补阳还五汤联合骨髓间充质干细胞移植对大脑中动脉栓塞模型整合素相关因子的影响

背景:前期研究发现,补阳还五汤联合骨髓间充质干细胞移植可发挥协同抗脑缺血损伤作用。目的:分析骨髓间充质干细胞移植联合补阳还五汤促进脑缺血血管新生的作用。方法:将96只SD大鼠随机分为4组,均制作大脑中动脉栓塞模型。联合组于造模前3 d灌胃给予补阳还五汤10 mL/kg,1次/d,造模成功后2 h灌胃1次,以后每12 h灌胃1次;局灶脑缺血2 h再灌注2 h后,干细胞组、联合组向脑室中注入骨髓间充质干细胞悬液,30 min后再注射抗CD34、CD45抗体;抗体组注射抗CD34、CD45抗体;模型组注射生理盐水。联合组于再灌注后12,24,36,48 h进行血清αVβ3水平及脑组织免疫组织化学、Q-PCR、免疫印迹检测,其余3组均于再灌注后36 h检测上述指标。结果与结论:(1)血清αVβ3水平:抗体组血清αVβ3水平低于模型组(P<0.05),干细胞组、联合组高于抗体组(P<0.05),且联合组再灌注不同时间点的血清αVβ3水平高于干细胞组(P<0.01);(2)免疫组织化学:抗体组CD34阳性细胞数量少于模型组(P<0.05),干细胞组、联合组高于抗体组(P<0.05);(3)Q-PCR与免疫印迹检测:与模型组相比,抗体组、干细胞组p FAK蛋白表达水平降低(P<0.05),FAK基因及蛋白表达变化不大;与其他组比较,联合组FAK蛋白(自再灌注后24 h开始)和p FAK蛋白(自再灌注12 h开始)显著升高(P<0.05,P<0.01),且随着再灌注时间延长有逐渐升高趋势;(4)结果表明:骨髓间充质干细胞移植联合补阳还五汤可逆转抗CD34+CD45抗体引起的血管内皮细胞数量减少、整合素αVβ3及其下游信号分子表达下降,促进血管新生。

丹参喷鼻剂对实验性脑缺血的保护作用

目的:研究丹参喷鼻剂对实验性脑缺血的保护作用。方法:采用大鼠MCAO模型分别观察对大鼠脑内梗死面积的影响,对大鼠抗疲劳的影响及大鼠微循环的影响,测定其相关指标。结果:比较于模型对照组神经行为学评分(2.20±0.82),丹参喷鼻剂中剂量组(1.52±0.46)和高剂量组(1.38±0.41)均可显著地改善大鼠的行为障碍(P<0.05);比较于模型对照组(20.86±4.23)%,丹参喷鼻剂高剂量组(14.93±4.27)%可显著性减少大鼠脑梗死面积(P<0.05);丹参喷鼻剂高剂量组大鼠游泳时间(16.51±5.82)min长于模型对照组(9.83±3.15)min,差异有统计学意义(P<0.05);丹参喷鼻剂高剂量组滴Ad后微动脉管径缩小值(2.72±1.53)μm与模型对照组(3.40±3.22)μm相比较,差异也有统计学意义(P<0.05)。结论:丹参喷鼻剂对实验性脑缺血具有保护作用。

GM1 stabilizes expression of NMDA receptor subunit 1 in the ischemic hemisphere of MCAo/reperfusion rat

Objective: To determine the protective effect of monosialoganglionside (GM1) and evaluate the influence of GM1 on expression of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in Sprague-Dawley (SD) rats with focal cerebral ische- mia-reperfusion (I/R). Methods: Left middle cerebral artery (MCA) was occluded by an intraluminal suture for 1 h and the brain was reperfused for 72 h in SD rats when infarct volume was measured, GM1 (10 mg/kg) was given ip (intraperitoneally) at 5 min (group A), 1 h (group B) and 2 h (group C) after MCA occlusion (MCAo). Expression of NMDAR1 was detected by Western blot at various time after reperfusion (4 h, 6 h, 24 h, 48 h and 72 h) in ischemic hemispheres of the rats with or without GM1 admin- istered. Results: (1) Adjusted relative infarct volumes of groups A and B were significantly smaller than that of group C and the control group (P<0.01 and P<0.05, respectively). (2) Expression level of NMDAR1 was temporally high at 6 h after reperfusion, and dipped below the normal level at 72 h after reperfusion. GM1 at 5 min after MCAo significantly suppressed the expression of NMDAR1 at 6 h after reperfusion (P<0.05 vs the control). At 72 h after reperfusion, the NMDAR1 expression level of rats treated with GM1 administered (at 5 min or 2 h after MCAo) was significantly higher than that of the control (P<0.05). Conclusion: GM1 can time-dependently reduce infarct volume in rats with focal cerebral I/R partly through stabilizing the expression of NMDAR1.