经鼻给予肝素结合表皮生长因子样生长因子对脑出血大鼠血肿周围组织巢蛋白和胱天蛋白酶-3表达的影响  

Effects of intranasal administration of heparin-binding epidermal growth factor-like growth factor on expressions of nestin and caspase-3 in the perihematomal tissue after intracerebral hemorrhage in rats

作　　者：范子豫[1] 郭辉[1] 赛音巴雅尔[1] 林贵军[1] 

机构地区：[1]北京大学航天临床医学院神经外科,100049

出　　处：《国际脑血管病杂志》2016年第3期219-224,共6页International Journal of Cerebrovascular Diseases

摘　　要：目的：探讨经鼻腔给予肝素结合表皮生长因子样生长因子（heparin binding epidermal growth factor-like growth factor, HB-EGF）对脑出血大鼠血肿周围组织巢蛋白和胱天蛋白酶-3表达水平的影响。方法36只成年雄性 Sprague-Dawley 大鼠随机分为 HB-EGF 组、对照组和假手术组（各12只）,然后进一步分为4 d、7 d和10 d亚组（每亚组各4只）。采用Ⅳ型胶原酶注射法制作脑出血模型。 HB-EGF组在模型制作后1~3 d经鼻腔给予 HB-EGF,对照组给予等体积生理盐水。在相应时间点进行Bederson评分和前肢放置实验后处死大鼠,采用免疫组化法检测血肿周围组织巢蛋白和胱天蛋白酶-3表达。结果假手术组无神经功能缺损,HB-EGF 组在4 d和7 d时 Bederson 评分（P 均〈0．05）和前肢放置实验结果（P 均〈0．01）均显著优于对照组,但10 d时不再有统计学差异。在4 d、7 d和10 d时,HB-EGF组血肿周围组织巢蛋白阳性细胞数量均显著多于对照组（P 均〈0．05）,而胱天蛋白酶-3阳性细胞数量均显著少于对照组（P 均〈0．01）。结论经鼻腔给予 HB-EGF 可改善脑出血大鼠早期神经功能,上调血肿周围组织巢蛋白表达和下调胱天蛋白酶-3表达,提示经鼻腔给予 HB-EGF可促进血肿周围组织神经前体细胞增殖并减轻细胞凋亡。Objective To investigate the effects of intranasal administration of heparin-binding epidermal growth factor-like growth factor （HB-EGF） on expressions of nestin and caspase-3 in the perihematomal tissue after intracerebral hemorrhage in rats. Methods A total 36 adult male Sprague-Dawley rats were randomly divided into 3 groups： an HB-EGF group, a control group, and a sham operation group （n = 12 in each group）. Then they were further divided into 4-, 7-, and 10-day subgroups （n = 4 in each subgroup）. A model of intracerebral hemorrhage was induced by injecting type Ⅳ colagenase. At 1 to 3 days after modeling, the HB-EGF group was intranasaly administrated HB-EGF. The control group was administrated the same volume of saline. The Bederson score was conducted at the corresponding time points and the rats were sacrificed after the forelimb placing test. Immunohistochemistry was used to detect the expression of nestin and caspase-3 in the perihematomal tissue. Results The sham operation group did not have neurological deficits. The Bederson scores （P 〈 0. 05） and the result of forelimb placing test （al P 〈 0. 01） at day 4 and 7 in the HB-EGFgroup were better than those in the control group. There were no significant differences at day 10. At day 4, 7, and 10, the number of nestin positive cels in the perihematomal tissue in the HB-EGF group was significantly more than that in the control group （al P 〈 0. 05）, and the number of caspase-3 positive cels was less than that in the control group （al P 〈 0. 01）. Conclusions Intranasal administration of＆amp;nbsp;HB-EGF can improve the early neurological function, upreguate the nestin expression and downregulate the caspase-3 expression in the perihematomal tissue after intracerebral hemorrhage in rats, indicating that intranasal administration of HB-EGF may promote the proliferation of precursor cels and decrease cel apoptosis in the perihematomal tissue.

关 键 词：脑出血 肝素结合表皮生长因子样生长因子 神经元 巢蛋白 胱天蛋白酶 3 神经保护药 疾病模型 动物 大鼠 

分 类 号：R743.34[医药卫生—神经病学与精神病学]