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Objective To investigate the role of human umbilical cord mesenchymal stem cell-derived extracellular vesicle (hUC-MSC-EV) in the regeneration of fibrotic liver. Methods C57BL/6 mice were randomly divided into the 70% normal liver resection group (Oil+PHx group), 70% liver fibrosis resection group (CCl4+PHx group) and 70% liver fibrosis resection+mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment group (CCl4+PHx+MSC-EV group), with 8 mice in each group. LX-2 cell lines were assigned into the phosphate buffer solution (PBS) group, transforming growth factor (TGF)-β group and TGF-β+MSC-EV group. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in mice after partial liver resection were detected in each group. The expression levels of liver fibrosis and proliferation-related parameters were analyzed in each group. The messenger RNA (mRNA) expression levels of epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in LX-2 cells were detected in each group, and their effects on HGF expression in mouse liver were observed. Results Compared with the Oil+PHx group, the serum levels of AST, ALT and LDH were up-regulated, and the degree of fibrosis was more severe, the positive area of Sirius red and α-smooth muscle actin (α-SMA) staining was larger, and the expression level of α-SMA protein was up-regulated in the CCl4+PHx group. Compared with the CCl4+PHx group, the serum levels of AST, ALT and LDH were decreased, the degree of fibrosis was slighter, the positive area of Sirius red and α-SMA staining was decreased, and the expression level of α-SMA protein was down-regulated in the CCl4+PHx+MSC-EV group, and the differences were statistically significant (all P < 0.05). Compared with the Oil+PHx group, the protein expression levels of Ki67 and proliferating cell nuclear antigen (PCNA) were lower in the CCl4+PHx group. Compared with the CCl4+PHx group, the protein expression levels of Ki67 and PCNA were increased in the CCl4+PHx+MSC-EV group, and the differences were statistically significant (all P < 0.05). Compared with the PBS group, the expression level of CollagenⅠ mRNA in LX-2 cells was increased, the expression level of α-SMA protein was up-regulated and the expression level of HGF protein was decreased in the TGF-β group. Compared with the TGF-β group, the expression level of CollagenⅠ mRNA in LX-2 cells was decreased, the expression levels of HGF mRNA and protein were increased, and the expression level of α-SMA protein was decreased in the TGF-β+MSC-EV group, the differences were statistically significant (all P < 0.05). The expression level of HGF protein in the CCl4+PHx group was lower than that in the Oil+PHx group, whereas the difference was not statistically significant (P > 0.05). The expression level of HGF protein in the CCl4+PHx+MSC-EV group was higher than that in the CCl4+PHx group, and the difference was statistically significant (P < 0.05). Conclusions The regenerative capacity of fibrotic liver is weaker than that of normal liver. hUC-MSC-EV may alleviate liver fibrosis and improve liver regeneration by promoting HGF secretion from actived hepatic stellate cells and effectively enhancing the regenerative capacity of fibrotic liver.
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【Objective】 To investigate the effects of tranexamic acid(TXA) on intraoperative blood transfusion(volume) and postoperative coagulation function in patients with partial hepatectomy for hepatic hydatid disease in high altitude area(altitude ≥2 500 m). 【Methods】 Forty-four patients [(39.09±14.70) years old, 19 males and 25 females] underwent elective partial hepatectomy for hydatid after general anesthesia from October 2018 to December 2019 in the Department of Hydatid of Qinghai Provincial People's Hospital, with ASA gradeⅠ~Ⅲ, Child Pugh grade A~B, and normal preoperative coagulation function. They were randomly divided into TXA injection group, who received intravenous injection of TXA 10 mg/(kg·person)(30 min before surgery), and control group, given a placebo needed the equal amounts of injected 0.9% sodium chloride(30 min before surgery). 3 mL of arterial blood was extracted from each patient before intravenous injection and at the end of operation for TEG detection. The intraoperative blood loss and transfusion volume as well as Plt, Hb and TEG parameters before and after surgery were compared between the two groups, and statistical analysis was performed with SPSS22.0 statistical software. 【Results】 The volume of intraoperative blood loss(mL) in TXA group and control group was 300(200, 1 000) vs 1 400(1 000, 2 100), respectively; the units of plasma transfusion(mL) 0(0, 0) vs 380(0, 575); the units of RBC suspension transfusion(mL) 0(0, 400) vs 1 200(800, 600). Preoperative TEG parameters of two groups were similar to each other(P>0.05). The postoperative R, K and Angle(°) of two groups was 8.32±2.24 vs 10.78±2.67, 2.80(2.10, 3.30) vs 3.70(3.20, 4.80) and 54.76±9.48 vs 43.70±9.02, respectively(P<0.05). 【Conclusion】 TXA can significantly improve coagulation functions, as well as effectively reduce intraoperative blood loss and intraoperative blood transfusion in patients with partial hepatic resection of hydatid hepatica in high altitude area.
