal cells by transmission electron microscopy,and the expression of Beclin-1,LC3-I,LC3-Ⅱ,and HIF-1α proteins in the hippocampal region by Western Blotting.[Result] Compared with the control group,the sepsis non-SAE group,SAE group,sepsis non-SAE+YC-1 group,and SAE+YC-1 group significantly decreased the memory ability and exploration ability of rats,significantly increased Beclin-1 protein expression and significantly decreased LC3-I protein expression in hippocampal brain tissue(P<0.05),and the hippocampal histopathological damage was obvious in the sepsis non-SAE group and SAE group.Compared with the SAE group,HIF-1α inhibitor treatment significantly increased the number of exposures in SAE rats,improved the histopathological changes in the hippocampal region,decreased the expression of autophagy-related proteins Beclin-1 and LC3-Ⅱ,and increased the expression of LC3-Ⅰprotein,but the differences were not statistically significant(P>0.05).[Conclusion]HIF-1α inhibitor significantly improved cognitive dysfunction and mood abnormalities,ameliorated brain histopathological changes in the hippocampus and alleviated cellular autophagy in SAE rats.

关 键 词：脓毒症相关性脑病 HIF-1α抑制剂 细胞自噬 认知功能 

分 类 号：R742[医药卫生—神经病学与精神病学]