聚丙交酯-乙交酯微球搭载鹿茸多肽联合骨髓间充质干细胞对大鼠坐骨神经损伤的修复作用及其机制  

Recovery effect of PLGA microsphere-loaded VAP combined with BMMSCs on sciatic nerve injury of rats and its mechanism

作　　者：龚庆[1] 宋秋莹 邱莉晶[1] 黄晓巍 赵文海[1] GONG Qing;SONG Qiuying;QIU Lijing;HUANG Xiaowei;ZHAO Wenhai(Department of Orthopedics and Traumatology of TCM,Affiliated Hospital,Changchun University of Chinese Medicine,Changchun 130021,China;Department of Otolaryngology,School of Chinese Medicine,Changchun University of Chinese Medicine,Changchun 130117,China;Department of Clinical Pharmacy and Pharmacology,School of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学附属医院中医骨伤科,吉林长春130021 [2]长春中医药大学中医学院耳鼻喉科,吉林长春130117 [3]长春中医药大学药学院临床药学与药理教研室,吉林长春130117

出　　处：《吉林大学学报（医学版）》2018年第6期1174-1178,共5页Journal of Jilin University：Medicine Edition

基　　金：吉林省中医药管理局中医药科技项目资助课题(2017211)

摘　　要：目的:观察聚丙交酯-乙交酯(PLGA)微球搭载的鹿茸多肽(VAP)联合骨髓间充质干细胞(BMMSCs)对大鼠坐骨神经损伤的修复作用,探讨其相关作用机制。方法:横断法复制大鼠外周神经损伤模型。60只大鼠随机分为坐骨神经横断对照组(对照组)、VAP微球组(VAP组)、BMMSCs移植组(BMC组)和VAP微球联合BMMSCs移植组(VAP-BMC组),每组15只。造模7d后,对照组大鼠在横断坐骨神经区域注射PBS溶液,VAP组大鼠在相同位置注射含有载药PLGA微球的PBS溶液,BMC组大鼠注射含有BMMSCs的PBS溶液,VAP-BMC组大鼠注射含有载药PLGA微球和BMMSCs的PBS溶液。3个月后采用Basso、Breattie和Bresnahan (BBB)运动评级量表评估各组大鼠的神经功能,HE染色检测各组大鼠坐骨神经组织形态表现,Western blotting法检测各组大鼠坐骨神经组织中二硫键异构酶(PDI)、葡萄糖调节蛋白78 (GRP-78)和半胱胺酸蛋白酶12 (Caspase-12)蛋白表达水平。结果:BBB运动评级量表评估,与对照组比较,VAP组、BMC组和VAP-BMC组大鼠BBB评分升高(P<0.01),以VAP-BMC组大鼠BBB评分升高最明显。HE染色,与对照组比较,VAP组、BMC组和VAP-BMC组大鼠坐骨神经纤维更粗,轴突直径更长(P<0.01)。Western blotting法检测,与对照组比较,VAP组、BMC组和VAP-BMC组大鼠坐骨神经组织中PDI和Caspase-12蛋白表达水平明显降低(P<0.01),VAP-BMC组大鼠坐骨神经组织中GRP-78蛋白表达水平明显升高(P<0.01)。结论:PLGA微球搭载VAP联合BMMSCs可促进受损坐骨神经的修复,其作用机制可能与抑制内质网应激有关联。Objective:To observe the recovery effect of polylactide-glycolic acid(PLGA)microsphere-loaded velvet antler peptide(VAP)combined with bone marrow mesenchymal stem cells(BMMSCs)on the sciatic nerve injury of the rats,and to explore the related mechanisms.Methods:The sciatic nerve injury models were made by the cross-sectional method.A total of 60 rats were randomly divided into sciatic nerve transection control group(control group),VAP group,BMMSCs transplantation(BMC)group and VAP microsphere combined with BMMSCs transplantation(VAP-BMC)group(n=15).Seven days after modeling,the rats in control group were injected with PBS solution in the transecting sciatic nerve region,the rats in VAP group were injected with PBS solution containing PLGA microspheres loading drug,the rats in BMC group were injected with PBS solution containing BMMSCs,and the rats in VAP-BMC group were injected with PBS solution containing PLGA microspheres loading drug and BMMSCs.After three months,the neurological function of the rats in various groups were evaluated by Basso,Beattie,Bresnahan(BBB)functional sports rating scale,and the morphology of sciatic nerves of the rats in various groups were detected by HE staining.The expression levels of protein disulfide isomerase(PDI),glucose regulated protein-78(GRP-78)and Caspase-12 in sciatic nerve of the rats in various groups were detected by Western blotting method.Results:The results of BBB functional sports rating scale showed that compared with control group,the BBB scores of the rats in VAP group,BMC group and VAP-BMC group we re increased(P<0.01),especially in VAP-BMC group.The results of HE staining showed that compared with control group,the sciatic nerve fibers of the rats in VAP group,BMC group and VAP-BMC group got thicker and the diameters of axon were longer(P<0.01).The results of Western blotting showed that compared with control group,the expression levels of PDI and Caspase-12 in the sciatic nerve of the rats in VAP group,BMC group and VAP-BMC group were significantly decreased

关 键 词：聚丙交酯-乙交酯微球 鹿茸多肽 坐骨神经 内质网应激 骨髓间充质干细胞 

分 类 号：R651.3[医药卫生—外科学]