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Objective:To study the optimal surgical strategy for patients with hepatocellular carcinoma (HCC) presenting with spontaneous rupture and hemorrhage.Methods:The electronic databases of PubMed, Web of Science, Embase, and Cochrane Library were searched, and studies reporting on survival outcomes comparing emergency resection (ER) and transarterial embolization followed by hepatectomy (SH) were included by using predetermined inclusion and exclusion criteria. The perioperative and survival data were compared using the Review Manager 5.3 software.Results:Eight retrospective studies were included. The total sample size was 556, with 285 (51.3%) in the ER group and 271 (48.7%) in the SH group. Perioperative blood loss ( WMD=683.61, 95% CI: 283.36-1 083.86, P=0.0 008) and blood transfusion volume ( WMD=453.43, 95% CI: 250.27-656.58, P<0.0 001) in the SH group were significantly less than those in the ER group. There were no significant differences in operative time, incidences of complications, mortality and recurrence rates of tumors between the two groups (all P>0.05). The 1-, 2-, 3-year overall survival and 1-, 2-, 3-, 5-year disease-free survival of the ER group were not significantly different from those of the SH group (all P>0.05). The 5-year overall survival rate of the ER group was significantly lower than that of the SH group ( HR=1.52; 95% CI: 1.14-2.03, P=0.005). Conclusions:There was no significant difference in short-term outcomes in treatment of ruptured HCC, SH was superior to ER in long-term survival outcomes.
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Objective • To explore the effect of inhibiting transforming growth factor β (TGF-β) signaling pathway on the stem cell-mediated liver regeneration in mice after partial hepatectomy (PH). Methods • Eighteen C57BL/6 male mice were selected to establish the model of hepatectomy. mRNA and protein levels of the signal molecules in TGF-β pathway, as well as stem cell markers α-fetoprotein (AFP) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in the liver tissues were detected before (PH0) and on the 1st (PH1), 3rd (PH3) and 7th (PH7) day after operation. Then, additional 32 mice were assigned into inhibitor group [PH+SB-431542, 10 mg/(kg•d)] and control group (PH+normal saline). The mice were sacrificed on the 1st (PH1) and 3rd (PH3) day after operation and liver remnants were obtained. Realtime-PCR, Western blotting, and immunofluorescence staining were used to detect the expressing variation of TGF-β signaling pathway, AFP and LGR5. Results • The mRNA and protein expression of TGF-β1, phosphorylated SMAD2 (p-SMAD2) protein, Afp mRNA, the number of AFP immune-positive cells and Lgr5 mRNA were upregulated significantly after PH, peaked at PH3 (P<0.05) and recovered to pre-operative level at PH7. Compared with control group, the above indices were all obviously inhibited in inhibitor group at PH3 (P<0.05). Conclusion • TGF-β signaling pathway may regulate the stem cell-mediated liver regeneration in mice after PH.
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Objective To contrastively study the effects of NERC-300 high frequency welding device and ultrasonic scalpel in rat partial hepatectomy.Methods Forty-eight rats were divided into the experimental group and control group(n=24).The experimental group applied NERC-300 high frequency welding instrument for conducting partial hepatectomy,while the control group used ultrasonic scalpel.The survival rate,operation time,bleeding volume,working temperature,extent of hepatic thermal damage and change of liver function on 1,3,7 d were compared between the two groups.Results The liver function recovery on 3 d in the experimental group was superior to the control group (P＜0.05).The intra-operative working temperature in the experimental group was lower than that in the control group(P＜0.05).The thermal damage range in the experimental group was lower than that in the control group(P＜0.05).The survival rate,operation time,bleeding volume and liver function change on 1,7 d had no statistical differences between the two groups(P＞0.05).Conclusion NERC-300 high frequency welding device is safe and effective for partial hepatectomy in rat.
