Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury

Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding RNAs(lnc RNAs)and micro RNAs(mi RNAs)have been identified as factors involved in the pathological progression of HIRI.In this review,we summarized the latest research on lnc RNAs,mi RNAs and the lnc RNA-mi RNA regulatory networks in HIRI.Data sources:The Pub Med and Web of Science databases were searched for articles published up to December 2021 using the following keywords:“hepatic ischemia-reperfusion injury”,“lnc RNA”,“long noncoding RNA”,“mi RNA”and“micro RNA”.The bibliography of the selected articles was manually screened to identify additional studies.Results:The mechanism of HIRI is complex,and involves multiple lnc RNAs and mi RNAs.The roles of lnc RNAs such as AK139328,CCAT1,MALAT1,TUG1 and NEAT1 have been established in HIRI.In addition,numerous mi RNAs are associated with apoptosis,autophagy,oxidative stress and cellular inflammation that accompany HIRI pathogenesis.Based on the literature,we conclude that four lnc RNA-mi RNA regulatory networks mediate the pathological progression of HIRI.Furthermore,the expression levels of some lnc RNAs and mi RNAs undergo significant changes during the progression of HIRI,and thus are potential prognostic markers and therapeutic targets.Conclusions:Complex lnc RNA-mi RNA-m RNA networks regulate HIRI progression through mutual activation and antagonism.It is necessary to screen for more HIRI-associated lnc RNAs and mi RNAs in order to identify novel therapeutic targets.

COVID-19 and hepatic injury: cellular and molecular mechanisms in diverse liver cells

The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.

Non-coding RNAs:The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury

Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mechanisms have been extensively investigated in recent years.Among these,oxidative stress,inflammatory responses,immunoreactions,and cell death are the most studied.Non-coding RNAs(ncRNAs)are defined as the RNAs that do not encode proteins,but can regulate gene expressions.In recent years,ncRNAs have emerged as research hotspots for various diseases.During the progression of HIRI,ncRNAs are differentially expressed,while these dysregulations of ncRNAs,in turn,have been verified to be related to the above pathological processes involved in HIRI.ncRNAs mainly contain microRNAs,long ncRNAs,and circular RNAs,some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity,and as therapeutic targets to attenuate HIRI.Here,we briefly summarize the common pathophysiology of HIRI,describe the current knowledge of ncRNAs involved in HIRI in animal and human studies,and discuss the potential of ncRNA-targeted therapeutic strategies.Given the scarcity of clinical trials,there is still a long way to go from pre-clinical to clinical application,and further studies are needed to uncover their potential as therapeutic targets.

Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis （SAP） in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death, lts complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR （oxygen free radical）, endotoxin, etc. may play important roles in its progression.

Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion

AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.

Study on protecting effects of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.

Two clinically relevant pressures of carbon dioxide pneumoperitoneum cause hepatic injury in a rabbit model

AIM:To observe the hepatic injury induced by carbon dioxide pneumoperitoneum(CDP) in rabbits,compare the eects olow-and high-pressure pneumoperitoneum,and to determine the degree o hepatic injury induced by these two clinically relevant CDP pressures.METHODS:Thirty healthy male New Zealand rabbits weighing 3.0 to 3.5 kg were randomly divided into three groups(n = 10 for each group) and subjected to the ollowing to CDP pressures:no gas control,10 mmHg,or 15 mmHg.Histological changes in liver tissues were observed with hematoxylin and eosin staining and transmission electron microscopy.Liver unction was evaluated using an automatic biochemical analyzer.Adenine nucleotide translocator(ANT) activity in liver tissue was detected with the atractyloside-inhibitor stop technique.Bax and Bcl-2 expression levels were detected bywestern blotting.RESULTS:Liver Functions in the 10 mmHg and 15 mmHg experimental groups were significantly disturbed compared with the control group.After CDP,the levels or alanine transaminase and aspartate transaminase were 77.3 ± 14.5 IU/L and 60.1 ± 11.4 IU/L,respectively,in the 10 mmHg experimental group and 165.1 ± 19.4 IU/L and 103.8 ± 12.3 IU/L,respectively,in the 15 mmHg experimental group,which were all higher than those of the control group(p < 0.05).There was no difference in pre-albumin concentration between the 10 mmHg experimental group and the control group,but the prealbumin level of the 15 mmHg experimental group was significantly lower than that of the control group(p < 0.05).No significant differences were observed in the levels of total bilirubin or albumin among the three groups.After 30 and 60 min of CDP,pH was reduced(p < 0.05) and fa CO2 was elevated(p < 0.05) in the 10 mmHg group compared with controls,and these changes were more pronounced in the 15 mmHg group.Hematoxylin and eosin staining showed no significant change in liver morphology,except for mild hyperemia in the two experimental groups.Transmission electron microscopy showed mild mitochondrial swelling in hepatocytes of the 10 mmHg group,and this was more pronounced in the 15 mmHg group.No significant difference in ANT levels was found between the control and 10 mmHg groups.However,ANT concentration was significantly lower in the 15 mmHg group compared with the control group.The expression of hepatic Bax was significantly increased in the two experimental groups compared with the controls,but there were no differences in Bcl-2 levels among the three groups.Twelve hours after CDP induction,the expression of hepatic Bax was more significant in the 15 mmHg group than in the 10 mmHg group.CONCLUSION:A CDP pressure of 15 mmHg caused more substantial hepatic injury,such as increased levels of acidosis,mitochondrial damage,and apoptosis;therefore,10 mmHg CDP is preferable for laparoscopic operations.

