ObjectiveTo investigate the role of endoplasmic reticulum stress in liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS).MethodsSeventy-two C57bl/6 mice were randomly divided into ALPPS group, portal vein ligation group (PVL group), and sham operation group (Sham group), 24 mice in each group. And then one-stage ALPPS operation, simple PVL, and sham operation will be performed. Six mice were randomized selected of the three groups on the 1st, 2nd, 4th, and 7th day after surgery, respectively, the liver weight to body weight ratio (FLR/BW) of each group was measured, and the liver tissues were taken for immunohistochemical staining to calculate the proportion of Ki-67 positive cells, Western blot was used to detect the expression levels of X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) proteins.Results① FLR/BW: On the 4th day and the 7th day after operation, the FLR/BW of the Sham group, PVL group, and ALPPS group increased in sequence at the same time, and the difference between the three groups was statistically significant (P<0.05). ② Ki-67 positive cell ratio: On the 2nd day after operation, the ratio of Ki-67 positive cells in the Sham group, PVL group, and ALPPS group increased sequentially, and the difference between the two groups was statistically significant (P<0.05). On the 4th day after operation, the ratio of Ki-67 positive cells in the PVL group and the ALPPS group were still higher than that of the Sham group (P<0.05). ③ Expression levels of XBP1 and IRE1α: On the 2nd and 4th postoperative day, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group and the PVL group (P<0.05). On the 7th day after surgery, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group (P<0.05), while compared with the PVL group, the expression level of XBP1 in the ALPPS group was still higher (P<0.05).ConclusionsALPPS-induced liver regeneration is more advantageous than traditional PVL in mice. It may be attributed to the obvious endoplasmic reticulum stress activation after ALPPS leading to the up-regulation of IRE1α-XBP1 expression, which is involved in the regulation of hepatocyte cell cycle and promotes hepatocyte proliferation, thus promoting rapid liver regeneration.
Objective To examine the effect of zinc finger protein A20 on regeneration of small-for-sized liver allograft, graft rejection and recipient rat survival time. Methods Small-for-sized liver transplantation with 30% partial liver allograft was performed by using a b-rejection combination rat model of DA (RT1a) to Lewis (RT1l) rats. The rats were grouped into rAdEasy-A20 treatment group （A20 group）, the control empty Ad vector rAdEasy treatment group (rAdEasy group) and PS control treatment group (PS group). Ex vivo gene transfer in donor liver graft was performed through portal vein infusion. Animals were assessed for survival days, expression of A20 in liver graft, liver graft regeneration, hepatocyte apoptosis, graft rejection, NF-κB activation and ICAM-1 mRNA expression in liver graft sinusoidal endothelial cells (LSECs), number of liver graft infiltrating mononuclear cells (LIMCs) and the subproportion of NK/NKT cells, and serum IFN-γ level. Results Survival day of A20 group rats was prominently longer than that of PS group rats and rAdEasy group rats (P=0.001 8), whereas survival day of rAdEasy group rats was remarkably shorter than that of PS group rats (P=0.001 8). Regeneration of the small-for-sized liver allograft was markedly augmented by A20, BrdU labelling index of hepatocyte on postoperative day 4 was significantly increased in the A20 group compared with the PS group and rAdEasy group (P＜0.01). Hepatocyte apoptosis on postoperative day 4 was significantly inhibited by A20 (P＜0.01). On postoperative day 4, histologic examination revealed a mild rejection in the A20 group but a more severe rejection in the PS and rAdEasy groups. NF-κB activity and ICAM-1 mRNA expression in LSECs on postoperative day 1 were notably suppressed by A20 overexpression. Flow cytometry analysis showed a marked downregulation of LIMCs number by A20, including more prominent decrease in the subproportion of NK/NKT cells on postoperative day 1 and 4, respectively (P＜0.05). Serum IFN-γ level on postoperative day 4 was also significantly suppressed by A20 overexpression (P＜0.05). Conclusion These data suggest that A20 could effectively promote small-for-sized liver allograft regeneration, suppresses rejection and prolong survival days of recipient rats. These effects of A20 could be related to an inhibition of LSECs activation, suppression of infiltration of LIMCs and the subpopulations such as NK cells and NKT cells into liver graft, and inhibition of hepatocyte apoptosis.
