孔博
中国医学科学院阜外医院 心血管外科
BACKGROUND:Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units. The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS. Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury. Here, our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS.METHODS:Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified. ALI was induced in rats byoleic acid (OA), and MSCs were transplanted intravenously. The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours, 24 hours and 48 hours after OA-injection.RESULTS:The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs. The concentration of tumor necrosis factor-a and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs, whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours, 24 hours and 48 hours after OA-challenge.CONCLUSIONS:Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS. Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.
Chinese medical journal 2012
BACKGROUND:The molecular mechanism of human tetralogy of Fallot (TOF) is incompletely defined. Animal models have suggested that neurotrophic tyrosine receptor kinase 3 (NTRK3) might be associated with the outflow tract defect, similar to that seen in human TOF, however, the expression pattern of NTRK3 in human TOF heart tissues has never been investigated.METHODS:Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were applied to detect NTRK3 mRNA and protein levels in right ventricular outflow tract tissue samples of TOF patients, ventricular septal defect (VSD) patients and normal control infants (n = 10 in each group).RESULTS:qRT-PCR analysis indicated that NTRK3 mRNA levels were significantly decreased in the TOF group compared to the VSD group (0.024 +/- 0.003 vs 0.085 +/- 0.004, P = 0.022) and the normal control group (0.024 +/- 0.003 vs 0.091 +/- 0.002, P = 0.006). Quantitative immunohistochemical analysis showed that NTRK3 protein was mainly localized in the myocardium cytoplasm in all 3 groups. The immunoreactivity of NTRK3 protein was again significantly lower in the TOF group compared to the VSD group (1.42 +/- 0.62 vs 14.12 +/- 1.83, P = 0.023) and the control group (1.42 +/- 0.62 vs 16.25 +/- 2.31, P = 0.008). The expression of NTRK3 in the VSD group and in the control group showed no significant differences at both mRNA and protein levels.CONCLUSIONS:Insufficient expression of NTRK3 is associated with the outflow tract defect of human tetralogy of Fallot and may contribute to the progression of this defect.
Chinese medical journal 2009
BACKGROUND:The physiological differences between fetal and postnatal heart have been well characterized at the cellular level. However, the genetic mechanisms governing and regulating these differences have only been partially elucidated. Elucidation of the differentially expressed genes profile before and after birth has never been systematically proposed and analyzed.METHODS:The human oligonucleotide microarray and bioinformatics analysis approaches were applied to isolate and classify the differentially expressed genes between fetal and infant cardiac tissue samples. Quantitative real-time PCR was used to confirm the results from the microarray.RESULTS:Two hundred and forty-two differentially expressed genes were discovered and classified into 13 categories, including genes related to energy metabolism, myocyte hyperplasia, development, muscle contraction, protein synthesis and degradation, extracellular matrix components, transcription factors, apoptosis, signal pathway molecules, organelle organization and several other biological processes. Moreover, 95 genes were identified which had not previously been reported to be expressed in the heart.CONCLUSIONS:The study systematically analyzed the alteration of the gene expression profile between the human fetal and infant myocardium. A number of genes were discovered which had not been reported to be expressed in the heart. The data provided insight into the physical development mechanisms of the heart before and after birth.
Chinese medical journal 2008