Hepatic injury induced by carbon dioxide pneumoperitoneum in experimental rats

AIM： To observe the hepatic injury induced by carbon dioxide pneumoperitoneum in rats and to explore its potential mechanism.METHODS： Thirty healthy male SD rats were randomly divided into control group （n = 10）, 0 h experimental group （n = 10） and 1 h experimental group （n = 10） after sham operation with carbon dioxide pneumoperitoneum. Histological changes in liver tissue were observed with hematoxylineosin staining. Liver function was assayed with an automatic biochemical analyzer. Concentration of malonyldialdehyde （MDA） and activity of superoxide dismutase （SOD） were assayed by colorimetry. Activity of adenine nucleotide translocator in liver tissue was detected with the atractyloside-inhibitor stop technique. Expression of hypoxia inducible factor-1 （HIF-1） mRNA in liver tissue was detected with in situ hybridization.RESULTS： Carbon dioxide 60 min could induce liver pneumoperitoneum for injury in rats. Alanine aminotransferase and aspartate aminotransferase were 95.7 ± 7.8 U/L and 86.8 ± 6.9 U/L in 0 h experimental group, and 101.4 ± 9.3 U/L and 106.6 ±8.7 U/L in 1 h experimental group. However, no significant difference was found in total billirubin, albumin, and pre-albumin in the three groups. In 0 h experimental group, the concentration of MDA was 9.83 ±2.53 μmol/g in liver homogenate and 7.64 ± 2.19 μmol/g in serum respectively, the activity of SOD was 67.58±9.75 nu/mg in liver and 64.47 ± 10.23 nu/mg in serum respectively. In 1 h experimental group, the concentration of MDA was 16.57±3.45 μmol/g in liver tissue and 12.49 ±4.21 μmol/g in serum respectively, the activity of SOD was 54.29 ±7.96 nu/mg in liver tissue and 56.31 ±9.85 nu/mg in serum respectively. The activity of ANT in liver tissue was 9.52 ± 1.56 in control group, 6.37± 1.33 in 0 h experimental group and 7.2 8±1.45 （10^-9 mol/min per gram protein） in 1 h experimental group, respectively. The expression of HIF-1 mRNA in liver tissue was not detected in control group, and its optical density difference value was 6.14±1.03 in 0 h experimental group and 9.51 ± 1.74 in 1 h experimental group, respectively. CONCLUSION： Carbon dioxide pneumoperitoneum during the sham operation can induce hepatic injury in rats. The probable mechanisms of liver injury include anoxia, ischemia reperfusion and oxidative stress. Liver injury should be avoided during clinical laparoscopic operation with carbon dioxide pneumoperitoneum.

Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50μg/kg pcDNA3-ALR DNA.The effect of intravenous injection of recombinant pcDNA3ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid,the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P＜0.01).CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level ofAST and ALT in CCl4-intoxicated rats.

New progress in roles of nitric oxide during hepatic ischemia reperfusion injury

Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1 alpha-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.

Ex vivo-expanded bone marrow stem cells home to the liver and ameliorate functional recovery in a mouse model of acute hepatic injury

BACKGROUND:Stem cell transplantation provides a theoretical approach for liver regeneration medicine;it may promote liver regeneration and self-repair.However,the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated.This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl 4 injury.METHODS:Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation,characterized by cytoflow immunofluorescence,and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl 4.The integration of bone marrow cells into the liver was examined microscopically,and plasma hepatic enzymes were determined biochemically.RESULTS:Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells.Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl 4 -treated mice.Densitometry showed increased in situ cell proliferation (50±14 vs 20±3 cells/high-power field,P<0.05) and albumin expression (149±25 vs 20±5 cells/high-power field,P<0.05) in the liver,as well as reduced serum aminotransferase levels (P<0.05) and better survival rates (P<0.05) in animals receiving cultured bone marrow cells relative to controls.CONCLUSIONS:Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically- injured liver.Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.

