Lu Yan, Zhang Zhaohua, Cheng Guanghui, Luan Yun
Department of Pathology, Hospital of Beihang University, Beijing 100191, China.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2013 Jun;30(3):601-6.
In the present study, we carried out intratracheal administration of bone marrow-derived mononuclear cells (BM-MNCs) to dehydromonocrotaline (DMCT)-induced canine pulmonary artery hypertension (PH) of rat model to examine the security and feasibility, and the aim was to discuss the mechanism. All animals (n=30) were randomly divided into 3 groups (n=10 in each group), i. e. control group, PH group and BM-MNCs group. Six weeks after the transplantation, the hemodynamic data and right ventricle weight ratio were significantly improved for those in BM-MNCs group compared with those in PH group. The lung mRNA levels of vascular endothelial growth factor (VEGF) were higher, while preproendothelin-1 (ppET-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were lower compared with those in the PH group (P<0. 05). Immunofluorescence and histochemical results confirmed that 6 weeks after the administration, transplanted BM-MNCs were still alive and could differentiate into pulmonary vascular endothelial cells. These results showed that intratracheal administration of BM-MNCs could obviously reduce or even reverse the DMCT induction of PAH process. The mechanism could be explained as that the function was mainly through the paracrine effect to promote renewable and reduce inflammation.
在本研究中,我们对脱氢野百合碱(DMCT)诱导的大鼠犬肺动脉高压(PH)模型进行气管内注射骨髓来源的单核细胞(BM-MNCs),以检查其安全性和可行性,目的是探讨其机制。所有动物(n = 30)随机分为3组(每组n = 10),即对照组、PH组和BM-MNCs组。移植6周后,与PH组相比,BM-MNCs组的血流动力学数据和右心室重量比显著改善。与PH组相比,BM-MNCs组肺组织中血管内皮生长因子(VEGF)的mRNA水平较高,而前内皮素-1(ppET-1)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的mRNA水平较低(P < 0.05)。免疫荧光和组织化学结果证实,给药6周后,移植的BM-MNCs仍然存活,并可分化为肺血管内皮细胞。这些结果表明,气管内注射BM-MNCs可明显减轻甚至逆转DMCT诱导的PAH进程。其机制可能是该功能主要通过旁分泌作用促进再生并减轻炎症。