Pioglitazone administration combined with bone marrow mesenchymal stem cells transplantation improved the heart function of rats with myocardial infarction / 中国组织工程研究
Chinese Journal of Tissue Engineering Research
;
(53): 3698-3704, 2015.
Artigo
em Chinês
| WPRIM
| ID: wpr-467242
ABSTRACT
BACKGROUND:
Our previous work has demonstrated that bone marrow mesenchymal stem cels (BMSCs) transplantation can improve the heart function of rats with myocardial infarction. However, the overal efficacy is not satisfactory.OBJECTIVE:
To adopt pioglitazone as a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist combined with BMSCs transplantation therapy, thereby further improving cardiac function of rats with myocardial infarction as wel as investigating the relevant mechanisms.METHODS:
Twenty Sprague-Dawley rats with myocardial infarction were induced by the left anterior descending coronary artery ligation. The animals were randomized into two groups BMSCs and BMSCs+pioglitazone. Two weeks later, al the animals received the injection of BMSCs labeled with PKH26 in PBS into the local infarct zone, and then pioglitazone (3 mg/kg/d) was given by the oral gavage for 2 weeks in the BMSCs+pioglitazone group after the cel transplantation. After 2 weeks of cel transplantation, cardiac functions were evaluated by echocardiography. The expressions of PPAR-γ, Connexin 43 and molecules in TGF-β1/SMAD signaling pathway were examined in different areas of the left ventricle from each harvested heart using immunofluorescent staining, western blot assay and qRT-PCR. RESULTS ANDCONCLUSION:
There were no differences in the baseline parameters of cardiac function between the two groups. At 2 weeks after cel transplantation, the left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole and left ventricular ejection fraction were significantly improved in the BMSCs+ pioglitazone group; the expressions of PPAR-γ and Connexin 43 were distinctly increased in different zones of the left ventricle; the levels of TGF-β1, SMAD2 and SMAD3 were obviously attenuated in the infarct zone and border zone. The above-mentioned findings suggest that pioglitazone, a PPAR-γ agonist, can enhance BMSCs potential in improvingthe heart function after myocardial infarction, and PPAR-γ may elevate the expression of Connexin 43via the blockade of the TGF-β1/SMAD signaling pathway in the procedure.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Tipo de estudo:
Ensaio Clínico Controlado
Idioma:
Chinês
Revista:
Chinese Journal of Tissue Engineering Research
Ano de publicação:
2015
Tipo de documento:
Artigo
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