长时程亚低温联合复方脑肽节苷脂注射液对颅脑创伤大鼠的神经行为学影响  

Neurobehavioral effects of long-term mild hypothermia combined with compound porcine cerebroside and ganglioside injection after traumatic brain injury in rats

作　　者：赵万勇 徐书刚 王景景 李晓红 孙洪涛 Zhao Wanyong;Xu Shugang;Wang Jingjing;Li Xiaohong;Sun Hongtao(Dept of Neurosurgery,Qilu Hospital of Shandong University Dezhou Hospital,Dezhou 253014;Neurotrauma Repair Research Institute,Characteristic Medical Center of People’s Armed Police Forces,Tianjin 300162;Institute of Medical Engineering and Translational Medicine,Tianjin University,Tianjin 300350)

机构地区：[1]山东大学齐鲁医院德州医院神经外科,德州253014 [2]武警特色医学中心神经创伤修复研究所,天津300162 [3]天津大学医学工程与转化医学研究院,天津300350

出　　处：《安徽医科大学学报》2024年第3期448-454,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:32070791)。

摘　　要：目的探讨长时程亚低温(MHT)联合复方脑肽节苷脂注射液(CPCGI)治疗对颅脑创伤(TBI)大鼠的神经行为学影响及其作用机制。方法36只健康成年雄性SD大鼠随机均分为模型组、MHT组、CPCGI组和MHT+CPCGI组。采用电子可控性皮质损伤装置制备TBI大鼠模型,模型组大鼠腹腔注射等量生理盐水(NS,2 ml/kg)并给予常温(37℃)治疗48 h,MHT组大鼠腹腔注射等量NS并给予亚低温(33.0±1.0)℃治疗48 h,CPCGI组大鼠腹腔注射等量CPCGI(0.6 ml/kg)并给予常温治疗48 h,MHT+CPCGI组大鼠腹腔注射等量CPCGI并给予亚低温治疗48 h;通过神经功能缺损评分评估大鼠的感觉运动功能,Morris水迷宫实验检测大鼠的运动和空间记忆能力,横杆跑动实验和斜坡爬壁实验评估大鼠的运动功能;尼氏染色观察海马神经元数量的变化;采用免疫荧光法检测微管相关蛋白(DCX)和神经元特异性核蛋白(NeuN)表达情况;采用免疫印迹法检测B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)和半胱氨酸蛋白酶-3(Caspase-3)蛋白表达情况。结果与MHT组和CPCGI组相比,MHT+CPCGI组小鼠神经功能缺损评分更低,逃避潜伏期时间更短,跨越平台次数和目标象限所占时间百分比更高,BWT评分更高,爬坡角度更大,神经元数量、DCX和NeuN阳性细胞数量增多,同时Bcl-2表达量增加,Bax和Caspase-3表达量降低(P<0.05)。结论长时程亚低温联合CPCGI治疗通过促进神经再生、抑制细胞凋亡有效改善TBI大鼠的神经行为缺陷,为TBI的临床治疗提供潜在的策略和依据。Objective To investigate the neurobehavioral effects of long-term mild hypothermia(MHT)combined with compound porcine cerebroside and ganglioside injection(CPCGI)after traumatic brain injury(TBI)in rats and its mechanism.Methods 36 healthy adult male SD rats were randomly divided into model group,MHT group,CPCGI group and MHT+CPCGI group.The TBI model was prepared using an electronically controlled cortical injury device.The rats in model group received an intraperitoneal injection of an equal amount of normal saline(NS,2 ml/kg)and were treated at room temperature(37℃)for 48 hours.The rats in MHT group received an intraperitoneal injection of an equal amount of NS and were treated at a slightly low temperature(33.0±1.0)℃for 48 hours.The rats in CPCGI group received an intraperitoneal injection of an equal amount of CPCGI(0.6 ml/kg)and were treated at room temperature for 48 hours.The rats in MHT+CPCGI group received an intraperitoneal injection of an equal amount of CPCGI and were treated at a slightly low temperature for 48 hours.The sensorimotor function of rats was evaluated by modified Neurological Severity Score(mNSS).The motor and spatial memory abilities of rats were detected by Morris water maze test,and the motor function of rats was evaluated by beam walking test(BWT)and inclined-grid climbing test.The number of neurons in hippocampus was observed by Nissl staining and immunofluorescence was used to detect the expression of doublecortin(DCX)and neuronal nuclear antigen antibody(NeuN).Western blot was used to observe the protein expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)and cysteine proteinase-3(Caspase-3).Results Compared with MHT group and CPCGI group,MHT+CPCGI group had a lower mNNS score,shorter escape latency,higher times across the platform and the percentage of time in the target quadrant,higher BWT score and larger climbing angle,increased numbers of neurons,DCX and NeuN positive cells,increased Bcl-2 expression and decreased expression of Bax and Caspase-3.(P<0.0

关 键 词：亚低温 复方脑肽节苷脂 颅脑创伤 神经行为 神经元 凋亡 

分 类 号：R651.1[医药卫生—外科学]