摘要
目的探讨利拉鲁肽通过调控Wnt/β-catenin信号通路对急性脊髓损伤大鼠神经保护作用的机制。方法60只SD大鼠随机选取15只作为假手术组(仅接受T9~T10椎板切除术),其余45只大鼠采用改进Allens技术建立急性脊髓损伤模型。脊髓损伤模型建立成功后,随机分为模型组、利拉鲁肽组和利拉鲁肽+XAV939组,各15只。在脊髓损伤后的14 d内,假手术组和模型组大鼠每天皮下注射50 mg/kg生理盐水,利拉鲁肽组大鼠每天皮下注射50μg/kg利拉鲁肽,利拉鲁肽+XAV939组大鼠每天皮下注射50μg/kg利拉鲁肽和0.4 mg/kg XAV939(一种Wnt/β-catenin信号通路的小分子抑制剂)。于术前、干预第7天、第14天时,采用BBB评分法对大鼠下肢运动功能进行评估。第14天采用蛋白质免疫印迹(Western blot)和免疫组化分析β-连环蛋白(β-catenin)、胱天蛋白酶3(caspase-3)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)蛋白表达水平。第14天采用HE和尼氏染色观察大鼠脊髓组织神经细胞变化。结果术前各组间BBB评分无差异。干预第7天、第14天时,模型组、利拉鲁肽组及利拉鲁肽+XAV939组的BBB评分相较于术前显著降低,并显著低于假手术组(P<0.05),利拉鲁肽组的BBB评分显著高于模型组、利拉鲁肽+XAV939组(P<0.05),而模型组与利拉鲁肽+XAV939组的BBB评分比较差异无统计学意义(P>0.05)。模型组、利拉鲁肽组和利拉鲁肽+XAV939组大鼠脊髓前角尼氏染色阳性细胞数量明显少于假手术组(P<0.05);与模型组和利拉鲁肽+XAV939组相比,利拉鲁肽组尼氏染色阳性细胞的数量显著增加(P<0.05);而模型组与利拉鲁肽+XAV939组尼氏染色阳性细胞数量相比差异无统计学意义(P>0.05)。Western blot分析结果显示,相较于假手术组,模型组β-catenin显著增高(P<0.05);与模型组相比,利拉鲁肽组β-catenin显著升高(P<0.05);与利拉鲁肽组相比,利拉鲁肽+XAV939组β-catenin显著降低(P<0.05)。与假手术组相比
Objective To explore the mechanism of the neuroprotective effects of liraglutide on acute spinal cord injury rats by regulating the Wnt/β-catenin signaling pathway.Methods Of the 60 SD rats,15 were randomly selected as sham operation group(only underwent T9~T10 laminectomy),and the remaining 45 rats were used to establish the acute spinal cord injury model using the modified Allens technique.After the successful establishment of spinal cord injury model,the rats were randomly divided into model group,liraglutide group and liraglutide+XAV939 group,with 15 rats in each group.During the first 14 days after spinal cord injury,the rats in the sham operation group and model group were subcutaneously injected with 50 mg/kg of saline daily,while the rats in the liraglutide group were subcutaneously injected with 50μg/kg of liraglutide daily.The rats in the liraglutide+XAV939 group were subcutaneously injected with 50μg/kg of liraglutide and 0.4 mg/kg of XAV939(a small molecule inhibitor of the Wnt/β-catenin signaling pathway)daily.Lower limb motor function of rats were assessed by BBB scoreing method before surgery,intervention 7th day and 14th day.On the 14th day,the protein expression levels ofβ-catenin,caspase-3,tumor necrosis factorα(TNF-α)and interleukin 6(IL-6)were analyzed by Western blot and immunohistochemistry.On the 14th day,the neural cell changes in rat spinal cord tissue were observed by HE and Nissl staining.Results There was no difference in BBB scores between the groups before operation.After intervention 7 d and 14 d,BBB scores in the model group,liraglutide and liraglutide+XAV939 group were significantly lower than the sham group(P<0.05),and the BBB score was significantly higher in liraglutide group than model group and liraglutide+XAV939 group(P<0.05),while the difference in the model group and liraglutide+XAV939 group was not statistically significant(P>0.05).The number of positive cells in the spinal cord in the model group,liraglutide group and liraglutide+XAV939 group was significantly low
作者
崔拥国
杨成亮
李晓强
李奕廷
黄昊
刘佳
CUI Yongguo;YANG Chengliang;LI Xiaoqiang;LI Yiting;HUANG Hao;LIU Jia(Youjiang Medical College for Nationalities,Guangxi Zhuang Autonomous Region;Affiliated Hospital of Youjiang Medical College for Nationalities,Baise Guangxi 533000,China)
出处
《新疆医科大学学报》
CAS
2024年第4期500-505,共6页
Journal of Xinjiang Medical University
基金
国家自然科学基金项目(82071361)。
