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Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia, as well as survival, differentiation, and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI). MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope, and by using flow cytometry following culture in serum-free medium and exposure to hypoxia (5% CO(2), 95% N(2)) for 12 h with or without TMZ. Thirty Wistar rats were divided into 3 groups (n=10 each group), including group I (AMI control), group II (MSCs transplantation alone), and group III (TMZ+MSCs). Rat MSCs (4×10(7)) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation. The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg·kg(-1)·day(-1)) from day 3 before AMI to day 28 after AMI. Cardiac structure and function were assessed by echocardiography at 28th day after transplantation. Blood samples were collected before the start of TMZ therapy (baseline), and 24 and 48 h after AMI, and inflammatory cytokines (CRP, TNF-α) were measured. Then the survival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining. The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay. Furthermore, apoptosis-related proteins (Bcl-2, Bax) within the post-infarcted myocardium were detected by using Western blotting. In hypoxic culture, the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment. In vivo, cardiac infarct size was significantly reduced, and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group. Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis, further increased MSCs viability, further decreased infarct size, and further improved cardiac function as compared with MSCs alone. The baseline levels of inflammatory cytokines (CRP, TNF-α) had no significant difference among the groups. In contrast, all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group. Furthermore, Western blotting indicated that the expression of anti-apoptotic protein Bcl-2 was up-regulated, while the pro-apoptotic protein Bax was down-regulated in the TMZ+MSCs group, compared with that in the MSCs group. It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.
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Objective To observe the rat cardiac size and cardiac function changes before and after trimetazidine administration plus bone-marrow stem cells transplanting through echocardiography.Methods Forty wistar rats were divided into the following 4 groups randomly:control group (T),myocardial infarction group (Ⅱ),bone marrow stem calls transplantation group (Ⅲ),and bone marrow stem cells transplantation plus trimetazidine administration group(Ⅳ).The rats' left anterior coronary artery in group Ⅱ,Ⅲ and Ⅳwas ligated to produce myocardial infarction model,then bone-marrow stem cells were injected around the infarcted area into the later two groups.Furthermore,rats in group Ⅳ were administrated with trimetazidine.The size and systolic function of the hearts were measured 4 weeks after transplantation.The left ventricular systolic pressure(LVSP) and the end-diastolic pressure(LVEDP) were also measured at the end of experiment.Results The left ventricular diameter of rats in group Ⅲ and Ⅳ was smaller than that in group Ⅱ,and the ventricular systolic function increased,LVSP increased and LVEDP decreased statistically in group Ⅲ and Ⅳ.the amelioration of cardiac size and function was significantly notable in group Ⅳ than that in group Ⅲ.Conclusions Bone marrow stem cells transplantation can release the enlargement of left ventricle and improve cardiac function after myocardial infarction.The therapeutic efficacy can be further elevated if administrated with trimetazidine simultaneously.
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Objective: Recent studies have shown that cell implantation can replace infarcted myocardium to improve cardiac performance. The present study was designed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation into myocardium bordering the infarction with or without induced by 5-azacytidine on cardiac function after acute myocardial infarction (AMI) in rabbits. Methods: AMI was replicated by ligating the left anterior descending coronary artery. Rabbits were randomly divided into three groups: (1) BM -MNC induced by 5-azacytidine implantation (n=7), (2) BM-MNC implantation alo ne (n=7), and (3) AMI control (n=7). In addition, sham-operated (n=5) rabbit s were randomly selected to serve as non-infarction control. Animals for cell im p lantation were received intramyocardial injection of autologous BM-MNC in myoca rdium bordering the infarction, and echocardiography and hemodynamic studies wer e performed to evaluate cardiac function following 28 days of implantation. Results: Compared with the sham-operated group, the left ventricle (LV) end diastolic pressure (LVEDP) was significantly increased (P0.05). Conclusion: BM-MNC induced by 5-azacytidine implantation into myocardium bordering the infarction can significantly improve impaired cardiac function associated with LV remodeling after AMI, however such improvement is not further promoted compared with that in BM-MNC implantation group alone.
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AIM: To evaluate the different conditions inducing mouse embryonic stem cells (ESC) in vitro to differentiate into cardiomyocytes. METHODS: BRL conditioned medium was used to promote the growth of ESC and maintain them in an undifferentiated state. During the inducing process, retinoic acid (RA), DMSO, activin-A and TGF-? 1 were used as inducing reagents, and made up six kinds of differentiating medium. Then a three-step method inducing ESC cultured in hanging drops, in suspension and in plating was used to induce the differentiation of ESC. RESULTS: ESC were induced in vitro to differentiate into cardiomyocytes. Of all groups, the highest differentiating rate was observed in the group induced by activin-A (20 ?g/L) and TGF-? 1 (2 ?g/L). CONCLUSION: The inducing conditions including activin-A (20 ?g/L) and TGF-? 1 (2 ?g/L) is very valuable in inducing ESC differentiation into cardiomyocytes. [
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Objective To examine whether activation of nuclear factor-?B (NF-?B) exists in skin lesions of patients with systemic lupus erythematosus (SLE ) and its association with disease activity. Methods The skin lesions were inves tigated histopathologically in patients with SLE, and NF-?B activation was ass essed by immunohistochemical analysis semi quantitatively. Results Expression o f NF-?B was found on skin lesions in 14 of 15 patients with SLE, including 8 s trong positive (), 3 moderate positive (), and 3 mild positive (+). Brown-coloured particles were mainly distributed in keratinocytes, especially in prick le cells and granular layer cells, as well as in mononuclear cells of dermis. Th ere was no correlation between NF-?B activation and disease activity. However, NF-?B was not detected in skin lesions of all patients with non-SLE and heal thy controls. Conclusions NF-?B activation may be associated with the developm ent of skin lesions in patients with SLE,and not with disease activity.
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AIM: To investigate whether valsartan inhibits the development of atherosclerosis in cholesterol-fed rabbits and its possible mechanism. METHODS: Male rabbits were fed either: (1) normal rabbit chow for 16 weeks; (2) 1.5% cholesterol diet for 16 weeks; or (3) 1.5%cholesterol diet for 16 weeks supplemented by valsartan(3 mg?kg -1?d -1) for the last 4 weeks. After 16 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. RESULTS: Rabbits fed with cholesterol-rich diet showed higher serum lipids levels(P
