A Meta-analysis Of The Effectiveness Of Moderate To Severe IUA Therapy And Study On The Injury Mechanism Of HDMSCs Under Oxidative Stress

Objectives:1.To assess the effectiveness of balloon and intrauterine device?IUD?after transcervical resection of adhesion?TCRA?in moderate or severe intrauterine adhesions,and provide an evidence-based basis for the appropriate treatment after TCRA.2.The oxidative stress model of human decidual mesenchymal stem cells?hDMSCs?was established.The changes of cell morphology,cellular reactive oxygen species,mitochondrial membrane potential and apoptosis-related proteins were observed to understand under oxidative stress conditions whether reactive oxygen species ROS can induce h DMSCs apoptosis by mediating mitochondrial levels.METHODS:1.Published literatures were searched on the treatment of moderate to severe intrauterine adhesions using balloon and IUD after TCRA.Papers were searched in databases such as PubMed,CENTRAL,SCIE,Embase,VIP,CNKI and Wanfang database for the time Published studies in Chinese/English from January 2010 to September 2017,including inclusion and exclusion criteria,rigorous screening of the literature,all datas using Revman 5.2 statistical software and forest and funnel chart analysis.2.Oxidative stress model of hDMSCs in vitro was established,using H₂O₂ to simulate intrauterine adhesions environment.P3 generation of hDMSCs was treated with 0,10,40,160,320,320 mmol/L hydrogen peroxide solution respectively.After 6 hours,the morphological change and antioxidant capacity were observed,and change in mitochondrial membrane potential and relative changes of apoptosis related proteins.RESULTS:1.The final inclusion of the standard literature had 15 articles.A total of 1389 cases underwent moderate to severe adhesion were treated with balloon and IUD after TCRA,of which 698placed balloons to prevent postoperative adhesions and 691 placed IUDs to prevent adhesions.Meta-analysis showed that:?1?Fifteen studies comparing postoperative adhesions,the incidence of re-adhesions in the IUD group was significantly higher than that in the balloon group?Z=5.83,OR 0.46,95%CI 0.36-0.60,P<0.00001?.?2?The postoperative pregnancy rates of the two groups were compared in three studies.There was no significant difference in postoperative pregnancy rates between the IUD group and the balloon group?Z=1.34,OR 1.56,95%CI0.82-2.96,P=0.18?.?3?Over 10 articles reported the rate of postoperative menstrual improvement.Meta-analysis showed that the improvement rate of menstruation in balloon group after TCRA was higher than that in IUD group?Z=6.83,OR 3.23,95%CI 2.31⁴.53,P<0.00001?2.Cell morphological changes:After treated with 10?M H₂O₂ for 6 hours,the cells maintained their original fusiform appearance,and the cells were slightly swollen with a slight decrease in density.With the increase of H₂O₂ concentration,the cells gradually shrunk,the intercellular junctions decreased,and the density reduced,causing visible apoptotic cells and cell fragmentation.3.The changes of oxidant and antioxidant capacity:The activity of superoxide dismutase?SOD?decreased with the increase of hydrogen peroxide concentration,and there was a negative correlation between them?r_s=-0.904,P=0.035?.Compared with the control group,the SOD activity of each concentration group was statistically significant?P<0.05?.The concentration of glutathione decreased as the hydrogen peroxide concentration increased,and there was a negative correlation between them?r_s=-0.975,P=0.05?.The concentration of glutathione in each concentration group was compared with the control group.The difference was statistically significant?P<0.05?.The malondialdehyde?MDA?concentration increased with the increase of hydrogen peroxide concentration.There was a positive correlation between them?r_s=0.975,P=0.005?.The concentration of MDA in each concentration group was compared with the control group.The difference was statistically significant?P<0.05?.The microplate reader showed that the average fluorescence of intracellular ROS increased with the increase of H₂O₂ concentration.Compared with the control group,the mean fluorescence of ROS increased in each concentration group,and the difference was statistically significant?P=0.000?.4.Changes in mitochondrial membrane potential:There was no significant difference in the ratio of red-green fluorescence between the 10?M group and the control group?P<0.05?;the mitochondrial membrane potential was decreased in the remaining four concentration groups compared with the blank group.All were statistically significant?P=0.000?.Except for 80?M group and 160?M group,there was no statistically significant difference?P>0.05?.There was significant difference between different concentration groups?P<0.05?.5.The relative expression of PARP-1 in each group was 320?M?1.004?,160?M?0.959?,80?M?0.740?,40?M?0.406?,10?M?0.211?,Control group?0.150?.Compared with the control group,there was no significant difference in the 10?M group?P=0.154?,and the other 4 groups were significant differences.There was no significant difference between the five experimental groups except the 320?M group and the 160?M group Difference?P=0.282?,the rest of the experimental groups were significantly different.The relative expression of Caspase-3 in each group was 320?M?0.973?,160?M?0.730?,80?M?0.620?,40?M?0.096?,10?M?0.092??0.003?.There was significant difference between each experimental groups and the control group.There was significant difference between the five experimental groups except for 10?M group and 40?M group?P=0.895?.Conclusion1.Compared with IUD,balloon placement after TCRA can significantly reduce the rate of re-adhesion and the incidence of menstrual decline,but no significant improvement in postoperative pregnancy rate.2.In the H₂O₂-simulated uterine cavity adhesion environment,ROS-mediated mitochondrial membrane potential is involved in oxidative stress-induced apoptosis of h DMSCs,and ROS is expected to become a therapeutic target for optimizing the clinical efficacy of hDMSCs.