论文部分内容阅读
目的探讨不同数目骨髓间充质干细胞(mesenchymal stem cells,MSCs)移植对野百合碱(MCT)诱导大鼠肺动脉高压的治疗作用,以及对内皮素-1(endothelin-1,ET-1)表达的影响。方法成年雄性Wistar大鼠40只(体重180～250 g),按随机数字表法分为4组,每组10只。A组:大鼠腹腔注射MCT 60 mg/kg,经颈外静脉注入1×106MSCs;B组:大鼠腹腔注射MCT 60 mg/kg,经颈外静脉注入5×105MSCs;MCT组:大鼠腹腔注射MCT60 mg/kg和等量磷酸盐缓冲液(PBS);对照组:大鼠腹腔注入等量生理盐水和等量PBS。MSCs移植4周后测定右心室收缩压(RVSP),计算心室比,即右心室/(左心室+室间隔)[RV/(LV+VS)];观察肺组织形态学改变;检测肺组织ET-1基因表达和血清ET-1的含量。结果 MSCs移植4周后,A组RVSP和RV/(LV+VS)与MCT组比较明显降低[(35.8±4.2)mm Hg vs.(47.2±10.1)mm Hg,P<0.01;(0.357±0.032)vs.(0.452±0.056),P<0.01];而B组与MCT组比较差异无统计学意义(P>0.05)。A组肺小动脉中膜厚度较MCT组明显变薄[(19.7%±3.0%)vs.(26.8%±3.6%),P<0.01];而B组则差异无统计学意义。逆转录酶-聚合酶链反应(RTase-PCR)检测结果显示,MCT组肺组织ET-1 mRNA表达最强,A组肺组织ET-1 mRNA与MCT组比较明显减弱,B组表达与MCT组接近。A组血清ET-1含量与MCT组比较明显减少。结论 MSCs静脉移植对MCT诱导的肺动脉高压具有抑制作用,并能减少肺组织ET-1的mRNA表达及血清ET-1浓度。采用1×106MSCs移植具有较好的治疗作用。
Objective To investigate the therapeutic effects of different numbers of mesenchymal stem cells (MSCs) transplantation on monocrotaline (MCT) -induced pulmonary hypertension in rats and the expression of endothelin-1 (ET-1) influences. Methods Forty adult male Wistar rats (weighing 180-250 g) were randomly divided into 4 groups (n = 10). Group A: MCT 60 mg / kg was injected intraperitoneally into the rats and 1 106 MSCs were injected into the external jugular vein. Group B: MCT 60 mg / kg was injected intraperitoneally into the rats. 5 105 MSCs were injected into the external jugular vein. MCT group: Injection of MCT 60 mg / kg and equal amount of phosphate buffered saline (PBS); control group: rats were injected intraperitoneally with normal saline and an equal volume of PBS. The right ventricular systolic pressure (RVSP) was measured 4 weeks after MSCs transplantation, and the ventricular ratio, RV / (LV + VS) was calculated. Morphological changes of lung tissue were observed. -1 gene expression and serum ET-1 content. Results Compared with MCT group, the RVSP and RV / (LV + VS) in group A decreased significantly ([(35.8 ± 4.2) mmHg vs. (47.2 ± 10.1) mmHg, ) vs. (0.452 ± 0.056), P <0.01]. There was no significant difference between group B and MCT (P> 0.05). The thickness of pulmonary arteries in group A was significantly thinner than that in MCT group [(19.7% ± 3.0%) vs. (26.8% ± 3.6%), P <0.01], while there was no significant difference in group B. The result of RT-PCR showed that the expression of ET-1 mRNA in lung tissue of MCT group was the strongest, the ET-1 mRNA of lung tissue of MCT group was obviously weakened compared with MCT group, and the expression of ET- Close to A group of serum ET-1 levels compared with the MCT group decreased significantly. Conclusion MSCs can inhibit the pulmonary hypertension induced by MCT and can decrease the expression of ET-1 mRNA and the concentration of ET-1 in lung tissue. With 1 × 106MSCs transplantation has a better therapeutic effect.