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Objective To explore the effects of curdione on cognitive function and expression of inflammatory factors in the hippocampus after partial hepatectomy in aged mice.Methods The animals were divided into control group, sham group, operation group, and high-, medium-and low-dose curdione groups.The model of partial hepatectomy in aged mice was established according to the method reported in literature.The levels of SOD, MDA, CAT and GSH-Px in the hippocampus were detected by enzyme-linked immunosorbent assay (ELISA), while the expressions of NF-κB, IL-1β, IL-6 and TNF-α were measured by Western blot.Results The escape latency was significantly increased (P<0.01), and the number of platform-site crossovers was significantly decreased in operation group (P<0.05).Compared with those in operation group, curdione significantly decreased escape latency and increased platform-site crossovers (P<0.05, P<0.05).The levels of SOD, CAT and GSH-Px in the hippocampus were significantly decreased (P<0.05) and the content of MDA was significantly increased after partial hepatectomy (P<0.01), and these were reversed by curdione (P<0.05, P<0.05, respectively).The expressions of NF-κB, IL-1β, IL-6 and TNF-α protein were significantly inhibited by curdione (P<0.05).Conclusion Curdione can significantly improve cognitive dysfunction after partial hepatectomy in aged mice and the mechanism may be related to its inhibition of oxidative stress, inhibition of NF-κB activation and reduction of inflammatory cytokines IL-1β, IL-6 and TNF-α in the hippocampus.
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Objective To investigate the effects of neurolytic celiac plexus block(NCPB) on stress response during the early stage of partial hepatectomy(PH) postoperation in rats.Methods Thirty healthy SPF-grade male Sprague-Dawley rats were randomly divided into control group and NCPB group,and then were constructed the 70％ PH model.NCPB group received NCPB with 0.5 ％ lidocaine before closing abdominal,and control group received the same procedures,but 0.9％ physiological saline was injected instead of 0.5 ％ lidocaine.The serum concentration of CRP,GC,ACTH,NA and AD,and the levels of serum TNF-α and IL-1β were determined at 6 hours,12 hours and 24 hours after PH.The western blot assay was performed to examine the expression of GR in the peripheral blood mononuclear cells (PBMCs).Results The obvious stress response was produced within 24 hours after PH in rats,postoperative serum CRP,GC,ACTH,NA and AD concentrations increased in the different extent,but the NCPB group were significantly lower than those in the control group in the corresponding time point (P ＜0.01 or P ＜0.05).The expression levels of GR in PBMCs in the control group were significantly decreased after PH,and markedly lower than those in the NCPB group in the corresponding time point(P ＜ 0.01).The serum TNF-o and IL-1β levels were gradually increased in the control group and NCPB group within 24 hours after PH.But at the respective time points,the levels in the NCPB group were significantly lower than those in control group(P ＜ 0.01 or P ＜ 0.05).Conclusion Intraoperation NCPB can effectively inhibit postoperative stress response at the early stage after PH,and thereby help to reduce the degree of systemic inflammatory response.
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Objective To study the promoting effects and mechanisms of interleukin-22 on liver regeneration in GCl4-induced liver fibrosis mice after partial hepatectomy.Methods One hundred and fortyfour C57/BL6 mice were randomly divided into four groups:PHX group,CCl4 group,CCl4 + PHX group,and CCl4 + IL22 + PHX group.The blood samples were taken to measure serum ALT and AST levels.ALT /AST was calculated to observe the liver injury at 3 h,6 h,12 h,24 h,48 h and 72 h after hepatectomy.The liver tissue specimens were collected at each time point after hepatectomy.We measured the hepatic lobe to calculate the liver weight ratio and conducted pathological examinations to observe the degree of fibrosis and pathological changes at each time point.The positive expression of proliferating cell nuclear antigen (PCNA) in liver tissue was tested by immunohistochemistry.The level of CyclinD1 and STAT3 (Signal transducer and activator of transcription 3) signaling pathway was detected by Western blot.Results (1) Compared with CCl4 + PHX group,the ALT/AST ratio of CCl4 + IL22 + PHX group was significantly higher at 24 h,48 h and 72 h,and the level of ALB of CCl4 + IL22 + PHX group was obviously increased at 48 h and 72 h (P ＜ 0.05).(2) The liver regeneration was significantly increased in CCl4 + IL22 + PHX group.Compared with CCl4 + PHX group (2.08 ± 0.16,2.77 ± 0.07,2.97 ± 0.14),the liver weight ratio of CCl4 + IL22 + PHX group(2.34 ± 0.07,3.23 ± 0.09,3.55 ± 0.09) dramatically increased at 24 h,48 h and 72 h.Moreover,the pathological sections displayed that the disease was alleviated (P ＜ 0.05).(3) Immunohistochemical assay and western blot revealed that compared with other three groups,the level of PCNA,STAT3 and Cyclin D1 was significantly lower in the CCl4 + PHX group.However,the level of PCNA,STAT3 and Cyclin D1 apparently increased in CCl4 + IL22 + PHX group at 24 h,48 h and 72 h (P ＜ 0.05).Conclusion Interleukin-22 may significantly promote liver regeneration and reduce liver pathological injury in liver fibrosis mice induced by administration of CCl4 after hepatectomy,which plays a positive role in the recovery of liver function.
