| 摘要: |
| 目的 观察脑源性营养因子(BDNF)缓释微球对周围神经损伤大鼠的神经保护作用。方法 以聚乳酸-羟基乙酸共聚物(PLGA)为载体材料,采用复乳化溶剂挥发法制备BDNF-PLGA缓释微球。将48只SD大鼠随机分为假手术组、模型组、BDNF组和BDNF-PLGA缓释微球组,每组12只;除假手术外,其他各组大鼠均制备坐骨神经钳夹损伤模型。术后BDNF组神经损伤局部注射1 mL/kg BDNF(30 μg/mL),BDNF-PLGA缓释微球组局部注射1 mL/kg BDNF-PLGA缓释微球(活性BDNF含量30 μg/mL)。每周注射给药1次,共给药4次。观察大鼠的大体形态、步态、关节活动等情况,并进行神经功能行为学评分;术后4周,检查神经传导速度(NCV)、波幅、潜伏期和复合肌肉动作电位(CMAP)的幅度,检查完毕后取坐骨神经损伤部位进行组织病理学观察。结果 BDNF-PLGA缓释微球组坐骨神经损伤大鼠的步态、关节活动等一般状况较模型组明显改善,且优于BDNF组。BDNF-PLGA缓释微球可有效改善大鼠损伤神经功能,到第4周时已基本恢复正常,其神经功能恢复状况快于BDNF组。术后4周,BDNF-PLGA缓释微球组能提高大鼠坐骨神经NCV,增大电位波幅,缩短潜伏期,增大坐骨神经CMAP波幅,提高CMAP恢复率(与模型组比较,P<0.01),且上述指标的改善均优于BDNF组(P<0.05)。BDNF-PLGA缓释微球明显改善坐骨神经髓鞘、轴突、髓神经纤维等组织病理学改变。结论 BDNF-PLGA缓释微球对周围神经损伤大鼠具有显著的神经保护作用。 |
| 关键词: 脑源性神经营养因子 聚乳酸-羟基乙酸共聚物 微球体 周围神经损伤 |
| DOI：10.3724/SP.J.1008.2015.00639 |
| 投稿时间：2015-02-02修订日期：2015-04-21 |
| 基金项目:辽宁省自然科学基金 (201202229). |
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| Protective effect of brain-derived neurotrophic factor-PLGA sustained release microspheres on peripheral nerve injury |
| WANG Xiao-hua1,CHENG Ming-he2,WANG Xin-xia3,WANG Qiang1* |
(1. Department of Pharmacy, No. 202 Hospital of PLA, Shenyang 110003, Liaoning, China;
2. Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;
3. Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
*Corresponding authors) |
| Abstract: |
| Objective To observe the protective effect of brain-derived neurotrophic factor-polylactic-co-glycolic acid (BDNF-PLGA) sustained release microspheres on the peripheral nerve injury of rats. Methods BDNF loaded PLGA microspheres were prepared by double emulsion solvent evolution method. A total of 48 adult SD rats were divided into sham operation group, model group, BDNF group and BDNF-PLGA sustained release microspheres group (n=12); the model of sciatic nerve ring clamp injury was established in the latter three groups. After operation BDNF(30 μg/mL, 1 mL/kg) was injected into the local nerve injury sites for BDNF group and BDNF-PLGA sustained release microspheres (BDNF 30 μg/mL,1 mL/kg)were injected for BDNF-PLGA group, once a week for four weeks. The general status, pace, and joint motion of each group were observed after operation; and the changes of neurological scores, nerve conduction velocity (NCV), amplitude, latency period, compound muscle action potential (CMAP) and histopathology were observed 4 weeks after operation. Results The general status, pace, and joint motion of the sciatic nerve injury in BDNF-PLGA group were significantly improved compared with the model group and BDNF group. The BDNF-PLGA sustained release microspheres effectively improved the functions of injured peripheral nerve, which basically restored the normal level after four weeks, and the recovery was rapid than the BDNF group. The NCV, amplitude and latency period, CMAP amplitude, and recovery rate of CMAP in the BDNF-PLGA group was significantly improved compared with the model group(all P<0.01), and the improvements were also significantly greater than those in group BDNF (P<0.05). The BDNF-PLGA sustained release microspheres also significantly improved the pathology changes of sciatic nerve injury, including those of the myelin sheath, axon and vacuole. Conclusion The BDNF-PLGA sustained release microspheres have prominent protective effect against the peripheral nerve injury in rats. |
| Key words: brain-derived neurotrophic factor polylactic-co-glycolic acid microspheres peripheral nerve injury |
