携带人端粒酶反转录酶基因脐血间充质干细胞移植治疗肺动脉高压

Umbilical cord blood mesenchymal stem cells carrying human telomerase reverse transcriptase for pulmonary arterial hypertension

背景:保护机体肺血管的内皮细胞,是降低肺循环压力,预防肺动脉高压的重要环节。目的:观察携带人端粒酶反转录酶基因的脐血间充质干细胞移植对大鼠肺动脉高压的治疗作用。方法:体外进行脐血间充质干细胞的培养及纯化,在腺病毒介导下使人端粒酶反转录酶基因成功导入脐血间充质干细胞。将60只SD大鼠随机分成3组:肺动脉高压组、空腺病毒组、腺病毒转染组,每组20只,腹腔注射野百合碱进行肺动脉高压模型复制后,于颈内静脉分别注射1 mL的伊戈尔低糖培养基(L-DBEB),1 mL(1.5×1010 L-1)脐血间充质干细胞悬液,1 mL(1.5×1010 L-1)腺病毒介导下人端粒酶反转录酶基因转染的脐血间充质干细胞悬液。移植21 d后检测各组大鼠血流动力学水平、血浆内皮素1水平以及右心室的肥大指数。结果与结论:各组大鼠动脉血压差异无显著性意义(P>0.05);与肺动脉高压组及空腺病毒组比较,腺病毒转染组大鼠肺动脉收缩期压力、平均肺动脉压均降低,差异有显著性意义(P<0.05);腺病毒转染组大鼠右心室肥大指数与肺动脉高压组及空腺病毒组相比较,差异均无显著性意义(P>0.05);腺病毒转染组大鼠血浆内皮素1水平明显低于肺动脉高压组及空腺病毒组,差异有显著性意义(P<0.05)。结果表明携带人端粒酶反转录酶基因的脐血间充质干细胞移植后,能够改善大鼠机体血流动力学异常状态,还可以保护机体血管内皮细胞。

BACKGROUND: To protect the pulmonary vascular endothelial cells in the body is an important part to reduce pulmonary circulation pressure and prevent pulmonary hypertension.OBJECTIVE: To observe the therapeutic efficacy of umbilical cord blood mesenchymal stem cell transplantation carrying human telomerase reverse transcriptase(hT ERT) in the treatment of pulmonary hypertension in rats.METHODS: Umbilical cord blood mesenchymal stem cells were cultured, purified and transfected with adenovirus carrying hT ERT gene. Sixty Sprague-Dawley male rats were randomly divided into model group, blank adenovirus group, adenoviral delivery group, with 20 rats in each group. Then, the rats were respectively injected via the jugular vein with 1 mL L-DBEB, 1 mL umbilical cord blood mesenchymal stem cell suspension(1.5×1010/L), and 1m L h TERT-transfected umbilical cord blood mesenchymal stem cell suspension(1.5×1010/L) after models of pulmonary hypertension were established via intraperitoneal injection of monocrotaline. After 21 days of transplantation, hemodynamic changes, plasma endothelin 1 levels and the hypertrophy index of the right ventricle were detected.RESULTS AND CONCLUSION: There was no difference in arterial blood pressure among the three groups(P < 0.05). In the adenoviral delivery group, the systolic pressure of the pulmonary artery, mean pulmonary artery pressure and plasma endothelin 1 level decreased significantly as compared with the model group, blank adenovirus group(P < 0.05); but no difference was found in the hypertrophy index of the right ventricle(P > 0.05).These findings indicate that umbilical cord blood mesenchymal stem cell transplantation carrying hT ERT gene can improve the hemodynamic abnormalities in the body and also protect vascular endothelial cells in the body.