阿托伐他汀对颅脑损伤大鼠神经元凋亡的抑制作用  

Inhibitive effect of atorvastatin on neuron apoptosis in rats with traumatic brain injury and its mechanism

作　　者：唐菁华[1] 孙秀勤[1] 王建军[1] TANG Jing-hua;SUN Xiu-qin;WANG Jian-jun(Department of Pediatrics,Affiliated Hospital,North Sichuan Medical College,Nanchong 637000,China)

机构地区：[1]川北医学院附属医院儿科,四川南充637000

出　　处：《中国临床神经外科杂志》2020年第4期227-230,共4页Chinese Journal of Clinical Neurosurgery

摘　　要：目的探讨阿托伐他汀对颅脑损伤(TBI)大鼠神经元凋亡的抑制作用及机制。方法30只SD大鼠随机分为假手术组、模型组和阿托伐汀他组,各10只。采用液压打击法制作TBI模型,阿托伐他汀组连续灌胃阿托伐他汀2周(1 mg/kg/d),假手术组、模型组灌胃等体积生理盐水。给药结束后第2天,参照Zea Longa 5分制标准进行神经功能评分。酶联免疫吸附法检测血清肿瘤坏死因子(TNF-α)、白介素(IL)-6和IL-1β水平;免疫印迹法检测损伤脑组织Toll样受体4(TLR4)、核转录因子(NF)-κB p65、p-IκB、cleaved Caspase-3蛋白表达;末端标记法检测神经元凋亡;HE染色观察脑组织病理变化。结果与模型组相比,阿托伐他汀组大鼠神经功能缺损评分、细胞凋亡率、血清IL-6、TNF-α和IL-1β水平明显改善(P<0.05),损伤脑组织TLR4、NF-KB p65、p-IκB、cleaved Caspase-3水平明显下调(P<0.05);HE染色显示脑组织损伤程度明显减轻。结论阿托伐他汀可能通过抑制TLR4/NF-кB信号通路,抑制TBI大鼠的神经元细胞凋亡,促进神经功能恢复。Objective To analyze inhibitive effect of atorvastatin on neuron apoptosis in the rats with traumatic brain injury(TBI)and its mechanism.Methods Thirty SD rats were randomly divided into 3 groups of 10 animals each,i.e.sham operation group,model group and atorvastatin group.TBI models were made by fluid-percussion technique.The oral administration of atorvastatin(1 mg/kg/d)was performed for 2 weeks in the rats of atorvastatin group after the successful establishment of TBI model.The neurological function defects were determined by Zea Longa method after the treatment.The serum levels of tumor necrosis factor(TNF-α),interleukin(IL)-6 and IL-1β were detected by enzyme linked immunosorbent assay.The expressions of Toll-like receptor 4 gene(TLR4),nuclear factor(NF)-κB p65,p-IκB and cleaved Caspase-3 protein in the injured brain tissues were determined.The apoptosis of the neurons in the injured brain tissues was determined by TdT-mediated dUTP nick end labeling and the pathological change in the injured brain tissues was observed by HE staining.Results The scores of neurological function defects,apoptosis rate of the neurons,the levels of serum IL-6,TNF-α and IL-1β and the levels of TLR4,NF-κB p65,p-IκB and cleaved Caspase-3 protein expressions in the injured brain tissues were significantly lower in atorvastatin group than those in the model group(P<0.05).HE staining showed that the degree of damage to the brain tissues was obviously reduced in atorvastatin group compared to that in the model group.Conclusion Atorvastatin may inhibit apoptosis of neurons by inhibiting TLR4/NF-кB signaling pathway in the rats with TBI.

关 键 词：颅脑损伤 阿托伐他汀 大鼠 神经元 细胞凋亡 

分 类 号：R651.15[医药卫生—外科学] Q786[医药卫生—临床医学]