ABSTRACT
Purpose@#Multiple pathways are involved in inducing liver fibrosis, which can damage the integrity of liver. Among them, miR-125b has been found to exert an activating action on hepatic stellate cells. Endoplasmic reticulum stress and autophagy lead to liver disorders. Here, we evaluated the therapeutic influence of miR-125b on the endoplasmic reticulum function in injured livers submitted to bile duct ligation. @*Materials and Methods@#For inducing injury, bile duct ligation was done on miR-125b transgenic rats (miR-125b-Tg) in wild type rats. The rat T-6 cells received transfection of miR-125b mimic and Tunicamycin. Protein expressions were observed by western blot analysis. @*Results@#Compared to wild type rats, liver-injured rats showed significant impairment of liver function as assessed by the total bilirubin levels. The miR-125b-Tg rats showed decrease in activity of aspartate transaminase and alanine transaminase. Liver tissues of miR-125b-Tg rats showed weaker fibrotic matrix formation. Upregulation of miR-125b decreased the bile duct ligation-mediated hepatic disturbances for the expressions of endoplasmic reticulum kinase, inositol-requiring kinase 1alpha, sXBP1, CHOP, LC3, p62, ULK, and caspase-3/-8/-9. T-6 cells transfected with miR-125b mimic and treated with Tunicamycin caused decrease in levels of cleaved caspase-3, sXBP1, CHOP, and LC3. The miR-125b signaling showed protective effect on the liver tissues subjected to injury and fibrosis histopathology. @*Conclusion@#This study demonstrates a novel insight into the miR125b-mediated stabilization of endoplasmic reticulum integrity, which slows the progression of injury-induced hepatic deterioration.
ABSTRACT
Purpose@#Multiple pathways are involved in inducing liver fibrosis, which can damage the integrity of liver. Among them, miR-125b has been found to exert an activating action on hepatic stellate cells. Endoplasmic reticulum stress and autophagy lead to liver disorders. Here, we evaluated the therapeutic influence of miR-125b on the endoplasmic reticulum function in injured livers submitted to bile duct ligation. @*Materials and Methods@#For inducing injury, bile duct ligation was done on miR-125b transgenic rats (miR-125b-Tg) in wild type rats. The rat T-6 cells received transfection of miR-125b mimic and Tunicamycin. Protein expressions were observed by western blot analysis. @*Results@#Compared to wild type rats, liver-injured rats showed significant impairment of liver function as assessed by the total bilirubin levels. The miR-125b-Tg rats showed decrease in activity of aspartate transaminase and alanine transaminase. Liver tissues of miR-125b-Tg rats showed weaker fibrotic matrix formation. Upregulation of miR-125b decreased the bile duct ligation-mediated hepatic disturbances for the expressions of endoplasmic reticulum kinase, inositol-requiring kinase 1alpha, sXBP1, CHOP, LC3, p62, ULK, and caspase-3/-8/-9. T-6 cells transfected with miR-125b mimic and treated with Tunicamycin caused decrease in levels of cleaved caspase-3, sXBP1, CHOP, and LC3. The miR-125b signaling showed protective effect on the liver tissues subjected to injury and fibrosis histopathology. @*Conclusion@#This study demonstrates a novel insight into the miR125b-mediated stabilization of endoplasmic reticulum integrity, which slows the progression of injury-induced hepatic deterioration.
