牛磺熊去氧胆酸联合骨髓间充质干细胞移植对大鼠脊髓损伤的修复作用  

Repair effects of tauroursodeoxycholic acid in combination use with bone marrow mesenchymal stem cells transplantation on a rat model of spinal cord injury

作　　者：文雅倩 梁超伦 郑坤锐 谢典翁 杨海梅 邹梦迪 郭达 李兴 WEN Ya-qian;LIANG Chao-lun;ZHENG Kun-rui;XIE Dian-weng;YANG Hai-mei;ZOU Meng-di;GUO Da;LI Xing(School of Physical Education and Health,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Guangzhou University of Chinese Medicine,Guangzhou 510000,China;The Second Hospital Affiliated to Guangzhou University of Chinese Medicine,Guangzhou 510000,China)

机构地区：[1]广州中医药大学体育健康学院,广东广州510006 [2]广州中医药大学,广东广州510000 [3]广州中医药大学第二附属医院,广东广州510000

出　　处：《中成药》2025年第1期66-72,共7页Chinese Traditional Patent Medicine

基　　金：广东省自然科学基金(2022A1515010793);广东省中医院拔尖人才科研专项资助(BJ2022KY07);广东省中医院优秀青年人才科研专项资助(SZ2022QN05)。

摘　　要：目的探讨牛磺熊去氧胆酸联合骨髓间充质干细胞移植对大鼠脊髓损伤的修复作用。方法将大鼠随机分为假手术组、模型组、牛磺熊去氧胆酸组、骨髓间充质干细胞组和联合干预组,采用Allen’s法建立脊髓损伤(SCI)模型。造模后次日,牛磺熊去氧胆酸组和联合干预组大鼠灌胃200 mg/kg牛磺熊去氧胆酸;造模后第3天,骨髓间充质干细胞组和联合干预组大鼠尾静脉注射1 mL第三代骨髓间充质干细胞(1×10^(6)/mL);假手术组和模型组大鼠则持续14 d生理盐水灌胃并后续尾静脉PBS注射。造模后第3、7、14天,观察大鼠后肢运动功能并进行BBB评分。给药结束后,通过足迹实验记录大鼠后肢运动轨迹,Western blot法检测脊髓组织IL-6、IL-10、Arg-1、PI3K、Akt蛋白表达,HE染色和Nissl染色观察脊髓组织病理变化,免疫荧光染色检测MAP2、GAP43、GFAP表达。结果与模型组比较,牛磺熊去氧胆酸组、骨髓间充质干细胞组和联合干预组大鼠后肢功能、脊髓组织形态学均有改善(P<0.05),MAP2、GAP43荧光强度和IL-10、Arg-1、p-PI3K、p-Akt蛋白表达升高(P<0.05),GFAP荧光强度和IL-6蛋白表达降低(P<0.05),其中联合干预组效果更佳(P<0.05)。结论牛磺熊去氧胆酸联合骨髓间充质干细胞移植可能通过激活PI3K/Akt信号通路,降低炎症反应,减轻继发损伤,促进轴突和髓鞘再生,达到恢复大鼠脊髓损伤功能的作用。AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen’s method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1×10^(6)/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P<0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P<0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P<0.05);among which the combination therapy group took the lead(P<0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary inj

关 键 词：牛磺熊去氧胆酸 骨髓间充质干细胞 脊髓损伤 炎症 PI3K/AKT信号通路 

分 类 号：R285.5[医药卫生—中药学]