同种异体骨髓基质干细胞移植治疗大鼠肺动脉高压模型的实验研究

摘要

Objective To investigate the effect and action mechanisms of rat bone marrow mysenchymal stem cells (rBMSCs) on the treatment of monocrotaline-induced pulmonary hypertension. Methods The approach of whole bone marrow adherent culture was adopted to isolate rBMSCs. Totally 26 healthy SD rats were randomly divided into three groups. Rats in control group (n = 6) were subcutaneously injected with sodium chloride. Models of pulmonary hypertension (n = 12) were induced by subcutaneously injecting monocrotaline (60 mg/kg). Rats in interference group (n = 8) were subcutaneously injected with monocrotaline (60 mg/kg) and subsequently received rBMSCs (1 × 106/mL 0. 5 mL). Right ventricular pressure (RSVP), right ventricular index [RV/CLV + S)], histology of lung tissues and the level of ET-1 in lung tissues were determined four weeks later. Results RSVP, RV/(LV+S) and ET-1 content were significantly increased in pulmonary hypertension model group as compared with those in the control group (P<0.05). After treatment with rBMSCs, these indexes were dramatically reduced (P<0.05). Histological results showed a significant vascular remodeling in model group; however, this was dramatically suppressed by rBMSCs treatment. Conclusion rBMSCs transplantation decreases ET-1 expression and further inhibits pulmonary vascular remodeling, thus ameliorating the development of pulmonary hypertension.%目的 研究大鼠骨髓基质干细胞(rBMSCs)对大鼠肺动脉高压的治疗作用及其机制.方法 采用有利于rBMSCs生长及增殖的全骨髓贴壁法分离及培养干细胞;利用野百合碱制备肺动脉高压模型.健康SD大鼠26只,6只作为对照组,给予等量生理盐水腹腔注射;12只作为肺动脉高压模型组,每只大鼠腹腔注射野百合碱60 mg/kg;8只作为干细胞治疗组均给予野百合碱(60 mg/kg)腹腔注射,同时给予rBMSCs尾静脉注射.4周后观察大鼠的生长情况,测右心室压力及右心室肥大指数,比较肺脏病理变化及肺组织均浆中内皮素-1(ET-1)含量的变化.结果 模型组大鼠右心室压力、右心室肥大指数、组织中ET-1含量明显高于对照组(P＜0.05);干细胞治疗组较模型组显著降低(P＜0.05);肺组织病理切片显示模型组肺血管重构明显,而治疗组肺血管重构减轻.结论 骨髓基质干细胞可能通过抑制ET-1的产生,从而抑制肺血管重构,显著降低肺动脉高压大鼠模型的右心室压力.