ABSTRACT
Objective To investigate the effect of reinfusion of drained bile and pancreatic juice on the outcome of pancreaticoduodenectomy (PD).Methods The clinical data of 51 patients who received PD at the Affiliated Hospital of Binzhou Medical College from June 2005 to March 2009 were retrospectively analyzed.Nineteen patients received external drainage of bile and pancreatic juice ( ED group) and the other 32 patients received external drainage and intraintestinal administration of autologous bile and pancreatic juice (ID group).The daily volume of output of bile and pancreatic juice,intraoperative condition,tolerance of enteral nutrition,liver function and nutritional parameters of the 2 groups were detected.All data were analyzed by using chi-square test,Fisher exact test,independent t test,Mann-Whitney U test and one-way analysis of variance.Results The pulmonary infection rate of ID group was 3％ (1/32) after operation,which was significantly lower than 26％ (5/19) of the ED group (P ＜ 0.05).The output of pancreatic juice in the ID group was significantly lower than that in the ED group since postoperative day 4 ( t =7.143,9.244,8.808,7.915,6.461,14.097,15.038,P ＜ 0.05 ).There was no significant difference in the daily output of bile between the 2 groups.The incidence of diarrhea in the ID group was 9％ (3/32) after nutritional support,which was significantly lower than 37％ (7/19) of ED group (P＜0.05).The duration of achieving targeted enteral feeding in the ID was 3 days,which was significantly shorter than 4 days of the ED group ( U =145.000,P ＜ 0.05 ).The levels of total bilirubin ( TBil),direct bilirubin (DBil) and indirect bilirubin (IBil) were (261 ± 108 ),( 132 + 55 ) and ( 129 + 55 ) μmol/L in the ID group,and (239 ±92),( 12A ±46) and ( 116 ±46) μmol/L in the ED group before operation.The levels of TBil,DBil and IBil were (39 ± 19),(20 ± 10) and ( 19 +9) μmol/L in the ID group,and (55 ±22),(29 ± 12) and (26 ±11 ) μmol/L in the ED group at 12 days after nutritional support.There were significant differences in the decrease of TBil,DBil and IBil between the 2 groups ( t =7.324,8.437,5.827,P ＜ 0.05 ).The levels of serum prealbumin,retinol binding protein and transferrin were (0.261 ± 0.021 ) g/L,(34.3 ± 2.8 ) mg/L,(3.08 + 0.26 ) g/L in the ID group,and (0.263 ±0.021)g/L,(33.8 +3.5)mg/L and (3.10 +0.27)g/L in the ED group before operation.The levels of serum prealbumin,retinol binding protein and transferrin decreased significantly after operation,and then got increased 3 days after nutritional support.The levels of serum albumin,retinol binding protein and transferrin were (0.238 ±0.025)g/L,(30.7 ±2.0)mg/L,(2.78 ±0.19)g/L in the ID group,and (0.222 +0.025)g/L,(29.3 ±2.1)mg/L and (2.63 +0.21)g/L in the ED group at 12 days after nutritional support.The levels of serum albumin,retinol binding protein and transferrin in the ID group were significantly higher than those in the ED group (t=4.615,6.097,4.913,P＜0.05).Conclusion Reinfusion of external drained bile and pancreatic juice after PD could enhance the tolerance of patients in early enteral nutrition,reduce incidence of pneumonia,promote decrease of serum bilirubin and improve the nutritional status.
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Objective To explore the possible role and mechanism of the Kupffer cells (KCs) in liver allo-geneic transplantation at the early stage. Methods In vitro cell contact coculture system was established. Culture supernatants were collected respectively on the 1st, 2nd, 4th, 6th d after cocul-ture and the KCs and PBMCs were harvested on the 6th day after culture. The expression of HLA-G on the membrane of the KCs and PBMCs was detected with immunochemistry. Nitrate reduction test was used to determine the concentration of nitric oxide. IFN-γ, IL-10, TGF-β1 cytokine levels in the supernatants were also measured with ELISA. The proliferation of lymphocytes was evaluated with MTT. Results six days later, no HLA-G molecules were detected on the membrane of the KCs and PBMCs. In the experimental group containing KCs, the levels of NO, IL-10 and TGF-β1 was signifi-cantly increased(P<0. 05), while the levels of IFN-γ was relatively lower(P<0. 05) as compared to the experimental group without KCs. No IL-10 and IFN-γ were detected in the control group, and on-ly few NO and TGF-β1 was found in the control group with KCs. MTT test showed that the value of optical density was lower in the experimental group with KCs than that in any other group(P<0. 05).Conclusion No HLA-G is expressed on the membrane of KCs and PBMCs after contact coculture.KCs may participate in regulating production of NO and Th2/Th3-like cytokines and suppressing the proliferation of lymphocytes, through which KCs probably take part in inducing immunotolerance of liver transplantation in early stage.