中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (30): 7893-7901.doi: 10.12307/2026.932

• 神经组织构建 nerve tissue construction • 上一篇    下一篇

碱性成纤维细胞生长因子-壳聚糖凝胶减轻脑出血后的脑损伤

许玲瑞,郝  鹏,段红梅,赵  文,高钰丹,马新月,李晓光,杨朝阳   

  1. 首都医科大学基础医学院,北京市  100069

  • 收稿日期:2026-03-13 修回日期:2026-06-02 出版日期:2026-10-28 发布日期:2026-09-12
  • 通讯作者: 杨朝阳,博士,教授,首都医科大学基础医学院,北京市 100069 通讯作者:李晓光,博士,教授,首都医科大学基础医学院,北京市 100069
  • 作者简介:许玲瑞,女,2001年生,河北省唐山市人,汉族,硕士,主要从事生物活性材料治疗中枢神经系统疾病研究。

Basic fibroblast growth factor-chitosan alleviates brain injury after cerebral hemorrhage

Xu Lingrui, Hao Peng, Duan Hongmei, Zhao Wen, Gao Yudan, Ma Xinyue, Li Xiaoguang, Yang Zhaoyang   

  1. School of Basic Medicine, Capital Medical University, Beijing 100069, China
  • Received:2026-03-13 Revised:2026-06-02 Online:2026-10-28 Published:2026-09-12
  • Contact: Yang Zhaoyang, PhD, Professor, School of Basic Medicine, Capital Medical University, Beijing 100069, China Co-corresponding author: Li Xiaoguang, PhD, Professor, School of Basic Medicine, Capital Medical University, Beijing 100069, China
  • About author:Xu Lingrui, MS, School of Basic Medicine, Capital Medical University, Beijing 100069, China

摘要:



文题释义:
脑出血后脑损伤:分为原发性损伤与继发性损伤,原发性损伤是指血肿直接压迫引起的机械损伤,继发性损伤是指由血肿内容物释放引发的一系列病理生理反应,包括轴突脱髓鞘、神经元变性、细胞凋亡等过程,导致神经功能缺损。
碱性成纤维细胞生长因子-壳聚糖:碱性成纤维细胞生长因子是一种在中枢神经系统中广泛存在的神经营养因子,具有稳定性差、半衰期短的特点。由壳聚糖负载碱性成纤维细胞生长因子制成具有缓释效果的凝胶材料,能够在损伤部位持续释放碱性成纤维细胞生长因子。

背景:研究证实,碱性成纤维细胞生长因子-壳聚糖凝胶可促进脑卒中腔内的神经元新生和血管再生、重建功能性神经环路、改善神经功能,但这种生物活性材料对出血性脑卒中的作用尚不清楚。
目的:观察碱性成纤维细胞生长因子-壳聚糖凝胶对大鼠脑出血后血肿吸收、神经元凋亡、髓鞘保护及运动神经功能恢复的干预效果。
方法:构建碱性成纤维细胞生长因子-壳聚糖凝胶。将122只雄性Wistar大鼠随机分3组,模型组(n=50)与治疗组(n=38)将大鼠自体尾动脉血注射至右侧纹状体建立脑出血模型,假手术组(n=34)不建模;术后3 h,治疗组右侧纹状体注射碱性成纤维细胞生长因子-壳聚糖凝胶,模型组右侧纹状体注射生理盐水。术后1,3,7 d,检测全脑组织血肿体积;术后3 d,取右侧脑组织损伤部位分别进行TUNEL染色与髓鞘碱性蛋白免疫荧光染色,检测细胞凋亡与轴突脱髓鞘情况;术后7 d,检测脑水肿含量,取右侧脑组织损伤部位分别进行苏木精-伊红染色、尼氏染色与神经元核抗原免疫荧光染色,检测血肿吸收与神经元损伤情况;术后14 d,取右侧脑组织损伤部位分别进行透射电子显微镜观察与髓鞘碱性蛋白免疫荧光染色,检测髓鞘超微结构与髓鞘再生情况;术后1,3,7,14 d,称大鼠体质量,通过圆筒实验、改良神经功能缺损(mNSS)评分检测大鼠运动功能恢复情况。
结果与结论:①治疗组术后1,3 d的脑血肿体积小于模型组,术后7 d的脑含水量低于模型组;苏木精-伊红染色显示,治疗组大鼠脑血肿吸收情况优于模型组;TUNEL染色显示,治疗组细胞凋亡比例低于模型组;尼氏染色与神经元核抗原免疫荧光染色显示,治疗组神经元损伤情况轻于模型组;透射电子显微镜观察与髓鞘碱性蛋白免疫荧光染色显示,治疗组大鼠脑出血后急性脱髓鞘情况轻于模型组,脑出血后慢性期的髓鞘再生情况优于模型组;术后14 d,治疗组大鼠体质量高于模型组;圆筒实验、mNSS评分显示,治疗组大鼠运动功能恢复情况优于模型组。②结果表明,碱性成纤维细胞生长因子‑壳聚糖凝胶通过促进血肿吸收、抑制细胞凋亡、保护髓鞘多靶点发挥神经保护作用,促进脑出血后大鼠运动神经功能的恢复。
https://orcid.org/0009-0008-8949-9878(许玲瑞)