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ABSTRACT Quercetin has potent antioxidant action and a hepatoprotective role. The aim of this study was to evaluate the hepatoprotective action of quercetin pretreatment in paracetamol-induced liver damage (PILD) and structural injury resulting from partial hepatectomy (PH). In the first model, Wistar rats received oral quercetin (50mg/kg/day) during 8 days. On the 8th day, 3g/kg paracetamol were added. In the second model, the same quercetin dose was given during 7 days and rats were submitted to PH on the 8th day. Blood samples were obtained for determination of enzyme levels. Liver, heart, kidney and lung tissue were also collected for assessment of quercetin biodistribution and/or histological analyses. The results obtained after PILD were more pronounced at 24 hours, as reflected by the reduction of serum ALT levels and by the lower concentration of quercetin in liver at this time point. Quercetin also had a protective effect in groups submitted to PH, as shown by decreased ALT levels after 18 hours, and of AST levels after 18 and 36h. The reduction in serum AST and ALT levels suggest that treatment with quercetin is useful as a preoperative pharmacologic measure and for prevention of liver damage caused by drugs.
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<p>Liver metastases from colorectal carcinoma commonly form nodular lesions in the liverparenchyma. We report a case of liver metastasis from rectal adenocarcinoma that extendedpredominantly into the bile duct. A 62-year-old Japanese man underwent low anteriorresection for rectal adenocarcinoma 9 years ago. Approximately 3 years later, he underwentradiofrequency ablation therapy for a metastatic liver tumor. Nine years after surgery, atumor in liver segment III exhibiting intrabiliary extension was discovered; it wasunclear if this was a metastatic liver tumor or intrahepatic cholangiocarcinoma.Accordingly, we performed a left hepatectomy with lymph node dissection. The tumor wasnegative for cytokeratins 7 and 20, and was histologically similar to the primary rectaladenocarcinoma; it was diagnosed as rectal carcinoma metastasis. The patient has survivedfor 3 years after the hepatic surgery, for 9 years after radiofrequency ablation therapy,and for 12 years after the primary surgery. This case shows that liver metastasis fromcolorectal carcinoma can present as a predominantly intrabiliary growth that mimicsintrahepatic cholangiocarcinoma on imaging. Moreover, our case provides evidence for thesuperiority of anatomical hepatectomy over partial hepatectomy for metastatic liver tumorswith intrabiliary growth arising from rectal adenocarcinomas.</p>
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Objective To explore the predictive value of spleen?liver volume ratio( SLVR) on the prog?nosis of partial hepatectomy in patients with hepatocellular carcinoma. Methods Clinical data of 86 cases of hepatocellular carcinoma underwent hepatectomy who were treated in the Traditional Chinese Medicine Hospital of Guangzhou from January 2009 to December 2014 were analyzed retrospectively. According to the preoperative spleen?liver volume ratio,these patients were divided into 2 groups:those with SLVR5 cm,the number of tumor>3,por?tal vein or hepatic vein tumor thrombus,preoperative AFP?L3%≥10%,the rate of Invasion of blood vessels and the percentage of positive margins of high SLVR group all significantly lower than that of low SLVR group (25. 0%(11/44) vs. 59. 5%(25/42),22. 7%(10/44) vs. 54. 8%(23/42),9. 1%(4/44) vs. 26. 2%(11/42),38. 6%(17/44) vs. 78. 6%(33/42),18. 2%(8/44) vs. 38. 1%(16/42),2. 3%(1/44) vs. 14. 3%(6/42);χ2=20. 645,16. 180,24. 728,4. 819,18. 402,20. 105;P5 cm,SLVR ≥0. 8,AFP?L3≥10%,and portal vein or hepatic vein tumor thrombus were independent predictors of poor disease?free survival after hepatectomy for hepatocellular carcinoma( Or=6. 141, 3. 753,6. 968,7. 763;P<0. 05). Conclusion Preoperative SLVR ≥0. 8 is an independent adverse predictor of poor disease?free survival,can preliminarily predict the prognosis of patients with hepatocellular carcinoma.
