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目的研究胰岛素样生长因子-1(IGF-1)经鼻靶向中枢给药对缺氧缺血性脑损伤(HIBD)新生大鼠内源性神经干细胞(NSCs)的保护性治疗作用。方法取90只7日龄SD新生大鼠随机分为假手术组、模型对照组、IGF-1干预组。采用Rice法制作新生大鼠HIBD动物模型。模型对照组于缺氧缺血后1 h鼻腔递送9 g·L-1盐水0.1 mL;IGF-1干预组于缺氧缺血后1 h鼻腔递送IGF-1 2.5μg(溶于9 g·L-1盐水0.1 mL);假手术组仅分离颈总动脉,不结扎不行缺氧处理。术后1、3、5、7、14 d取其脑组织,采用单、双标免疫组织化学方法检测其侧脑室室管膜下区(SVZ)BrdU阳性细胞和巢蛋白(Nestin)阳性细胞、双阳性细胞的表达;并计算BrdU阳性细胞数、Nestin阳性细胞数及BrdU-Nestin双阳性细胞数;HE染色观察其脑损伤组织形态结构变化。结果模型对照组:术后1 d SVZ区BrdU、Nestin、BrdU-Nestin阳性细胞开始增加,第3天达高峰,术后7 d明显减少,术后14 d SVZ仅有少量细胞;IGF-1干预组:术后1 d SVZ 3种阳性细胞明显增多,术后3 d增加急剧,术后5 d达高峰,术后7 d开始减少,术后14 d减少明显,每个时间点IGF-1干预组均高于模型对照组(Pa<0.05);假手术组无明显增殖现象,与其他2组比较差异有统计学意义(P<0.05)。结论经鼻腔导入IGF-1对HIBD大鼠内源性NSCs具有明显的保护作用。
Objective To investigate the protective effect of insulin-like growth factor-1 (IGF-1) administered to the central nervous system (NSCs) of neonatal rats with hypoxic-ischemic brain damage (HIBD) through nasal targeting. Methods Ninety SD neonatal rats of 7 days old were randomly divided into sham operation group, model control group and IGF-1 intervention group. Newborn rat HIBD animal model was made by the method of Rice. The model control group delivered 0.1 mL of 9 g · L-1 saline 1 h after hypoxia-ischemia; IGF-1 2.5 μg (n = 9) dissolved in 9 g · L -1 saline 0.1 mL). Only the common carotid artery was separated in the sham operation group, and no hypoxia treatment was not performed without ligation. The brains were taken at 1, 3, 5, 7, and 14 days after operation. BrdU positive cells and nestin positive cells in the subventricular zone (SVZ) of the lateral ventricle were detected by single and double immunohistochemistry. Double positive cells. The number of BrdU positive cells, the number of Nestin positive cells and the number of BrdU-Nestin double positive cells were calculated. The morphological changes of brain tissue were observed by HE staining. Results In the model control group, BrdU, Nestin and BrdU-Nestin positive cells in SVZ began to increase on the 1st postoperative day, reached a peak on the 3rd day and decreased significantly on the 7th postoperative day, with only a small amount of SVZ on the 14th postoperative day. IGF-1 intervention Group: The number of SVZ positive cells increased significantly on the 1st postoperative day, increased sharply on the 3rd postoperative day, reached the peak on the 5th postoperative day, decreased on the 7th postoperative day, and decreased significantly on the 14th postoperative day. At each time point, IGF-1 intervention (P <0.05). There was no significant proliferation in the sham operation group, which was significantly different from the other two groups (P <0.05). Conclusion Intranasal administration of IGF-1 has a significant protective effect on endogenous NSCs in HIBD rats.