Combination therapy with human umbilical cord mesenchymal stem cells and angiotensin‐converting enzyme 2 is superior for the treatment of acute lung ischemia–reperfusion injury in rats. (10th March 2015)

• Record Type: Journal Article
• Authors: Zhang, Xiaomiao; Gao, Fengying; Yan, Yunqi; Ruan, Zheng; Liu, Zhenwei
• Is Part Of: Cell biochemistry and function. Volume 33:Number 3(2015:Apr.)
• Page Start: 113
• Page End: 120
• Publication Date: 2015-03-10
• Subjects: Cytochemistry -- Periodicals; Cell metabolism -- Periodicals; Biochemistry -- Periodicals; Cytology -- Periodicals; 572
• DOI: 10.1002/cbf.3092
• Languages: English
• ISSNs: 0263-6484

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Acute lung ischemia–reperfusion injury (ALIRI) is a serious disease that seriously affects human's life. In this study, we aimed to explore a more effective treatment method by combining human umbilical cord mesenchymal stem cells (HUMSCs) and angiotensin‐converting enzyme 2 (ACE2) for ALIRI. Fifty rats were firstly divided into five groups, namely sham surgery group (sham) and four model groups (model, ACE2, HUMSCs and HUMSCs + ACE2) that were reperfused with 0.1 ml physiological saline (PS), 0.1 ml PS containing 1 × 10<sup>6</sup> lentiviral‐ACE2/HUMSCs/ACE2 + UMSCs, respectively. Quantitative reverse transcription‐PCR (qRT‐PCR) and western blot assays were then conducted to detect the messenger RNA (mRNA) and protein levels of inflammatory cytokines [intercellular adhesion molecule 1 (ICAM‐1), vascular cell adhesion molecule 1 (VCAM‐1), tumour necrosis factor <italic>α</italic> (TNF‐<italic>α</italic>), nuclear factor κB (NF‐κB), platelet‐derived growth factor (PDGF) and angiotensin II (Ang II)], antioxidant proteins [NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO‐1)], DNA damage and apoptotic indicators [BCL2‐associated X (Bax), cleaved caspase‐3 (C‐Csp 3), cleaved‐poly(ADP‐ribose) polymerase (C‐PARP), Y‐H2AX], anti‐apoptotic indicator (Bcl‐2) and smooth muscle cell proliferation indicator [connexin 43 (Cx43)]. According to the qRT‐PCR and western results, the mRNA and protein expression levels of ICAM‐1, VCAM‐1, TNF‐<italic>α</italic>, NF‐κB, PDGF, Bax, C‐Csp 3, C‐PARP and Y‐H2AX were significantly higher in model group than those in sham group and they were significantly reduced by HUMSCs or ACE2 treatment (<italic>P</italic> < 0.05). On the contrary, Bcl‐2 showed an opposite expression trend with the previous proteins. The mRNA and protein levels of NQO1 and HO‐1 were sequentially increased in sham, model, ACE2, HUMSCs and HUMSCs + ACE2 groups. Besides, HUMSCs combined with ACE2 exhibited a better inhibition effect on ALIRI than HUMSCs or ACE2 alone (<italic>P</italic> < 0.05). In summary, HUMSCs combined with ACE2 was demonstrated to have the best therapeutic effect on ALIRI through anti‐inflammation, oxidative stress and anti‐apoptotic processes. Copyright © 2015 John Wiley & Sons, Ltd.</p> </abstract>