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 脑出血, 脑损伤, 碱性成纤维细胞生长因子-壳聚糖, 凋亡, 血肿消退, 髓鞘保护, 运动神经功能

Abstract: BACKGROUND: Studies have shown that basic fibroblast growth factor-chitosan gels can promote neuronal neurogenesis and vascular regeneration within the stroke lesion, restore functional neural circuits, and improve neurological function; however, the effects of this bioactive material on hemorrhagic stroke remain unclear.
OBJECTIVE: To observe the intervention effects of basic fibroblast growth factor-chitosan gels on hematoma absorption, neuronal apoptosis, myelin protection, and motor neurological function recovery after intracerebral hemorrhage in rats.
METHODS: Basic fibroblast growth factor-chitosan gel was prepared. A total of 122 male Wistar rats were randomly divided into three groups: model group (n=50) and treatment group (n=38) received autologous tail arterial blood injected into the right striatum to establish an intracerebral hemorrhage model, while the sham operation group (n=34) did not undergo modeling. Three hours after surgery, the treatment group received an injection of basic fibroblast growth factor-chitosan gel into the right striatum, and the model group received an injection of normal saline into the right striatum. At 1, 3, and 7 days after surgery, the hematoma volume in the whole brain tissue was measured. At 3 days after surgery, the injured area of the right brain tissue was collected for TUNEL staining and myelin basic protein immunofluorescence staining to detect apoptosis and axonal demyelination. At 7 days after surgery, brain edema content was measured, and the injured area of the right brain tissue was collected for hematoxylin-eosin staining, Nissl staining, and neuronal nuclear antigen immunofluorescence staining to detect hematoma absorption and neuronal injury. At 14 days after surgery, the injured area of the right brain tissue was collected for transmission electron microscopy observation and myelin basic protein immunofluorescence staining to detect myelin ultrastructure and remyelination. At 1, 3, 7, and 14 days after surgery, rat body mass was measured, and motor function recovery was assessed using the cylinder test and modified Neurological Severity Score.
RESULTS AND CONCLUSION: The hematoma volume in the treatment group was smaller than that in the model group at 1 and 3 days after surgery, and brain water content was lower than that in the model group at 7 days after surgery. Hematoxylin-eosin staining showed that hematoma absorption in the treatment group was better than that in the model group. TUNEL staining showed that the proportion of apoptotic cells in the treatment group was lower than that in the model group. Nissl staining and neuronal nuclear antigen immunofluorescence staining showed that neuronal injury in the treatment group was milder than that in the model group. Transmission electron microscopy observation and myelin basic protein immunofluorescence staining showed that acute demyelination after intracerebral hemorrhage in the treatment group was milder than that in the model group, and remyelination in the chronic phase after intracerebral hemorrhage was better than that in the model group. At 14 days after surgery, the body mass of rats in the treatment group was higher than that in the model group. The cylinder test and modified Neurological Severity Score showed that motor function recovery in the treatment group was better than that in the model group. Overall, these findings indicate that basic fibroblast growth factor-chitosan gels exert neuroprotective effects by promoting hematoma absorption, inhibiting apoptosis, and protecting myelin through multiple targets, thereby facilitating motor neurological function recovery in rats after intracerebral hemorrhage.


Key words: intracerebral hemorrhage, brain injury, basic fibroblast growth factor-chitosan, apoptosis, hematoma resolution, myelin protection, motor functional recovery

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