Fisetin mitigates hepatic ischemia-reperfusion injury by regulating GSK3β/AMPK/NLRP3 inflammasome pathway

Background: Hepatic ischemia-reperfusion(I/R) injury(IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine whether fisetin mitigates hepatic IRI and examine its underlying mechanisms. Methods: Sham or warm hepatic I/R operated mice were pretreated with fisetin(5, 10 or 20 mg/kg). Hepatic histological assessments, TUNEL assays and serum aminotransferase measurements were performed. An in vitro hypoxia/reoxygenation(H/R) model using RAW264.7 macrophages pretreated with fisetin(2.5, 5 or 10 μmol/L) was also used. Serum and cell supernatant concentrations of interleukin-1 β(IL-1 β), IL-18 and tumor necrosis factor-α(TNF-α) were determined by enzyme-linked immunosorbent assay(ELISA). Protein levels of p-GSK3 β, p-AMPK and NLR family pyrin domain-containing 3(NLRP3)-associated proteins were detected by Western blotting. Results: Compared with the I/R group, fisetin pretreatment reduced pathological liver damage, serum aminotransferase levels, serum concentrations of IL-1 β, IL-18 and TNF-α in the murine IRI model. Fisetin also reduced the expression of NLRP3 inflammasome-associated proteins(NLRP3, cleaved caspase-1, IL-1 β and IL-18) in I/R-operated liver. The experiments in vitro showed that fisetin decreased the release of IL-1 β, IL-18 and TNF-α, and reduced the expression of NLRP3 inflammasome-associated proteins in H/R-treated RAW264.7 cells. Moreover, fisetin increased the expressions of p-GSK3 β and p-AMPK in both models, indicating that its anti-inflammatory effects were dependent on GSK3 β/AMPK signaling. The antiinflammatory effects of fisetin were partially inhibited by the AMPK specific inhibitor compound C. Conclusions: Fisetin showed protective effects against hepatic IRI, countering inflammatory responses through mediating the GSK3 β/AMPK/NLRP3 inflammasome pathway.

Pathological and MR-DWI study of the acute hepatic injury model after stem cell transplantation

AIM： To investigate apparent diffusion coefficient （ADC） values as an indication of reconditioning of acute hepatic injury （AHI） after allogeneic mononuclear bone marrow cell （MBMC） transplantation. METHODS： Three groups were used in our study： a cell transplantation group （n = 21）, transplantation control group （n = 21） and normal control group （n = 10）. AHI model rabbits in the cell transplantation group were injected with 5 mL of MBMC suspension at multiple sites in the liver and the transplantation controls were injected with 5 mL D-Hanks solution. At the end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell transplantation group and trans- plantation control group for magnetic resonance diffu- sion-weighted imaging （MR-DWI） and measurement of the mean ADC values of injured livers. After MR-DWI examination, the rabbits were sacrificed and the livers subjected to pathological examination. Ten healthy rab- bits from the normal control group were used for MR- DWI examination and measurement of the mean ADC value of normal liver. RESULTS： At all time points, the liver pathological scores from the cell transplantation group were significantly lower than those in the transplantation control group （27.14± 1.46 vs 69.29± 6.16, 22.29 ± 2.29 vs 57.00± 1.53, 19.00 ± 2.31 vs 51.86 ± 6.04, P = 0.000）. The mean ADC values of the cell transplantation group were significantly higher than the transplantation con- trol group （（1.07± 0.07） ×10^-3 mm2/s vs （0.69 ± 0.05） ×10^-3 mm2/s, （1.41± 0.04） ×10^-3 mm2/s vs （0.84± 0.03） ×10^-3 mm2/s, （1.68 ± 0.04） ×10^-3 mm2/s vs （0.86± 0.04） ×10^-3 mm2/s, P = 0.000）. The pathological scores of the cell transplantation group and transplantation control group gradually decreased. However, their mean ADC values gradually increased to near that of the normal control. At the end of the 1st wk, the mean ADC values of the cell transplantation group and transplantation control group were significantly lower than those of the normal control group [（1.07 ± 0.07） ×10^-3 mm2/s vs （± 0.03） ×10^-3 mm2/s, （0.69± 0.05） ×10^-3 mm2/s vs （1.76 ± 0.03） ×10^-3 mm2/s, P = 0.000]. At any 2 time points, the pathological scores and the mean ADC values of the cell transplantation group were significantly different （P = 0.000）. At the end of the 1st wk, the pathological scores and the mean ADC values of the transplantation control group were significantly different from those at the end of the 2nd and 4th wk （P = 0.000）. However, there was no significant difference between the 2nd and 4th wk （P = 0.073 and 0.473, respectively）. The coefficient of correlation between the pathological score and the mean ADC value in the cell transplantation group was -0.883 （P = 0.000） and -0.762 （P = 0.000） in the transplantation control group. CONCLUSION： Tracking the longitudinally dynamic change in the mean ADC value of the AHI liver may reflect hepatic injury reconditioning after allogeneic MBMC transplantation.

