缺氧预处理对大鼠颅脑损伤后海马神经元和行为学的影响

Effects of hypoxic preconditioning on hippocampal neurons and behavioristics in rats after traumatic brain injury

目的探讨缺氧预处理对创伤性颅脑损伤大鼠海马神经元活性的影响及其机制。方法将72只SD大鼠,随机分为对照组(n=6)、缺氧预处理组(HPC组,n=6)、创伤性颅脑损伤组(TBI组,n=30)、缺氧预处理+创伤性颅脑损伤组(HPCT组,n=30)。采用改良Freeny’s法制作TBI模型,在低压氧舱内对大鼠进行缺氧预处理。伤后3 h、12 h、1 d、7 d、14 d,对四组大鼠进行神经功能评分(NSS),采用免疫组化染色检测海马CA1区基质金属蛋白酶-9(MMP-9)和神经元核抗原(NeuN)的表达水平。结果与对照组比较,TBI组伤后3 h^7 d MMP-9表达增加,3 h^14 d NSS评分增加而NeuN表达减少,差异有统计学意义(P<0.05);HPCT组12 h^7 d MMP-9表达增加,3 h^14 d NSS评分增加,12 h^14 d NeuN表达减少(P<0.05)。与TBI组比较,HPCT组3 h^7 d MMP-9表达明显减少而NeuN表达明显增加,12 h^7 d NSS评分明显减少(P<0.05)。结论缺氧预处理能减少TBI后海马区MMP-9的表达,减轻海马神经元的损伤程度。

Objective To explore th e effect of hypoxic preconditioning on hippocampal neuron activity in rats after traumatic brain injury and its mechanisms. Methods Seventy-two SD rats were randomly divided into control group（n = 6）, hypoxic preconditioning group（HPC, n = 6）, traumatic brain injury group（TBI, n = 30） and traumatic brain injury after hypoxic preconditioning group（HPCT,n = 30）. TBI model was established by modified Freeny＇s method. The rats were put in hypobaric chamber for hypoxic preconditioning.The neurological functions of rats in 4 groups were evaluated by the Neurological Severity Score（NSS） and the expression of matrix metallproteinase-9（MMP-9） and Neu N in hippocampus CA1 were observed by immunohistochemical staining 3, 12 h and 1, 7, 14 d after injury. Results Compared with control group, the expression of MMP-9 from 3 h to 7 d after injury in the TBI group was significantly increased, the NSS from 3 h to 14 d after injury was increased and the expression of Neu N was significantly decreased（P〈0.05）. Compared with control group, the expression of MMP-9 from 12 h to 7 d after injury in the HPCT group was significantly increased, the NSS from 3 h to 14 d after injury was increased and the expression of Neu N from 12 h to 14 d was significantly decreased（P〈0.05）. Compared with TBI group, the expression of MMP-9 from 3 h to 7 d and the NSS from 12 h to 7 d was significantly decreased, while the expression of Neu N from 3 h to 7 d was increased significantly（P〈0.05）. Conclusions Hypoxic preconditioning can ameliorate the lesions of hippocampal neurons after TBI by reducing the expression of MMP-9 in the hippocampal region.