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目的探寻弥漫性脑损伤后基质金属蛋白酶(MMP)表达的动态变化及其与细胞凋亡的关系。方法84只大鼠随机分为3组:空白组(不做脑室注射)、盐水组(脑室注射生理盐水)和实验组(脑室注射抑制剂),分别在伤后30 min、1、3、6 h、1、3和7 d处死大鼠,断头取脑。用TUNEL法检测细胞凋亡,明胶酶谱法检测MMP表达。结果酶原型MMP-9在伤后30 min就有表达,1 d时达到峰值,而后下降,7 d后未回落到伤后30 min水平;酶原型MMP-2,呈双峰形式,30 min就有表达,6 h到达第1个高峰,然后下降,3 d时再次升高到达第2个峰值,7 d后小幅回落;活性型MMP-2的表达呈逐渐上升形式,30 min就有表达,7 d时达到高峰。MMP抑制剂对各种MMP表达的作用各不相同,它可上调酶原型MMP-9的表达(P<0.01),下调活性型MMP-2的表达(P<0.01),对酶原型MMP-2的表达无影响。MMP抑制剂在各个时间点上,均可减少细胞凋亡(P<0.01)。结论弥漫性脑损伤后,不同的MMP有不同的表达形式:酶原型MMP-9呈单峰型,酶原型MMP-2呈双峰型,活性型MMP-2呈上升型。MMP抑制剂能上调酶原型MMP-9的表达,抑制活性型MMP-2的表达,可降低细胞凋亡,具有一定的神经保护作用。
Objective To investigate the dynamic changes of matrix metalloproteinase (MMP) expression and its relationship with apoptosis after diffuse brain injury. Methods Eighty - four rats were randomly divided into three groups: blank group (without intraventricular injection), saline group (intraventricular injection of normal saline) and experimental group (intraventricular injection inhibitor) Rats were sacrificed on days 1, 3, and 7, and their brains were decapitated. Apoptosis was detected by TUNEL method and MMP expression was detected by gelatin zymography. Results MMP-9 was detected at 30 min after injury and peaked on the 1st day, then decreased and did not drop back to 30 min after 7 d. Enzyme-like MMP-2 showed a bimodal pattern at 30 min Expression reached the first peak at 6 h, then decreased and reached the second peak again on the third day, then decreased slightly after 7 d. The expression of active MMP-2 was gradually increased and expressed at 30 min, 7 d peak. MMP inhibitors could upregulate the expression of MMP-9 (P <0.01) and down-regulate the expression of active MMP-2 (P <0.01) No effect on expression. MMP inhibitors decreased apoptosis at all time points (P <0.01). Conclusions After diffuse brain injury, the expression of different MMPs is different: MMP-9 is a unimodal type, enzymatic type MMP-2 is bimodal type, and active MMP-2 is an ascending type. MMP inhibitors can upregulate the expression of the proenzyme MMP-9 and inhibit the expression of active MMP-2, which can reduce apoptosis and have certain neuroprotective effects.