Abstract： Stem cell paracrine has been considered as the main mechanism to promote infarcted myocardium regeneration and repair of damaged cardiomyocytes. With further research, secreted frizzled-related protein 2 （Sfrp 2） and stem cell paracrine are closely linked to each other. Sfrp 2 can competitively bind to the specific receptor Fz in Wnt signaling pathway, inhibit Wnt signaling pathway to regulates apoptosis, differentiation, and other life processes of stem cells, and therefore becomes a research hotspot in recent years. This review focuses on the mechanism of Sfrp 2/Wnt signal way in stem cell therapy for myocardial infarction.
Objective To study the effect of bone marrow mesenchymal stem cells(MSCs) implantation into infarcted myocardium on cytokine secretion and angiogenesis. Methods 24 Guizhou xiang porcine were equally divided into experimental group and control group randomly. Three ml bone marrow was extracted from the posterior superior iliac spine. MSCs were cultured according to the methods of Wakitani’s. After being co-cultured with 5-azacytidine for 24 hours, these cells were labeled with bromodeoxyuridine(BrdU). Autologus MSCs were implanted into the acute myocardial infarct site both via the distal segment of the ligated left anterior descending artery (LAD) and topical injection. 3 amp; 6 weeks after transplantation, the samples from experimental group and control group were collected to detect the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and Ⅷ factor by immunohistology and video image digital analysis system. Results The expression of VEGF, bFGF and the microvessel counts in the experimental group were much higher than those of control group (Plt;0.01) at 3 and 6 weeks after transplantation. Conclusion MSCs, after being implanted into infarcted myocardium, shows the ability of secreting VEGF, bFGF, with subsequent angiogenesis.
Objective To study the short and medium term effect of myocardial contractile force by implantation of endothelial progenitor cells （EPCs） in the myocardial infarction model. Methods Hundred and twenty SD rats were equally and randomly divided into experimental group and control group （60 rats in each group）. Acute myocardial infarction model was created by ligation of LAD. Autologous EPCs were purified from peripheral blood then implanted into the acute myocardial infarct site via topical injection. IMDM were used in control group. Specimens and muscle strip were harvested at 3, 6 weeks, 6, 8 and 12 months after EPCs implantation for contractile force study and to detect the expression of vascular endothelial growth factor（VEGF）, basic fibroblast growth factor （bFGF） and Ⅷ factor by immunohistology and video image digital analysis system. Results The expression of VEGF, bFGF and the microvessel counts in experimental group were much higher than those of control group（P〈 0.01） at 3, 6 weeks and 6 months after transplantation. The contractile force in experimental group was better than that in control group（P〈0.01） at the same time. But from 8 months after implantation, the contractile force and so on were not up in the experimental group. Conclusion EPCs, after being implanted into infarct myocardium, shows the ability of improvement of the contractile performance in infarcted myocardium by means of angiogenesis and vasculogenesis and the medium term results are persistent.
Objective To explore the induction of cardiomyogenesis of microRNA-129 （mir-129） in rat bone marrowmesenchymal stem cells （BM-MSCs） and its mechanism. Methods BM-MSCs were isolated from Sprague-Dawley rats and cultured in vitro. Overexpression of mir-129 or both mir-129 and glycogen synthase kinase-3β （GSK-3β） in BM-MSCs was produced with a lentiviral vector system. All the BM-MSCs were divided into four groups: control group （MSCs），Lentiviral vectors＋MSCs group （Lv-MSCs），mir-129 transfection group （mir-129-MSCs），and mir-129＋GSK-3βdouble transfection group （mir-129＋GSK-3β-MSCs）. Five-Azacytidine （5-Aza） （10 μmol/L） was used to induce BM-MSCsdifferentiation into cardiomyocytes. On the 1st，5 th，10 th，15 th and 20 th day after induction，realtime-PCR was performedto detect mRNA levels of GATA-4，Nkx2.5 and MEF-2C. On the 10 th，15 th and 20 th day after induction，Western blottingwas performed to examine expression levels of cTnI，Desmin，GSK-3β，phosphorylated β-catenin and dephosphorylated β-catenin. Results Compared with the control group，at respective time points，mRNA levels of cardiomyogenic genes and expression levels of cardiomyocyte-related proteins of mir-129 transfection group were significantly elevated，theexpression level of GSK-3β was significantly decreased，and the ratio of dephosphorylated/phosphorylated β-catenin was significantly elevated. When both mir-129 and GSK-3β were overexpressed in BM-MSCs，mRNA levels of cardiomyogenicgenes and expression levels of cardiomyocyte-related proteins were significantly lower than those of mir-129 transfection group，and the ratio of dephosphorylated/phosphorylated β-catenin was significantly decreased. Conclusion Overexpression of mir-129 can promote cardiomyogenesis of rat BM-MSCs possibly via inhibiting GSK-3β production and thus decreasing the inhibition of phosphorylation of β-catenin which then enters the nucleus and activates downstream signaling pathways that regulate cardiomyogenic differentiation of BM-MSCs.
