Objective To systematically evaluate impact of perioperative use of clopidogrel on coronary bypass grafting (CABG) patients for anti-platelet treatment, in order to provide evidence for the rational drug use of such patients in the perioperative period. Methods PubMed, EMbase, HighWire, CENTRAL and its affiliated clinical trial registered data center, CBM and CNKI were electronically searched from 2003 to November, 2012. Randomized controlled trials (RCTs) and non-randomized clinical trials on perioperative use of clopidogrel of CABG patients were collected. References of included studies were also retrieved. Two reviewers independently screened studies according to exclusion and inclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.0 software. Results 18 studies (including 10 RCTs and 8 non-randomized clinical trials) involving 14 592 patients were included. The results of meta-analysis showed that: a) Among 10 included RCTs, preoperative use of clopidogrel for anti-platelet treatment reduced the incidence of myocardial infarction obviously, compared with the blank control group (RR=0.63, 95%CI 0.48 to 0.83, P=0.000 9), but there is no significant difference between the two groups in blood loss amount within 24 hours after operation (MD=130, 95%CI –6.21 to 266.22, P=0.06), the number of reoperation patients because of bleeding (RR=1.42, 95%CI 0.92 to 2.20, P=0.12), and risk of postoperative short-term death (RR=1.19, 95%CI 0.89 to 1.58, P=0.24); b) Among 8 non-randomized clinical trials, there was no significant difference between the two groups in reducing the incidence of myocardial infarction (RR=0.83, 95%CI 0.30 to 2.26, P=0.71), but preoperative use of clopidogrel for anti-platelet treatment significantly increased blood loss amount within 24 hours after operation (MD=82.42, 95%CI 35.18 to 129.66, P=0.000 6), the number of reoperation patients because of bleeding (RR=1.71, 95%CI 1.07 to 2.75, P=0.03), and risk of postoperative short-term death (RR=1.89, 95%CI 1.15 to 3.12, P=0.01). Conclusion Current evidence shows that, perioperative use of clopidogrel can reduce the incidence of myocardial infarction, but doctors should consider cautiously the increased risk of bleeding, re-operation and postoperative short-term death. There is contradiction between the results of RCTs and those of non-randomized clinical trials, which may result from the argument intensity, quantity and sample size bias of the included studies. The above conclusion should be proved by large-scale high-quality RCT results in future.
Objective To elucidate whether glucose transporters-4 （GLUT-4） takes part in glucose uptake of mesenchymal stem cells （MSCs） and whether Akt gene improves translocation and expression of GLUT-4 in MSCs under hypoxic environment ex vivo. Methods MSCs, transfected by Akt gene and no, were cultured with normoxia (5% CO2) or hypoxia (94%N2, 1%O2 and 5% CO2) at 37 ℃ for 8 h. Glucose uptake was assayed by using radiation isotope 2-［3H］-deoxy-Dglucose (3H-G) and the expression of GLUT-4 protein and mRNA was assayed by immunocytochemistry, Western blot and RT-PCR, respectively. Results ①3 H-G intake of MSCs was significantly increased in hypoxiatransfection group than that in hypoxia-non-transfection 〔（1.39±0.13） fold, P＜0.05〕, but which was lower than that in normoxia-non-transfection group, P＜0.05. ②GLUT-4 was expressed by MSCs under any conditions. Compared with normoxia-non-transfection group, hypoxia decreased the expressions of GLUT-4 mRNA and protein significantly (P＜0.05). ③Compared with hypoxianontransfection group, the expression of GLUT-4 〔mRNA（1.756±0.152） fold, total protein in cell （1.653±0.312） fold, protein in plasma membrane （2.041±0.258） fold〕 was increased in hypoxia-transfection group significantly (P＜0.05), but which was lower than that in normoxianontransfection group (P＜0.05). ④There was significantly positive relation between 3H-G intake and GLUT-4 protein expression in plasma membrane (r=0.415, P=0.001).Conclusion GLUT-4 may take part in glucose uptake of MSCs, and the capability of Akt gene to improve MSCs anti-hypoxia may be finished by its role in increasing the expression and translocation of GLUT-4.