脂肪间充质干细胞早期干预对野百合碱诱发的肺动脉高压大鼠肺小动脉功能的影响

 目的：观察脂肪间充质干细胞(ADMSCs)早期干预对野百合碱(MCT)诱发的大鼠肺动脉高压(PAH)进程中肺小动脉功能的影响。方法：采用SD大鼠腹股沟皮下脂肪，经胶原酶消化法分离培养ADMSCs。雄性SD大鼠90只，随机分为正常对照组、PAH组和ADMSCs早期干预组(ADMSCs-EI组)。一次性腹腔注射MCT 40 mg/kg建立PAH动物模型。ADMSCs-EI组于MCT注射后1周，经左颈外静脉一次性给予ADMSCs(1×106)。分别于ADMSCs移植后1、2、3周，右心导管法测定大鼠的肺动脉平均压(MPAP)，并采用离体血管张力法检测大鼠肺小动脉的内皮依赖性舒张(EDdR)、非内皮依赖性舒张(EDiR)以及收缩功能(VCF)。收缩或舒张的敏感性用pD2值表示。结果：与对照组比较，腹腔注射MCT后2周，PAH组大鼠肺小动脉EDdR明显减弱；同时，与PAH组比较，ADMSCs早期移植后1周，ADMSCs-EI组大鼠肺小动脉EDdR明显增强（均P<005）。与对照组比较，腹腔注射MCT后3、4周，PAH组大鼠MPAP显著升高，肺小动脉EDdR和EDiR显著减弱；同时，与PAH组比较，ADMSCs早期移植后2、3周，ADMSCs-EI组大鼠MPAP显著降低，肺小动脉EDdR和EDiR显著增强（均P<005）；但是，VCF在3组间均无显著差异（P>005）。结论： ADMSCs早期干预可以明显改善受损的肺小动脉EDdR及EDiR，并有效地降低MCT诱发的PAH大鼠的肺动脉压力。

Effects of early intervention of adipose-derived mesenchymal stem cells on function of pulmonary arterioles in rats with pulmonary arterial hypertension induced by monocrotaline

AIM：To investigate the effects of early intervention of adipose-derived mesenchymal stem cells (ADMSCs) on the function of pulmonary arterioles in monocrotaline (MCT)-induced pulmonary arterial hypertensive (PAH) rats. METHODS：ADMSCs were obtained from subcutaneous adipose tissue in the rat groin region and isolated by collagenase digestion. Ninety male SD rats were randomly divided into normal control group, PAH group and early intervention of ADMSCs (ADMSCs-EI) group. PAH was induced by MCT at dose of 40 mg/kg intraperitoneally. ADMSCs were delivered via left jugular vein 1 weeks after MCT administration. At the 1st, 2nd and 3rd weeks after transplantation of ADMSCs, mean pulmonary arterial pressure (MPAP) was measured by catheterization. Pulmonary arteriolar endothelium-dependent relaxation (EDdR), endothelium-independent relaxation (EDiR) and vasoconstrictive function (VCF) were evaluated by isolated vascular ring tension. The potency of vascular contraction and relaxation was expressed as the pD2 value. RESULTS：Compared with control group, pulmonary arteriolar EDdR in PAH group was obviously decreased 2 weeks after MCT administration. Meanwhile, compared with PAH group,  pulmonary arteriolar EDdR in ADMSCs-EI group was obviously increased 1 week after early transplantation of ADMSCs. Compared with control group, MPAP was significantly increased and pulmonary arteriolar EDdR and EDiR were significantly decreased in PAH group 3 and 4 weeks after MCT administation. Meanwhile, compared with PAH group, MPAP was markedly decreased and pulmonary arteriolar EDdR and EDiR were markedly increased in ADMSCs-EI group 2 and 3 weeks after early transplantation of ADMSCs. However, pulmonary arteriolar VCF was not different among all groups. CONCLUSION：Early intervention of ADMSCs significantly ameliorates the impaired pulmonary arteriolar EDdR and EDiR, and greatly decreases MPAP in MCT-induced PAH rats.