ObjectiveTo investigate the effect of miR-190a-5p on the polarization of bone-marrow-derived macrophage (BMDM) induced by lipopolysaccharides to M1- and M2-types.MethodsBMDM (M1-type) induced by bacterial lipopolysaccharide was a M1 group. The macrophage M1-type interfered with negative control miRNA mimics was a NC group. miR-190a-5p mimics interfered with the M1-type of macrophages in the miR-190a-5p group. Morphological changes of macrophages were observed under a microscope, and the proportion of M2-type macrophages (CD206+, F4/80) was detected by flow cytometry. The mRNA expression levels of argininase-1 (Arg1), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), target gene C/EBPα and PU.1 were detected by fluorescence quantitative PCR to verify whether C/EBPα and PU.1 were potential target genes of miR-190a-5p. The expression of pathway proteins C/EBPα and PU.1 were detected by Western blotting.ResultsAfter miR-190a-5p mimics interfered with macrophage M1-type, the antenna of macrophages elongated and showed long cord M2-type cell morphological characteristics. miR-190a-5p mimics interfered with M1-type macrophages for 24 h, and the percentage of M2-type macrophages increased significantly (P<0.05). Effects of miR-190a-5p simulator on mRNA expression levels of M1-type macrophages included: the expression of iNOS and TNF-α was significantly decreased (P<0.05), the expression of Arg1 marked by M2 macrophages was significantly increased (P<0.05), and the mRNA expression levels of target genes C/EBPα and PU.1 were significantly decreased (P<0.05). Western blotting results showed that the overexpression of miR-190a-5p significantly inhibited the protein expressions of C/EBPα and PU.1, while the miR-190a-5p inhibitor increased the expressions of both proteins.ConclusionmiR-190a-5p can promote the polarization of BMDM from M1-type to M2-type.
Objective To study the influence of autologous bone mesenchymal stem cells (BMSCs) on myocardial structure and cardiac function after being implantated into acute infarcted myocardial site. Methods Bone marrow was aspirated from the posterosuperior iliac spine of Guizhou Xiang swine. After being isolated, cultured and co cultured with 5 azacytidine, either autologous BMSCs (total cells 2×10 6, experimental group, n =12), or a comparable volume of culture medium (control group, n =12), was injected into the left anterior descending(LAD) branch of coronary artery just distal to the ligation site of the LAD. The same volume of BMSCs or culture medium was injected into several spots in the infarcted myocardium. Echocardiographic measurements were performed three or six weeks after implantation to assess the myocardial structure and cardiac function. Results Left ventricular function, including eject fraction(EF), fractional shortening and wall thickening, were higher in experimental group when compared with control group. The thickness of the ventricular wall and septum was also found increased while the left ventricular chamber size was smaller in experimental group. Conclusion Implantation of BMSCs into the infarcted myocardium is believed to attenuate the remodeling process, inhibit the extent of wall thinning and dilatation of the ventricular chamber. BMSCs implantation may also improve the contractile ability of the myocardium and cardiac function.
目的 总结冠心病行不停跳冠状动脉旁路移植术（OPCAB）中，右冠状动脉突发急性缺血事件的处理经验。 方法 2010 年 5 月至 2015 年 5 月我院共行 OPCAB 1 568 例，术中出现右冠状动脉急性缺血事件 22 例，其中男 16 例、女 6 例，年龄（66.5±9.7）岁。 结果 11 例患者于紧急右冠状动脉旁路移植术后、开放桥血管后 ST 段可以逐渐恢复正常，右心功能恢复，心律失常明显减少或消失。2 例患者右冠状动脉旁路移植后仍有右心功能不全表现，但经积极药物处理以及主动脉内球囊反搏（IABP）应用后逐步脱离危险期。1 例患者术后循环仍不稳定，最终于术后 2 d 死亡。总死亡率 4.5%。发生围术期心肌梗死 6 例，全组患者 IABP 应用 3 例。 结论 OPCAB 术中右冠状动脉突发缺血事件更多表现为心律失常，发生率虽低，但在无杂交手术室的情况下能够及时判断并正确处理右冠状动脉突发急性缺血事件至关重要，对患者术后及预后都有较积极的影响。