齐墩果酸调节SDF-1/CXCR4信号通路对创伤性脑损伤大鼠神经元凋亡的影响  

Effects of oleanolic acid on neuronal apoptosis in rats with traumatic brain injury by regulating SDF-1/CXCR4 signaling pathway

作　　者：龚杨[1] 朱小芳[1] 陈亚玲[1] 陈芬 GONG Yang;ZHU Xiao-Fang;CHEN Ya-Ling(Jingzhou Central Hospital,Jingzhou 434020,Hubei,China)

机构地区：[1]荆州市中心医院,湖北荆州434020 [2]华中科技大学同济医学院附属协和医院心内科 [3]华中科技大学生物靶向治疗研究湖北省重点实验室 [4]华中科技大学心血管疾病免疫诊疗湖北省工程研究中心

出　　处：《中国老年学杂志》2024年第18期4442-4447,共6页Chinese Journal of Gerontology

基　　金：国家自然科学基金项目(No.81300196)。

摘　　要：目的探讨齐墩果酸调节基质细胞衍生因子(SDF)-1/CXC型趋化因子受体(CXCR)4信号通路对创伤性脑损伤(TBI)大鼠神经元凋亡的影响。方法取SD大鼠以改良Feeney自由落体打击法构建TBI大鼠模型,随机分为模型组、齐墩果酸低、高剂量(25、50 mg/kg)组、齐墩果酸高剂量(50 mg/kg)+AMD3100(SDF-1/CXCR4信号拮抗剂,5μg/kg)组,每组12只,另取12只SD大鼠设为假手术组,采用齐墩果酸和AMD3100处理后,采用改良神经功能缺损评分(mNSS)和避暗实验评测大鼠神经功能损伤;检测脑含水量来评测大鼠脑水肿;采用TUNEL染色检测各组脑皮质与海马神经元凋亡;采用酶联免疫吸附测定(ELISA)试剂盒检测血清及脑组织促炎因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β水平;采用免疫印迹检测脑组织凋亡[cleaved胱天蛋白酶(caspase)-3、B细胞淋巴瘤(Bcl)-2相关X蛋白(Bax)、Bcl-2]、SDF-1/CXCR4通路相关蛋白表达。结果与假手术组比较,模型组mNSS评分、犯错次数、脑含水量、脑皮质与海马神经元凋亡比例、脑组织与血清TNF-α、IL-1β水平、脑组织cleaved caspase-3及Bax蛋白表达显著升高,步入潜伏期、脑组织Bcl-2、SDF-1及CXCR4蛋白表达显著降低(P<0.05)。与模型组比较,齐墩果酸低、高剂量组mNSS评分、犯错次数、脑含水量、脑皮质与海马神经元凋亡比例、脑组织与血清TNF-α、IL-1β水平、脑组织cleaved caspase-3及Bax蛋白表达显著降低,步入潜伏期、脑组织Bcl-2、SDF-1及CXCR4蛋白表达显著升高(P<0.05);齐墩果酸高剂量组mNSS评分、犯错次数、脑含水量、脑皮质与海马神经元凋亡比例、脑组织与血清TNF-α、IL-1β水平、脑组织cleaved caspase-3及Bax蛋白表达相比齐墩果酸低剂量组显著降低,步入潜伏期、脑组织Bcl-2、SDF-1及CXCR4蛋白表达显著升高(P<0.05)。与齐墩果酸高剂量组比较,齐墩果酸高剂量+AMD3100组mNSS评分、犯错次数、脑含水量、脑皮质与海马�Objective To investigate the impacts of oleanolic acid on apoptosis of neurons in rats with traumatic brain injury(TBI)by regulating stromal cell-derived factor(SDF)-1/CXC chemokine receptor(CXCR)4 signaling pathway.Methods SD rats were selected to construct TBI rat model by modified Feeney free fall hit method.Rats were randomly divided into model group,low and high dose oleanolic acid(25,50 mg/kg)groups,high dose oleanolic acid(50 mg/kg)+AMD3100(SDF-1/CXCR4 signal antagonist,5μg/kg)group,with 12 rats in each group,and an additional 12 SD rats were regarded as the sham surgery group,after treatment with oleanolic acid and AMD3100,modified neurological severity score(mNSS)and dark avoidance experiment were used to evaluate neural function damage in rats;the detection of brain water content was applied to evaluate brain edema in rats;the neuronal apoptosis in the cerebral cortex and hippocampus in each group were detectd by TUNEL staining;enzyme-linked immunosorbent assay(ELISA)kit was applied to detect the levels of pro-inflammatory factors such as tumor necrosis factor(TNF)-αand interleukin(IL)-1βlevels in serum and brain tissue;immunoblotting was used to detect brain apoptosis〔cleaved caspase-3,B-cell lymphoma(Bcl)-2-associated X protein(Bax),Bcl-2〕and the expressions of SDF-1/CXCR4 pathway related protein in brain tissue.Results Compared with the sham surgery group,the mNSS score,number of mistakes made,brain water content,proportion of apoptosis in cortical and hippocampal neurons,levels of TNF-αand IL-1βin brain tissue and serum,and expressions of cleaved caspase-3 and Bax protein in brain tissue in the model group were significantly increased,the step through latency,the expressions of Bcl-2,SDF-1,and CXCR4 protein in brain tissue were significantly decreased(P<0.05).Compared with the model group,the mNSS score,number of mistakes made,brain water content,proportion of apoptosis in cortical and hippocampal neurons,levels of TNF-αand IL-1βin brain tissue and serum,and expressions of cleaved caspase

关 键 词：齐墩果酸 基质细胞衍生因子(SDF)-1/CXC型趋化因子受体(CXCR)4 创伤性脑损伤 神经元凋亡 

分 类 号：R743.3[医药卫生—神经病学与精神病学]