Clinical studies on inferior right hepatic veins

BACKGROUND: Many small veins are called accessory, short hepatic veins in addition to the right, middle and left hepatic veins. The size of these veins varied from a pinhole to 1 cm; the size of inferior right hepatic veins (IRHVs) is thicker than that of short hepatic veins or more than 1 cm. occasionally. Adults have a higher incidence rate of the IRHV. DATA SOURCES: A literature search of the PubMed database was conducted and research articles were reviewed. RESULTS: The size of IRHVs is related to the size of the right hepatic vein, i.e. the larger the diameter of the right hepatic vein, the smaller the diameter of the IRHVs, and vice versa. The IRHVs are divided into superior, medial and inferior groups, separately named the superior, medial and inferior right hepatic veins according to the position of the IRHV entering the inferior vena cava. The superior right hepatic vein mainly drains the superior part of segment VII, and the medial right hepatic vein drains the middle part of segment VII. A thicker IRHV mainly drains segment VI and the inferior part of segment VII and a thinner IRHV drains the inferior part of segment V. CONCLUSIONS: The clinical significance of these studies on IRHVs is varied: (1) Hepatic caudate lobe resection could be introduced after study on the veins of that lobe. (2) It is very important to identify the draining region of the IRHV for guiding hepatic segmentectomy. The postero-inferior area of the right lobe can be preserved along with the hypertrophic IRHV even if the entire main right hepatic vein is resected during segmentectomy of VII and VIII with right hepatic vein resection for patients with primary liver cancer. (3) The ligation of the major hepatic vein for the treatment of juxtahepatic vein injury is recommended because of severe hemorrhagic shock and difficulty in exposure. (4) It is very helpful to decide therapeutic modalities for Budd-Chiari syndrome.

Dimethylacetamide-induced Hepatic Injury in Vitro: Mechanism and Potential Preventive Strategy

N,N-Dimethylacetamide （DMAc） is a widely used organic solvent in modern chemical industry with low to moderate hepatotoxicity to occupational health of employees. But so far, there are fewer and less conclusive data concerning its pathogenic mechanism in detail. In current study, the toxicity of DMAc was firstly investigated on human normal hepatocytes （LO-2）, using a series of molecular biology measurements to ananlyze the effect and mechanism of DMAc-induced hepatic cell injury and explore effective prophylactic measures. We found that DMAc triggered LO-2 apoptosis in a obviously dose-dependent manner, caused by increased ROS generation and activation of Bcl-2 pathway. Significantly, glutathione （GSH） rather than vitamin C （Vit C） could partially inhibit DMAc-induced apoptosis thus showing potential as a effective precaution for workers.

Surgical management in biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury

AIM: To discuss the surgical method and skill of biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury. METHODS: From November 2005 to December 2006, eight patients with biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury were admitted to our hospital. Their clinical data were analyzed retrospectively. RESULTS: Bile duct injury was caused by cholecys- tectomy in the eight cases, including seven cases with laparoscopic cholecystectomy and one with mini- incision choleystectomy. According to the classification of Strasberg, type E1 injury was found in one patient, type E2 injury in three, type E3 injury in two and type E4 injury in two patients. Both of the type E4 injury patients also had a vascular lesion of the hepatic artery. Six patients received Roux-en-Y hepaticojejunostomy for the second time, and one of them who had type E4 injury with the right hepatic artery disruption received right hepatectomy afterward. One patient who had type E4 injury with the proper hepatic artery lesion underwent liver transplantation, and the remaining one with type E3 injury received external biliary drainage. All the patients recovered fairly well postoperatively. CONCLUSION: Roux-en-Y hepaticojejunostomy is still the main approach for such failed surgical cases with bile duct injury. Special attention should be paid to concomitant vascular injury in these cases. The optimal timing and meticulous and excellent skills are essential to the success in this surgery.

