不同数目骨髓间充质干细胞移植对大鼠肺动脉高压的作用及内皮素-1表达的影响  

The Effect of Different Numbers of Bone Marrow Mesenchymal Stem Cells Transplanted into Rats with Pulmonary Arterial Hypertension and Their Influence on Endothelin-1 Expression

作　　者：赵科研[1,2] 王辉山[1] 侯明晓[1] 柳克祥[2] 孙江滨[2] 韩宏光[1] 

机构地区：[1]沈阳军区总医院心血管外科,沈阳110016 [2]吉林大学第二医院心血管外科,长春130041

出　　处：《中国胸心血管外科临床杂志》2012年第3期298-303,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

摘　　要：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 study the effect of different numbers of bone marrow mesenchymal stem cells （MSCs） transplanted into rats with pulmonary arterial hypertension （PAH） induced by monocrotaline （MCT） and their influence on the expression of endothelin-1 （ET-1 ）. Methods Forty healthy male Wistar rats （weight, from 180 to 250 g） were divided into four groups by random number table （n= 10 ） ： group A： Wistar rats were intraperitoneally injected with MCT 60 rag/ kg, and then injected with 1 × 10^6 MSCs via the external jugular vein; group B： Wistar rats were intraperitoneally injected with MCT 60 mg/kg, and then injected with 5 × 10^5 MSCs via the external jugular vein; MCT group： Wistar rats were intraperitoneally injected with MCT 60 mg/kg, and then injected with equal amount of PBS via the external jugular vein; control group： Wistar rats were intraperitoneally injected with equal amount of saline and then injected with equal amount of PBS via the external jugular vein. Four weeks after MSCs transplantation, right ventricular systolic pressure （RVSP） and ventricular weight ratio of right ventricle/（left ventricle-t-ventricular septum） were measured. Histomorphology of lung tissue was observed. Genetic expression of ET-1 in lungs and serum peptide of ET-1 were also measured. Results Four weeks after MSCs transplantation, both RVSP and ventricular weight ratio decreased significantly in rats of group A compared with those of MCT group （RVSP： 35.8±4. 2 mm Hg vs. 47.2± 10. 1 mm Hg, P 〈 0. 01 ; ventricular weight ratio： 0. 357±0. 032 vs. 0.452±0. 056, P 〈 0.01）, but these two parameters didn＇t decrease significantly in rats of group B （P 〉 0. 05）. By histopathological staining, the percentage of medial wall thickness of the pulmonary arterioles was significantly less in rats of group A than that of MCT group （19. 7%±3.0% vs. 26.8%±3.6%, P 〈 0.01 ）. There was no statistical difference in the percentage of medial wall thickness of the pulmonary arterio

关 键 词：骨髓间充质干细胞 肺动脉高压 野百合碱 细胞移植 

分 类 号：R543.2[医药卫生—心血管疾病]