rBMSCs/ F92A-Cav1对PAH大鼠的治疗作用及其机制

目的 探讨过表达F92A-丙氨酸替代窖蛋白-1(Cav1)的大鼠骨髓间充质干细胞(rBMSCs/ F92A-Cav1)对肺动脉高压(PAH)大鼠的治疗作用及其机制.方法 予成年雄性Wistar大鼠腹腔注射1%野百合碱(MCT,60 mg/kg)建立PAH模型,建模后2周随机分为3组(10只/组):PAH 组 (仅给予MCT)、Cav1 组 (转导LV-Cav1的rBMSCs)、F92A-Cav1 组(转导LV-F92A-Cav1的rBMSCs),同时设置正常组.基因修饰的rBMSCs(1×106/mL)于尾静脉移植入各组PAH大鼠,移植后3周,采用Image-Pro Plus 6 softwa...

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Published in山东医药 Vol. 57; no. 13; pp. 20 - 23
Main Author 徐聪 夏鹏 杨红莉 唐文强 潘丽 王兰花 陈双峰 张颖新 王乐信 陈海英
Format Magazine Article
LanguageChinese
Published 聊城市人民医院,山东聊城,252000%聊城市人民医院,山东聊城252000 2017
查尔斯特大学生物医学院
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ISSN1002-266X
DOI10.3969/j.issn.1002-266X.2017.13.006

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Summary:目的 探讨过表达F92A-丙氨酸替代窖蛋白-1(Cav1)的大鼠骨髓间充质干细胞(rBMSCs/ F92A-Cav1)对肺动脉高压(PAH)大鼠的治疗作用及其机制.方法 予成年雄性Wistar大鼠腹腔注射1%野百合碱(MCT,60 mg/kg)建立PAH模型,建模后2周随机分为3组(10只/组):PAH 组 (仅给予MCT)、Cav1 组 (转导LV-Cav1的rBMSCs)、F92A-Cav1 组(转导LV-F92A-Cav1的rBMSCs),同时设置正常组.基因修饰的rBMSCs(1×106/mL)于尾静脉移植入各组PAH大鼠,移植后3周,采用Image-Pro Plus 6 software评估肺动脉中膜厚度指数(MT%)、右心肥大指数(RVHI),采用Griess法检测血清NO水平,采用Western blotting法检测肺组织PI3K、AKT蛋白的相对表达量.结果 PAH组MT%、RVHI及肺组织PI3K、AKT蛋白相对表达量均较正常组升高,但血清NO水平降低(P<0.05或<0.01);与PAH组相比,Cav1组、F92A-Cav1组中MT%、RVHI及肺组织PI3K、AKT蛋白相对表达量均降低,而血清NO水平增加,以F92A-Cav1组为著(P<0.05或<0.01).结论 rBMSCs/F92A-Cav1可通过解除野生型Cav1对eNOS的抑制,促进NO释放,从而抑制PAH大鼠肺组织PI3K/AKT通路激活,进而发挥对PAH大鼠的治疗作用.
Bibliography:To investigate the therapeutic effect and mechanism of Caveolin-1 (Cav1) mutant to F92A-Cav1 modified rat bone marrow mesenchymal stem cells (rBMSCs/F92A-Cav1) on rats with pulmonary hypertension (PAH).Methods PAH was induced by intraperitoneal injection of 1% monocrotaline (MCT, 60 mg/kg) in adult male Wistar rats.The PAH rats were randomly divided into four groups (10 rats/group) after 2 weeks of MCT injection: PAH group (only MCT), Cav1 group (transduced with LV-Cav1 modified rBMSCs), F92A-Cav1 group (transduced with LV-F92A-Cav1modified rBMSCs), and the control group.Gene modified rBMSCs (1×106/ml) were transplanted into PAH rats in each group by tail vein injection.After 3 weeks of transplantation, the percentage of media wall thickness (MT%) and right ventricular hypertrophy index (RVHI) were evaluated by Image-Pro Plus 6 software, serum NO concentration was checked by Griess method, and the expression of phosphoinositide 3-kinase(PI3K) and protein kinase B (AKT) was detected by Western blotting.Results
ISSN:1002-266X
DOI:10.3969/j.issn.1002-266X.2017.13.006