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Objective To investigate the effect of dexmedetomidine (Dex)on long-term cogni-tive function after partial hepatectomy (PH)in mice.Methods Forty adult male C57BL/6J mice were randomly divided into control group (group C),group PH,normal saline group (group NS)and group Dex,10 mice per each group.At 2 days after PH,the mice of group C and group PH under-went Morris water maze test,four times per day and a total of 4 days.The mice were euthanized and hippocampi tissue was immediately excised for determination of wet hippocampi weight to dry hipp-ocampi weight (W/D)and total hippocampi water content (TWC).The expression levels of cycteinyl aspirate-specific protease 12 (caspase-12)mRNA and protein of hippocampi tissue were detected re-spectively by reverse transcription-polymerase chain reaction (RT-PCR)and Western blot.Apoptosis index (AI)of hippocampi tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL)assay.After the mice regained consciousness after operation,animals re-ceived intraperitoneally Dex at a dose of 25 μg·kg-1 ·d-1 for 30 consecutive days in group Dex.Ani-mals of group NS were given intraperitoneally with the same volume of normal saline.After treatment for 30 consecutive days,the mice of group Dex and group NS underwent Morris water maze test,four times per day and a total of 4 days.The mice were euthanized and hippocampi tissue was immediately excised for determination of W/D and TWC.The expression levels of caspase-12 mRNA and protein of hippocampi tissue were detected respectively by RT-PCR and Western blot.AI of hippocampi tissue was determined by TUNEL assay.Results Compared with the first day,the escape latency at the third day,the fourth day and swimming distance were shortened in groups C,NS and Dex (P <0.05);Compared with group C,the escape latency at the third day,the fourth day and swimming distance were prolonged (P < 0.05 ), W/D,TWC and AI were higher (P < 0.05 ), and the expression levels of caspase-12 mRNA and protein of hippocampi tissue were significantly higher (P<0.05)in group PH.Compared with group NS,the escape latency at the third day,the fourth day and swimming distance were shortened (P <0.05),W/D,TWC and AI were lower (P <0.05)and the expression levels of caspase-12 mRNA and protein of hippocampi tissue were significantly lower (P <0.05)in group Dex.Conclusion The treatment of Dex could improve the long-term cognitive function after PH in mice,and the mechanism may be to lighten apoptosis mediated by caspase-12 in hippocampi tissue.
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Non-coding RNAs mainly include microRNAs and long non-coding RNAs (LncRNAs),which work as a kind of RNA to regulate the expression of gene at the levels of transcription,post-transcription and epigenetics.Recent studies have shown that many non-coding RNAs are dysregulated during liver regeneration after partial hepatectomy.This review summarized the biological characteristics and regulatory mechanisms of non-coding RNAs in liver regeneration after partial hepatectomy.
