【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。更多还原

【Abstract】 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 cortical infarction.Methods Thirty-six hypertensive rats with focal cortical infarction were divided randomly into the SDF-1αgroup, vehicle group and SDF-1α + AMD 3100 group, respectively. The rats in the SDF-1α or vehicle group were intra cerebroventricularly injected with recombinant mouse SDF-1α protein(1μg/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 + AMD3100 group were pretreated with AMD 3100(1 mg/d) intraperitoneally 1 h before SDF-1α administration daily for 6 con secutive days. To label proliferative cell, BrdU(50 mg/kg) were injected intraperitoneally 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+/lam inin+and microvessels density were detected by immunofluorescence staining.Results At 7 d and 14 d after MCAO, treat ment 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 ipsi lateral 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 promotes cell proliferation and angiogenesis in the ipsilateral thalamic VPN, partly through SDF-1/CXCR4 axis.更多还原