ABSTRACT
OBJECTIVE@#To investigate the protective effect of serine hydroxymethyl transferase 2 (SHMT2) against hepatic ischemia-reperfusion injury in mice.@*METHODS@#Sixty C57BL/6 mice were divided equally into sham-operated group, saline adeno-associated virus group (AVV-GFP), and adeno-associated virus silencing group (AAV-SHMT2). The adeno-associated virus and normal saline were injected into the tail vein of the mice 2 weeks before establishment of a 70% ischemia-reperfusion model in the liver. qPCR, Western blotting, immunofluorescence and immunohistochemistry were used to detect the changes of AST/ALT concentration, SHMT2, JNK, NF-κB, caspase-3 and downstream inflammatory factors in the mice, and HE staining was used to observe the pathological damage of the liver tissue in each group; the cell apoptosis in the liver was detected using TUNEL assay.@*RESULTS@#The expression of SHMT2 increased with time after hepatic ischemia-reperfusion and reached the highest level at 24 h (the relative expression was 1.5, < 0.05). At 24 h after hepatic ischemia-reperfusion, the levels of AST/ALT in AAV-SHMT2 group (588/416 U/L) were significantly higher than those in the control group (416/345 U/L) and the empty vector group (387/321 U/L) ( < 0.05). Compared with those in the control group and the empty vector group, the level of SHMT2 was significantly decreased in AAV-SHMT2 group (with a relative expression of 0.24, < 0.05), the levels of p-JNK and p-p65 were significantly increased (relative expression of 0.80 and 0.97, respectively, < 0.05), and the levels TNF-α and IL-1β were consistently elevated (relative expression levels of 1.6 and 1.2, respectively, < 0.05). No significant differences were found in these parameters between the empty vector group and the control group (>0.05).@*CONCLUSIONS@#SHMT2 may alleviate liver cell apoptosis in mice with hepatic ischemia-reperfusion injury by inhibiting the activation of JNK pathway and excessive activation of NF-κB pathway to reduce hepatic damage.
Subject(s)
Animals , Mice , Apoptosis , Liver , Methyltransferases , Mice, Inbred C57BL , NF-kappa B , Reperfusion Injury , SerineABSTRACT
Objectives To evaluate the efficacy and safety of single-incision versus conventional laparoscopic cholecystectomy.Methods We searched electronic databases (PubMed,EMBASE,Cochrane Library,Chinese Biomedicine databases) from January 2000 to April 2012.Personal contact with experts in the field of laparoscopic cholecystectomy was performed to identify further potentially relevant clinical trials.Randomized controlled trials conducted on single-incision versus conventional laparoscopic cholecystectomy were analysed to compare conversion rates,blood loss,operation time,postoperative complications,wound satisfaction score,postoperative pain score and postoperative duration of hospitalization.Data were extracted by two reviewers independently.Statistical analysis was performed by using the RevMan 5.1 software.Results Twelve studies involving 915 patients met the inclusion criteria.When compared with conventional laparoscopic cholecystectomy (LC),the singleincision laparoscopic cholecystectomy (SILC) group showed no significant difference in conversion rate (OR=0.70,95％CI: 0.13～3.77,P=0.68),postoperative complications (OR=1.13,95％CI:0.72～1.78,P＝0.59) and postoperative pain scores (WMD＝-0.18,95％CI:-0.78～-0.43,P=0.57) . There was a significant increase in operative blood loss (WMD ＝ 1.43,95 ％ CI: 0.09 ～2.78,P＜0.05),increase in operative time (WMD=16.79,95％CI: 9.05～24.52,P＜0.01),but an increase in wound satisfaction score (WMD=1.28,95％CI..1.09～1.47,P＜0.01).The postoperative duration of hospitalization was significantly shorter (WMD =-0.30,95％ CI:-0.58 ～-0.02,P＜0.05).Conclusions Current evidence suggests that there is no significant difference in conversion rate or postoperative complications between SILC and LC.Although SILC requires a longer operative time and there is more blood loss when compared with LC,the SILC is superior in wound satisfaction score and in duration of hospitalization.
ABSTRACT
Objective To study the relationship between expression of G-protein-coupled bile acid receptor 1 (GPBAR1) in gallbladder mucosa and formation of lithogenic bile in patients with gallstones.Methods Gallbladder mucosa,gallbladder wall,bile and plasma were collected from 34 patients with gallstone (GS) and 15 individuals who were gallstone free (GSF).The gallbladder wall was stained with hematoxylin-eosin (HE) and immunohistochemistry to detect pathologic changes and expressions of GPBAR1,mucin 1 (MUC1) and mucin 5AC (MUC5AC).Reverse-transcription polymerase chain reaction (RT-PCR) was used to test mRNA expressions of GPBAR1,MUC1 and MUC5AC in the gallbladder mucosa.The contents of total cholesterol (TC),total bile acid (TBA),triglyceride (TG),low density lipoprotein (LDL) and high density lipoprotein (HDL) in plasma and cholesterol,TBA,phospholipid (PL) and mucin in the bile of gallbladder were measured.Results The gallbladder mucosa in all GS patients showed chronic inflammation on hematoxylin-eosin staining.The expressions of GPBAR1 and MUC5AC were more markedly increased in the GS group than in the GSFgroup (61.34±8.06 vs.43.05±7.83,P＜0.01; 52.11±9.62 vs.45.05±9.27,P＜0.05).The mRNA expressions of GPBAR1 and MUC5AC in the GS group were also more markedly increased than in the GSR group (0.87±0.07 vs.0.80±0.09,P＜0.05; 1.04±0.22 vs.0.8±0.17,P＜0.01).Serum cholesterol,as well as biliary cholesterol,cholesterol mol percentage,cholesterol saturation index and mucin in the GS group were more significantly higher than in the GSF group (5.07±1.64 vs.3.62±1.42,P＜0.01; 17.23±3.67 vs.12.47±2.31,P＜0.01; 7.47±0.65 vs.5.05±0.24,P＜0.01; 1.03±0.58 vs.0.69±0.38,P＜0.01; 92.02±20.89 vs.76.36±19.71,P＜0.05).Biliary total bile acids and bile acids mol percentage were lower in the GS group than in the GSF group (162.68±20.19 vs.180.21±26.05,P＜0.05; 71.28±1.84 vs. 73.29±0.96,P＜0.01). In the GS group,there were negative correlations between the mRNA expression of GPBAR1 and biliary TBA (γ=-0.341,P＜0.05).There were negative correlations in the GS group between the GPBAR1 expression and the level of biliary TBA (γ=- 0.403,P＜0.05),and between the GPBAR1 expression and the level of biliary total lipid (γ=-0.365,P＜0.05).Conclusions This study shows an increase in expression of GPBAR1 in gallbladder mucosa in patients with GS.It is suggested that GPBAR1 may accelerate formation of lithogenic bile by inducing re-absorption of bile acid.