1.Protective effects of trimetazidine on bone marrow mesenchymal stem cells viability in an ex vivo model of hypoxia and in vivo model of locally myocardial ischemia.
Hongxin, XU ; Gangyan, ZHU ; Yihao, TIAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(1):36-41
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.
2.The expressions and the effects of cystatin C, retinol-binding protein and β2-microglobulin on predicting renal damage in elderly patients with hypertension
Wen LU ; Shuhua LIU ; Ting LI ; Gangyan ZHU ; Zhiming ZHAO
Chinese Journal of Geriatrics 2015;34(5):487-490
Objective To investigate the expressions of serum cystatin C CysC),retinolbinding protein (RBP),serum and urinary β2-microglobulin (β2-MG) and their effects on predicting renal damage in primary hypertension in elderly patients.Methods A total of 149 patients were divided into 3 groups of hypertension grade 1 (n =50),hypertension grade 2 (n =50) and hypertension grade 3 group (n=49).92 healthy controls who took physical examination were selected as control group.The levels of serum CysC,RBP,serum and uric β2-MG,blood urea nitrogen,creatinine and other biochemical indexes were detected.The complications of hypertension were observed.The differences in renal function indexes between groups and their correlations were analyzed.Results There were 86 cases with hyperlipidemia (57.7%),71 cases with atherosclerosis (47.7%),59 cases with type 2 diabetes mellitus (39.6%),56 cases with coronary heart disease (37.6%),and 49 cases with cerebral vascular disease (32.9%) in 149 hypertensive patients.The levels of serum CysC,RBP,serum and uric β2-microglobulin were increased in hypertensive patients as compared with healthy controls (P<0.05 or 0.01),and the extents of increments in the above indexes were positively correlated with blood pressure level [CysC:(1.2± 0.5) mg/L,(1.7±0.6) mg/L,(2.2±0.9) mg/L;RBP:(53.1±10.2) mg/L,(65.2±16.3)mg/L,(75.8±17.5) mg/L;serum β2-MG:(2.7±1.5) mg/L,(4.0±2.1) mg/L,(4.9±2.0) mg/L;uric β2-MG:(178.3±73.9) ng/L,(237.9±78.6) ng/L,(277.5±87.5) ng/L;respectively,P<0.05or 0.01].Conclusions Elderly hypertensive patients are complicated with a variety of diseases.The levels of serum CysC,retinol-binding protein,serum and uric β2 microglobulin have significant diagnostic values on renal impairment caused by hypertension,and can be considered as sensitive factors for early renal impairment in essential hypertension.
3.Effect of health education on diabetics with role lack
Songlin WU ; Shiqi TANG ; Yarong HAO ; Gangyan ZHU
Chinese Journal of Health Management 2012;06(5):315-317
Objective To improve self-management of diabetics with role lack.Methods A total of 121 diabetics with role lack were enrolled and received mass education and individual counseling.Serum levels of glucose and lipid profiles and body mass index (BMI) were assessed and compared before and after intervention by using paired t test.Results Knowledge on diabetes ( 79.37 ± 12.45 vs 31.69 ± 9.36,t =2.860,P < 0.05) and self-management skills ( 9.21 ± 2.85 vs 4.43 ± 1.72,t =2.812,P < 0.05 ) were significantly improved after receiving health education,although fasting plasma glucose [ ( 6.3 ± 1.8 ) vs (8.1 ±2.1) mmol/L,t =2.736,P <0.05],2-h postprandial blood glucose [(8.1 ±3.7) vs (12.8 ±4.1)mmol/L,t =3.549,P < 0.05 ],glycosylated hemoglobin Alc [ (6.4 ± 2.5 ) % vs (7.1 ± 2.7 ) %,t =2.603,P < 0.05 ],total cholesterol [ ( 5.2 ± 2.3 ) vs ( 6.3 ± 2.4 ) mmol/L,t =2.036,P < 0.05 ],triglyceride [(1.7±0.7) vs (2.4±0.8) mmol/L,t=2.368,P<0.05] and BMI [(25.6±6.2) vs (27.3±6.5)kg/m2,t =2.546,P < 0.05 ] were largely decreased.Conclusion Health education could improve selfmanagement and cure of diabetic patient with role lack.
4.Protective Effects of Trimetazidine on Bone Marrow Mesenchymal Stem Cells Viability in an ex vivo Model of Hypoxia and in vivo Model of Locally Myocardial Ischemia
XU HONGXIN ; ZHU GANGYAN ; TIAN YIHAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(1):36-41
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% CO2,95% N2) 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 (4×107) 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.