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OBJECTIVE:To explore the protective effect of L-ornithine-L-aspartate on ischemia-reperfusion injury after partial hepatectomy. METHODS:104 patients underwent partial hepatectomy(vessel occlusion in portal fissure)were randomly divided in-to control group(53 cases)and trial group(51 cases). Control group was given routine liver-protective drugs,and trial group was additionally given L-ornithine-L-aspartate 10 g added into 5%Glucose injection 250 ml intravenously before surgery,for 7 consecu-tive days. The fasting peripheral venous blood was collected in 2 groups on first day before surgery and first,forth and sixth day af-ter surgery to detect liver function;the changes of main aminopherase index(ALT and AST)were compared between 2 groups at different portal fissure vessel occlusion time after surgery. RESULTS:There was no statistical significance in the difference of liver resection range,blood loss,first porta hepatis vessel occlusion time and anesthesia time in both groups during operation (P>0.05). Compared to before surgery,liver function indexes raised to different extent in 2 groups after surgery,with statistical signifi-cance(P0.05). Among those patients under-went porta hepatis vessel occlusion with Pringle method and with occlude occlusion time ≥15 min,the AST and ALT level of con-trol group was higher than those of trial group after surgery,but albumin level was below trial group,with statistical significance (P<0.05). CONCLUSIONS:L-ornithine-L-aspartate could improve liver function fast and effectively for partial hepatectomy pa-tients,especially for the patients underwent porta hepatic vessel occlusion with Pringle method for a long time(obvious ischemia-re-perfusion injury).
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Fatty liver disease is a kind disease characterized by liver parenchyma cell degeneration caused by a variety of metabolic abnormalities.Fatty liver disease could be considered as a risk factor for partial hepatectomy,because it can not only increase intraoperative and postoperative morbidity and mortality,but also reduce the survival rate of liver transplant recipients.Therefore,this study focuses on the impact of fatty liver disease on liver regeneration after partial hepatectomy,which could guide the clinical strategy for the implementation of liver resection.This paper overviews the recent progress on the impact of fatty liver disease on liver regeneration after partial hepatectomy and the related mechanism.
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Objective To investigate the differential expression of hepatocyte growth factor activator (HGFA) and its inhibitors (HAI-1,HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy,and to explore the causes of the delayed liver regeneration after partial hepatectomy in cirrhotic rat model.Methods We used 40％ CCl4 subcutaneous injection to establish the cirrhotic rat model,and then performed 70％ liver resection for the experimental group together with no operation for the healthy rats as control group.Rats in each group after 3 hours,6 hours,12 hours,24 hours and 48 hours were randomly sacrificed and specimens were collected.The serum HGFA was detected by enzyme-linked immunosorbent assay (ELISA),and we used RT-PCR to detect the mRNA expressions of HAI-1 and HAI-2 in splenic tissue.Results The serum HGFA level in cirrhotic rats at each time point was all significantly lower than that in the control group (P ＜0.05).The expression of HAI-1 mRNA in cirrhotic rats was sustained at a higher level than that in the control group (P ＜ 0.05),but there was no significant difference on the HAI-2 mRNA expression between the two groups (P ＞ 0.05).Conclusions The synthesis of HGFA during the liver regeneration after partial hepatectomy in cirrhosis rats is lower compared with healthy rats,which may lead to the insufficient activation of HGF precursor,eventually causing the slow liver regeneration.HAI-2 may not be involved in the healing process of liver.
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Objective To investigate risk factors of infections in hepatic cancer patients after partial hepatectomy so as to provide theo-retical basis for the prevation of infections after the hepatecomy. Methods A total of 210 patients who underwent partial hepatectomy from December 2007 to December 2012 were divided into the infection group and the non-infection group,and they were retrospectively reviewed. Multivariate analysis was performed with logistic regression test. Results Totally 30 patients were infected after operation,and the incidence of infection was 14. 3%. There were singinficant difference between age,operation time,blood loss,blood transfusion and cirrhosis in the two groups(P<0. 05). Multivariate logistic regression analysis showed that the age,operation time,blood loss,blood transfusion and cirrhosis were significant risk factors for the infections after partial hepatecomy. Conclusion Aged over 60 years,operation time more than 5 hours, blood loss more than 3 000 mL,blood transfusion and cirrhosis were the key risk factors for the infections after partial hepatecomy.
