脂肪干细胞移植对野百合碱诱发的肺动脉高压大鼠肺动脉压的量效和时效作用  

Effects of dose and timing of adipose-derived stem cell transplantation on pulmonary arterial pressure in monocrotaline-induced pulmonary arterial hypertension in rats

作　　者：郑武洪 罗莉[1] 李玲[1] 练桂丽 许昌声[1] 王华军[1] 谢良地[1] Zheng Wuhong;LuoLi;Li Ling;Lian Guili;Xu Changsheng;Wang Huajun;Xie Liangdi(Fujian Hypertension Research Institution,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院高血压研究所,福州350005

出　　处：《中华细胞与干细胞杂志（电子版）》2018年第6期321-327,共7页Chinese Journal of Cell and Stem Cell（Electronic Edition）

基　　金：国家自然科学基金面上项目(81878537;815704446;81270111)

摘　　要：目的探索脂肪干细胞(ADSC)移植治疗野百合碱(MCT)诱导的肺动脉高压(PAH)大鼠的适宜细胞数和干预时间。方法 (1)MCT的建模时效和量效:雄性SD大鼠48只分为正常对照组,20 mg/kg、30 mg/kg、40 mg/kg MCT组分别予腹腔注射生理盐水、MCT20 mg/kg、30 mg/kg、40 mg/kg,4和8周后,右心室插管法检测平均肺动脉压(mPAP),称重法计算右心室肥厚指数(RVHI)。(2)ADSC的治疗量效作用:雄性SD大鼠分别予腹腔注射MCT(30只)和生理盐水(30只),1周后通过颈静脉注射分别移植0.5×10~6、1.0×10~6、3.0×10~6、5.0×10~6ADSC,其他组予等量生理盐水。移植3周后检测mPAP和RVHI。(3) ADSC的治疗时效作用:雄性SD大鼠30只,分别注射40 mg/kg MCT(24只)和生理盐水(6只)。MCT腹腔注射1 d,1、2周后分别移植1.0×10~6个ADSC。MCT注射4周后检测mPAP和RVHI。多组间比较采用单因素或双因素方差分析,两两比较采用LSD检验。结果 (1)腹腔注射4周后,30 mg/kg或40 mg/kg MCT组mPAP和RVHI均升高[mPAP值(24.89±3.31) mmHg,(27.19±2.11)mmHg比(15.80±0.42)mmHg,差异有统计学意义(P均<0.05);RVHI值0.42±0.06,0.47±0.04比0.25±0.02,差异有统计学意义(P均<0.05)]。8周后,20 mg/kg或30 mg/kg MCT组mPAP和RVHI均恢复正常,而40 mg/kg MCT组大鼠全部死亡。(2) 40 mg/kg MCT诱导的PAH大鼠mPAP和RVHI均升高。移植1.0×10~6个ADSC可降低PAH大鼠的mPAP[(17.24±0.66)mmHg比(27.19±1.73)mmHg,P <0.05]。移植0.5×10~6、3.0×10~6、5.0×10~6个ADSC不能降低PAH大鼠的mPAP和RVHI。(3)MCT腹腔注射1周和2周后,移植1.0×10~6个ADSC可降低PAH大鼠的mPAP。结论 40 mg/kg MCT造模4周可建立稳定的PAH大鼠模型;造模1或2周后移植1.0×10~6个ADSC能有效降低PAH大鼠的mPAP。Objective To investigate the effect of dose and timing of adipose-derived stem cells(ADSC)transplantation on pulmonary arterial pressure in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)in rats.Methods(1)MCT-induced PAH in rats:48 male SD rats were injected intraperitoneally with normal saline,20 mg/kg,30 mg/kg and 40 mg/kg MCT respectively.Mean pulmonary arterial pressure(mPAP)was determined by right heart catheterization and right ventricular hypertrophy index(RVHI)was detected by weighting method at 4 and 8 weeks after MCT injection.(2)Dose of ADSC:male SD rats were administrated with 40 mg/kg MCT(n = 30)and normal saline(n = 30).Normal saline or different numbers of ADSC(0.5×10^6,1.0×10^6,3.0×10^6,5.0×10^6)were injected through jugular vein at 1 week after intraperitoneal injection of MCT.mPAP and RVHI were detected at 3 weeks after ADSC transplantation.(3)Timing of ADSC transplantation:30 male SD rats were administrated with 40 mg/kg MCT(n = 30)and normal saline(n = 6).One day,1 or 2 weeks after intraperitoneal injection of 40 mg/kg MCT,1.0×10^6 ADSC were transplanted into the rats.mPAP and RVHI were detected at 4 weeks after MCT injection.Differences among groups were compared using one-way or two-way analysis of variance,and pairwise comparison was performed using LSD test.Results(1)4 weeks after intraperitoneal injection of 30 or 40 mg/kg MCT,both mPAP and RVHI increased [mPAP(mm Hg):24.89±3.31,27.19±2.11 vs 15.80±0.42,P<0.05;RVHI:0.42±0.06,0.47±0.04 vs 0.25±0.02,P<0.05)].8 weeks after MCT injection,mPAP and RVHI returned to normal in the 20 and 30 mg/kg MCT groups.All rats died in the 40 mg/kg MCT group.(2)Both mPAP and RVHI in the 40 mg/kg MCT group elevated.3 weeks after transplantation of 1.0×10^6 ADSC,mPAP declined(27.19±1.73)mmHg vs(17.24±0.66)mmHg(P<0.05).However,mPAP did not decrease in rats given 0.5×10^6,3.0×10^6 or 5.0×10^6 ADSC.(3)1 or 2 weeks after intraperitoneal injection of 40 mg/kg MCT,mPAP reduced in PAH rats given 1.0×10^6 ADSC.Conclusions 4 weeks afte

关 键 词：脂肪干细胞 肺动脉高压 野百合碱 平均肺动脉压 

分 类 号：R544.1[医药卫生—心血管疾病]