摘要
目的 探索透明质酸-半乳糖化壳聚糖复合支架（HGC）联合牛磺酸（Tau）对脑创伤（TBI）大鼠的治疗作用.方法 选择成年SD大鼠40只,随机分为假手术组（Sham组）、脑创伤组（TBI组）、透明质酸-半乳糖化壳聚糖复合支架组（HGC组）、透明质酸-半乳糖化壳聚糖复合支架与牛磺酸联合治疗组（HGC-Tau组）,每组10只.TBI、HGC及HGC-Tau组采用液压打击法在大鼠左侧大脑半球制作TBI模型,Sham组仅在相同位置开骨窗,不予打击.HGC组于造模后7d将30μl HGC植入大鼠脑皮质损伤区,HGC-Tau组以同样方法植入相同体积HGC与牛磺酸的混合物.TBI后1、3、7、10、14、21 d进行改良型神经功能评分（mNSS）,其中17～21 d进行Morris水迷宫（MWM）实验.TBI后28 d采用实时定量PCR及免疫荧光染色检测胶质纤维酸性蛋白质（GFAP）的基因及蛋白表达水平.结果 HGC-Tau组mNSS评分在TBI后14d及21d显著低于TBI组（P＜0.05）,HGC组各时间点评分与TBI组相比,差异均无统计学意义（P＞0.05）,HGC-Tau组与HGC组相比,评分在TBI后14、21 d显著降低（P＜0.05）;HGC-Tau组MWM检测目标象限百分比从创伤后18d开始明显大于TBI组（P＜0.05）,HGC组创伤后21 d目标象限百分比显著大于TBI组（P＜0.05）,HGC-Tau组仅在18、19 d目标象限百分比明显大于HGC组（P＜0.05）;HGC组及HGC-Tau组TBI后28 dGFAP mRNA及蛋白表达量与TBI组相比显著下降（P＜0.05）,且较HGC组,HGC-Tau组下降更加明显（P＜0.05）.结论 单纯使用HGC仅能抑制创伤性脑损伤后胶质细胞增生,对神经功能改善无明显作用.HGC联合Tau治疗可抑制重型脑损伤后胶质细胞增生,改善神经功能,表明生物材料与药物联合治疗脑外伤具有一定的应用前景.
Objective To investigate the treatment effect of hyaluronic acid-galactosylated chitosan scaffold （HGC） combined with taurine （Tau） in traumatic brain injury （TBI） after implanted to the injured cortex in rat.Methods Forty SD rats were equally divided into Sham group,TBI group,HGC treated group （HGC group） and HGC plus taurine treated group （HGC-Tau group）.Rats in TBI,HGC and HGC-Tau group were subjected to severe traumatic injury of left brain by lateral fluid percussion device,while sham control rats underwent the same surgical procedure weren＇t exposed to percussion injury.Rats in HGC group were implanted with 30 μl HGC at brain cortical lesion site 7 d after TBI immediately.HGC-Tau group rats were implanted with HGC and taurine with same volume at the same site post-TBI at the same time.Modified neurological severity score （mNSS） test was conducted at 1,3,7,10,14 and 21 d after TBI.Morris water maze （MWM） was used to detect the spatial reference memory for 5 consecutive days starting on 17 d after TBI.RT-PCR and immunohistochemistry for glial fibrillary acidic protein （GFAP） were performed at 28 d after TBI.Results The HGC-Tau treated group had significantly improved functional outcome at 14 and 21 d after TBI measured by mNSS test,compared with both TBI group and HGC group （P〈0.05）,While there was no significant difference between HGC group and TBI group in mNSS test at all time points （P〉0.05）.HGC-Tau treatment could improve spatial learning ability of rats at all time points except 17 d after TBI in MWM test （P〈0.05）.The mean ratios of time spent in the target quadrant were significantly higher in the HGC-Tau treated group when compared to the TBI control group at 21 d （P〈0.05）.The mean percentages of rats in HGC-Tau treated group were significantly higher than that of the HGC group at 18 and 19 d after TBI （P〈0.05）.RTPCR showed that the rats in both HGC-Tau group and HGC group have lower expression of GFAP mRNA compared to the rats in TBI group （P〈0.05）.GFAP mRNA expression in HGC-Tau group was higher than that in HGC group （P〈0.05）.Immuocytochemical fluorescent staining showed the same tendency.Conclusions Pure HGC can only inhibit reactive astrocytes post-TBI,while HGC combined with taurine can inhibit reactive astrocytes and promote the recovery of neural function in rats with severe TBI.Biomaterials combined with drug have a certain application prospect.
出处
《国际生物医学工程杂志》
CAS
2014年第2期65-70,I0001,共7页
International Journal of Biomedical Engineering
基金
国家973计划资助项目（2011CB606202）
关键词
壳聚糖
半乳糖
透明质酸
牛磺酸
脑损伤
Chitosan
Galactose
Hyaluronic acid
Taurine
Traumatic brain injury