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Objective To investigate the effect of neurolytic celiac plexus block (NCPB) on the inflammatory reaction of the remaining liver tissue and liver function after partial hepatectomy (PH) in rats.Methods Thirty male Sprague-Dawley rats of SPF were constructed as a PH model with deligation and ablation operated on their left and middle lobes,respectively.Then,they were randomly divided into two groups:NCPB group and control group.Twelve hours after the surgery,0.5％ lidocaine was given in the NCPB group once a day,while 0.9％ saline was given in the control group.Determination of liver function,generation of the remaining liver,and deposition of IL-β,TNF-α of the pathological section was respectively made on Day 1,3 and 7 after the surgery.Results On Day 1,3 and 7 after surgery,both the aspartate aminotransferase (AST) and the alanine aminotransferase (ALT) levels in NCPB group were,to different degrees,lower than those in the control group (P ＜ 0.05).Strikingly,total bilirubin in NCPB group was lower than that in control group (P ＜ 0.01) on Day 7,while the level of semm albumin was higher than that in control group (P ＜ 0.01).There was no statistically significant difference on the generation of the remaining livers between NCPB and control groups.On Day 3 and 7,the deposition of IL-β,TNF-α in the pathological sections of NCPB group were lower than those in control group.Conclusion NCPB can not only effectively reduce the damage of liver function caused by PH surgery,but also improve the inflammatory reaction of the residual liver.
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BACKGROUND: Liver regeneration (LR) after 2/3 partial hepatectomy (PH) is one of the most studied models of cell, organ, and tissue regeneration. Although the transcriptional profile analysis of regenerating liver has been carried out by many reserachers, the dynamic protein expression profile during LR has been rarely reported up to date. Therefore, this study aims to detect the global proteomic profile of the regenerating rat liver following 2/3 hepatectomy, thereby gaining some insights into hepatic regeneration mechanism. RESULTS: Protein samples extracted from the sham-operated and the regenerating rat livers at 6, 12, 24, 72, 120 and 168 h after PH were separated by IEF/SDS-PAGE and then analyzed by MALDI-TOF/TOF mass spectrometry. Compared to sham-operated groups, there were totally 220 differentially expressed proteins (including 156 up-regulated, 62 down-regulated, and 2 up/down-regulated ones) identified in the regenerating rat livers, and most of them have not been previously related to liver regeneration. According to the expression pattern analysis combined with gene functional analysis, it showed that lipid and carbohydrate metabolism were enhanced at the early phase of LR and continue throughout the regeneration process. Ingenuity Pathway Analysis indicated that YWHAE protein (one of members of the 14-3-3 protein family) was located at the center of pathway networks at all the timepoints after 2/3 hepatectomy under our experimental conditions, maybe suggesting a central role of this protein in regulating liver regeneration. Additionally, we also revealed the role of Cdc42 (cell division cycle 42) in the termination of LR. CONCLUSIONS: For the first time, our proteomic analysis suggested an important role of YWHAE and pathway mediated by this protein in liver regeneration, which might be helpful in expanding our understanding of LR amd unraveling the mechanisms of LR.
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Animals , Rats , Proteomics , Hepatectomy , Liver/metabolism , Liver Regeneration/physiology , Time Factors , Protein Biosynthesis/physiology , Body Weight/physiology , Electrophoresis, Gel, Two-Dimensional , Signal Transduction/physiology , Random Allocation , Blotting, Western , Rats, Sprague-Dawley , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , cdc42 GTP-Binding Protein/metabolism , 14-3-3 Proteins/metabolism , Electrophoresis, Polyacrylamide Gel , Carbohydrate Metabolism/physiology , Lipid Metabolism/physiology , Liver/anatomy & histologyABSTRACT
BACKGROUND: Aneuploidy has been suggested as one of the major causes of cancer from the time of Boveri. In support of this notion, many studies have shown that cancer cells exhibit aneuploidy. However, there are evidences that do not support the aneuploidy hypothesis. We have previously reported that the spindle assembly checkpoint protein BubR1 is acetylated in mitosis and that the acetylation of BubR1 is crucial for checkpoint maintenance and chromosome-spindle attachment. Mice heterozygous for acetylation-deficient BubR1 (K243R/+) spontaneously develop cancer with chromosome instability. As K243R/+ mice develop hepatocellular carcinoma, we set out to test if chromosome mis-segregation was the cause of their liver cancer. METHODS: Primary hepatocytes in the regenerating liver after partial hepatectomy (PH) were analyzed and compared for various mitotic parameters. RESULTS: Primary hepatocytes isolated from K243R/+ mice after PH displayed a marked increase of chromosome misalignment, accompanied by an increase of micronuclei. In comparison, the number of nuclei per cell and the centrosome numbers were not different between wild-type and K243R/+ mice. Taken together, chromosome mis-segregation provokes tumorigenesis in mouse liver. CONCLUSION: Our results corroborate that PH provides a reliable tool for assessing mitotic infidelity and cancer in mice.