Role of adhesion molecules and dendritic cells in rat hepatic/renal ischemia-reperfusion injury and anti-adhesive intervention with anti-P-selectin lectin-EGF domain monoclonal antibody

AIM: To investigate the role of P-selectin, intercellular adhesion molecule-1 (ICAM-1) and dendritic cells (DCs)in liver/kidney of rats with hepatic/renal ischemiareperfusion injury and the preventive effect of anti-Pselectin lectin-EGF domain monoclonal antibody (anti-PsLEGFmAb) on the injury.METHODS: Rat models of hepatic and renal ischemiareperfusion were established. The rats were then divided into two groups, one group treated with anti-PsL-EGFmAb(n = 20) and control treated with saline (n = 20). Both groups were subdivided into four groups according to reperfusion time (1, 3, 6 and 24 h). The sham-operated group (n = 5) served as a control group. DCs were observed by the microscopic image method, while P-selectin and ICAM-1 were analyzed by immunohistochemistry.RESULTS: P-selectin increased significantly in hepatic sinusoidal endothelial cells and renal tubular epithelial cells 1 h after ischemia-reperfusion, and the expression of ICAM-1 was up-regulated in hepatic sinusoid and renal vessels after 6 h. CD1a+CD80+DCs gradually increased in hepatic sinusoidal endothelium and renal tubules and interstitium 1 h after ischemia-reperfusion, and there was the most number of DCs in 24-h group. The localization of DCs was associated with rat hepatic/renal function.These changes became less significant in rats treated with anti-PsL-EGFmAb.CONCLUSION: DCs play an important role in immune pathogenesis of hepatic/renal ischemia-reperfusion injury.Anti-PsL-EGFmAb may regulate and inhibit local DC immigration and accumulation in liver/kidney.

Protective effects of 5,4'-dihydroxy-3',5'- dimethoxy-7-O-β-D -glucopyranosyloxy-flavone on experimental hepatic injury

AIM: To investigate the pharmacological effects of rice flavone (5,4'-dihydroxy-3',5'-dimethoxy-7-0-β-D-glucopyranosyloxy-flavone, RF) separated from panicle-differentiating to flowing rice on rat experimental hepatic injury. METHODS: Models of rat acute hepatic injury induced by carbon tetrachloride (CCl4) administration, rat hepatic fibrosis induced by thioacetamide, injury of primary cultured rat hepatocytes induced by CCl4, respectively, were established. After treated with RF, content of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (Alb), hyaluronic acid (HA), the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and hydroxyproline (Hyp) were measured and liver tissue was observed pathologically by hematoxylin-eosin (HE) staining. Effects of RF on pathological changes, function index, enzyme of scavenging free radicals and blood rheology were evaluated. RESULTS: In model of rat acute hepatic injury induced by CCI4, RF can significantly decrease the contents of serum ALT, AST, increase the content of Alb, improve the dropsy and fat denaturalization of hepatocytes. In model of rat hepatic fibrosis induced by thioacetamide, RF can inhibit the increase of HA, Hyp and whole blood viscosity, and improve the activities of GSH-Px and SOD, and inauricular microcirculation. CONCLUSION: RF has apparent protective effects on hepatic injury by increasing activity of GSH-Px and SOD, scavenging free radicals produced by CCI4, reducing blood viscosity, and improving microcirculation and blood supply.

Protective Effect of Extract Powder of Turmeric on Carbon Tetrachloride Induced Acute Hepatic Injury in Mice

To explore the protective effect of extract powder of turmeric on carbon tetrachloride （CCl4）-induced acute hepatic injury, the mice were administrated with extract powder of turmeric with different doses （50, 100, 200 mg/kg） for 7 d. Then the mice were treated with 0.12% CCl4 by intraperitoneal injection. The levels of ALT, AST in serum and activities of SOD, CAT, MDA, GSH-Px in liver tissue were detected and the liver lesions were examined. The results showed that the activities of ALT, AST and the level of MDA in extract powder of turmeric group were signif- icantly decreased, and the activities of SOD, CAT, GSH-Px were significantly increased, and liver pathology were improved compared with the injured group （P〈 0.05 or P〈0.01）. It indicated that the extract powder of turmeric had significant protective effect against CCl4 induced acute hepatic injury in mice.