摘要
目的评价兰尼碱受体2(RyR2)在老龄大鼠术后认知功能障碍(POCD)中的作用。方法SPF级健康雄性SD大鼠60只,20月龄,体质量600~650 g,采用随机数字表法分为3组(n=20):对照组(C组)、POCD组(P组)和丹曲林组(D组)。P组和D组在七氟烷麻醉下行左侧胫骨骨折闭合复位内固定术制备大鼠POCD模型。D组于术前30 min时尾静脉注射RyR抑制剂丹曲林2 mg/kg。分别于术前1 d和于术后7 d时行Morris水迷宫实验评估大鼠认知功能,并于术后7 d水迷宫实验开始前行旷场实验检测大鼠自发运动功能。水迷宫实验结束后处死大鼠取海马组织,采用Western blot法检测RyR2和裂解的caspase-3的表达,采用流式细胞术检测海马神经元凋亡率和胞浆钙离子浓度,HE染色观察海马CA1区病理学结果。结果3组旷场实验运动速度、路程以及旷场中心停留时间比较差异无统计学意义(P>0.05)。与C组比较,P组术后逃避潜伏期延长,穿越原平台次数减少,海马RyR2和裂解的caspase-3表达上调,神经元凋亡率和胞浆钙离子浓度升高(P<0.05),海马CA1区发生病理学损伤;与P组比较,D组术后时逃避潜伏期缩短,穿越原平台次数增加,海马RyR2和裂解的caspase-3表达下调,神经元凋亡率和胞浆钙离子浓度降低(P<0.05),海马CA1区病理学损伤减轻。结论RyR2激活参与了老龄大鼠POCD的过程,可能与增加钙超载诱发的海马神经元凋亡有关。
Objective To evaluate the role of ryanodine receptor 2(RyR2)in postoperative cognitive dysfunction(POCD)in aged rats.Methods Sixty SPF healthy male Sprague-Dawley rats,aged 20 months,weighing 600-650 g,were divided into 3 groups(n=20 each)using a random number table method:control group(group C),POCD group(group P)and dantrolene group(group D).A rat POCD model was prepared by closed reduction and internal fixation of left tibial fractures with sevoflurane anesthesia in P and D groups.RyR inhibitor dantrolene 2 mg/kg was injected via a tail vein at 30 min before surgery in group D.Morris water maze tests were conducted on day 1 before surgery and day 7 after surgery to evaluate the cognitive function.An open field test was conducted to detect the spontaneous motor function starting from day 7 after surgery.The rats were sacrificed after the end of Morris water maze tests and hippocampal tissues were taken for determination of the expression of RyR2 and cleaved caspase-3(by Western blot),apoptosis rate and cytoplasmic calcium ion concentrations(by flow cytometry)and for microscopic examination of the pathological changes in hippocampal CA1 area(using HE staining).Results There was no significant difference in the speed,distance and duration of stay in the center in the open field test among the three groups(P>0.05).Compared with group C,the escape latency was significantly prolonged after surgery,the number of crossing the original platform was reduced,the expression of RyR2 and cleaved caspase-3 was up-regulated,and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were increased(P<0.05),and the pathological changes were found in the hippocampal CA1 area in group P.Compared with group P,the escape latency was significantly shortened after surgery,the number of crossing the original platform was increased,the expression of RyR2 and cleaved caspase-3 was down-regulated,and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were decreased(P<0.05),and the pathological changes wer
作者
王磊
杨陈祎
汪强
王海云
Wang Lei;Yang Chenyi;Wang Qiang;Wang Haiyun(Clinical College of the Third Center of Tianjin Medical University,Tianjin 300170,China;Tianjin Key Laboratory of Extracorporeal Life Support for Severe Diseases,Tianjin 300170,China;Tianjin Artificial Cell Engineering Technology Research Center,Tianjin 300170,China;Tianjin Hepatobiliary Disease Research Institute,Tianjin 300170,China;Department of Anesthesiology,Cangzhou Central Hospital,Cangzhou 061001,China;Department of Anesthesiology,Nankai University Affiliated Third Central Hospital,Tianjin 300170,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2024年第3期297-301,共5页
Chinese Journal of Anesthesiology
基金
国家自然科学基金面上项目(82071220,82371205)
天津市医学重点学科(专科)建设项目资助(TJYXZDXK-072C)
天津市医学重点学科专项(TJWJ2023XK019)。
关键词
兰尼碱受体钙释放通道
术后认知并发症
老年人
Ranidine receptor calcium release channel
Postoperative cognitive complications
Aged
