摘要
目的观察连续性侧脑室注入基质细胞衍生因子-1α(stromal cell-derived factor-1 alpha,SDF-1α)对大鼠脑梗死后远离梗死灶的同侧丘脑细胞增殖和血管再生的影响,并探讨其可能的机制。方法将36只脑梗死大鼠随机分为SDF-1α治疗组、溶剂对照组和SDF-1α+CXCR4拮抗剂组,每组12只。所有大鼠分别于右侧大脑中动脉皮层支闭塞(middle cerebral artery occlusion,MCAO)术后第7 d和14 d处死,处死前经腹腔注射5-溴脱氧尿嘧啶核苷(5-bromo-2-deoxyuridine,BrdU)以标记新增殖的细胞,通过苏木素-伊红染色计算脑梗死体积,采用免疫荧光染色法检测梗死侧丘脑腹后外侧核(ventroposterior nucleus,VPN)内BrdU+细胞数目、血管密度及BrdU+/laminin+细胞数目。结果与溶剂对照组及SDF-1α+CXCR4拮抗剂组相比,SDF-1α治疗组大鼠的脑梗死体积减少(术后7 d:12.3%±0.68%vs.20.6%±1.02%vs.17.2%±0.84%、术后14 d:10.4%±0.90%vs.17.8%±0.77%vs.15.0%±0.86%,P<0.05);梗死侧丘脑VPN内BrdU+细胞表达增加(术后7 d:132.7±9.11 vs.90.5±9.35 vs.96.83±8.01,术后14 d:264.2±11.65 vs.192.2±6.18 vs.207.3±7.53,P<0.05),同时BrdU+/laminin+细胞数目增多(术后7 d:73.3±5.75 vs.50.2±6.27 vs.55.5±6.15、132.3±9.81 vs.67.7±9.44 vs.87.0±7.69,P<0.05)及血管密度增加(术后7d:8.3%±0.79%vs.6.97%±0.73%vs.7.31%±0.75%、术后14 d:13.08%±0.79%vs.10.5%±0.70%vs.11.6%±0.67%,P<0.05)。结论外源性SDF-1α可减少脑梗死大鼠的梗死体积,并促进非缺血的远离梗死灶的同侧丘脑VPN内细胞增殖及血管再生,其作用可能通过SDF-1/CXCR4轴实现。
Objective To investigate the possible effects of exogenous stromal cell-derived factor-1α （SDF-1α on cell proliferation and angiogenesis in the ipsilateral thalamic ventroposterior nucleus （VPN） in adult rats with focal conical infarction. Methods Thirty-six hypertensive rats with focal cortical infarction were divided randomly into the SDF-1α group, vehicle group and SDF-1α ± AMD 3100 group, respectively. The rats in the SDF-1α or vehicle group were intraeerebroventricularly injected with recombinant mouse SDF-1α protein （1 μg,/d） or the same volume of 0.9% saline through the trace drug delivery systems daily for 6 consecutive days starting 1 hour after MCAO. The rats in the SDF-1α ± AMD 3100 group were pretreated with AMD 3100 （1 rag/d） intraperitoneally 1 h before SDF-1α administration daily for 6 consecutive days. To label oroliferative cell, BrdU （50 mg/kg） were injected intraoeritoneally before the rats were sacrificed.Animals were sacrificed at 7 or 14 d after stroke. Infarct volume was measured and the expression of BrdU^＋, BrdU^＋/laminin^＋ and microvessels density were detected by immunofluorescence staining. Results At 7 d and 14 d after MCAO, treatment with SDF-1α significantly reduced infarction volume when compared with the vehicle group or SDF-1α ± AMD 3100 group （12.3% ± 0.68% vs. 20.6% ± 1.02% vs. 17.2% ± 0.84% at 7d, and 10.4% ± 0.90% vs. 17.8 %± 0.77% vs.15.0% ± 0.86% at 14d, P〈0.05）. The number of BrdU^＋ cells （132.7 ± 9.11 vs. 90.5 ± 9.35 vs. 96.83 ± 8.01 at 7d, and 264.2 ± 11.65 vs. 192.2 ± 6.18 vs. 207.3 ± 7.53 at 14d, P〈0.05）, BrdU^＋/laminin^＋ cells （73.3 ± 5.75 vs. 50.2 ± 6.27 vs. 55.5 ± 6.15 at 7d, and 132.3 ± 9.81 vs. 67.7 ± 9.44 vs. 87.0 ± 7.69 at 14d, P〈0.05） and microvessels density （8.3% ± 0.79 % vs.6.97% ± 0.73 % vs. 7.31% ± 0.75 %, at 7d, 13.08% ± 0.79% vs. 10.5% ±0.70 vs. 11.6% ± 0.67 % at 14d, P〈0.05） of ipsilateral thalamic VPN were significantly increased in the SDF-1α group when compared with the vehicle group or SDF-1α＋ AMD 3100 group. Conclusions Our results indicate that exogenous SDF-1α reduces infarction volume and promotescell proliferation and angiogenesis in the ipsilateral thalamic VPN, partly through SDF-1/CXCR4 axis.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2013年第10期587-591,共5页
Chinese Journal of Nervous and Mental Diseases
基金
国家自然科学基金资助项目(编号:81188098)
广东省自然科学基金资助项目(编号:9451022002003396)