Objective To analyze and summarize the research progression of phenotypic markers of hepatic sinusoidal endothelial cell （HSEC） and its role in the development and progression of the liver diseases. Methods Databases such as PubMed， Wanfang， CNKI， etc were retrieved for the latest articles on research advance in HSEC using “hepatic sinus endothelial cell”， “liver regeneration”， and “liver disease” as key words. All of the publications about studies on relation between HSEC and liver disease were reviewed and summarized. Results HSEC with specific cytoarchitectures and phenotypic markers was initially received “the message of damage” in the process of liver regeneration， hepatic immunological tolerance， hepatic fibrosis， and liver damage. Additionally， HSEC as the first barrier not only enabled liver to be protected but also was regarded as the first alternation of liver damage. Therefore， HSEC played a great important role in the process of the onset and progression of the liver disease. Conclusions The function of HSEC is complex. How do play a role and its the mechanism is unclarified， it is needed to be further studied.
ObjectiveTo summarize the progress of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and evolution of surgical procedure improvement, so as to summarize experience in selecting appropriate surgical method for patients. MethodThe domestic and foreign literature on the evolution of ALPPS surgical procedure improvement in recent years was reviewed. ResultsIn the decade since the emergence of ALPPS, the ALPPS had been rapidly developed in the hepatobiliary surgery. The ALPPS promoted a rapid increase in future liver remnant during a relatively shorter period to contribute to resectability of liver tumors and reduce the rate of postoperative liver failure, the patients with intermediate to advanced and huge liver cancer could obtain the surgical radical resection. In recent years, the domestic and foreign experts had refined the ALPPS procedure, which mainly focused on the operation of hepatic section separation and hepatic artery flow restriction in stage Ⅰ surgery, including partial ALPPS, radiofrequency ablation ALPPS, tourniquet ALPPS, transcatheter arterial embolization ALPPS, hepatic artery ringed and operation ALPPS, as well as laparoscopic ALPPS and robotic ALPPS with minimally invasive approach. ConclusionsDespite the ongoing controversy over ALPPS, with the continuous progress and innovation of improved procedures and the utilization of laparoscope and robot in surgery, the trauma of ALPPS surgery has a further reduction, and the morbidity and mortality have gradually been decreased. It is believed that with the continuous advancement and improvement of ALPPS surgery technology, the indications and safety of ALPPS will be further enhanced, bringing hope to more patients with intermediate to advanced liver cancer with huge tumors.
ObjectiveTo understand the latest development in lineage tracing techniques and their applications in the study of liver regeneration mechanisms. MethodA review of domestic and international literature on the application of lineage tracing techniques in liver regeneration was conducted. ResultsA variety of more reliable and advanced lineage tracing techniques had been developed, such as single-cell RNA sequencing, DNA barcode technology, etc., providing powerful tools for a deeper understanding of the mechanisms of liver regeneration. The marked progress had been made in identifying the origins of liver regeneration cells, identifying liver regeneration areas, and studying the mechanisms of liver regeneration after injury. The lineage tracing techniques help to understand the position and function of different types of liver cells within the liver structure, revealing the regenerative potential and contribution of different subpopulations of liver cells. Moreover, these techniques had supported the phenomenon of transdifferentiation between the hepatocytes and the bile duct cells under chronic liver injury conditions, aiding in understanding the specific roles of key signaling pathways in liver regeneration, such as Wnt/β-catenin, Hippo/YAP, and Notch signaling pathways.ConclusionsAlthough lineage tracing techniques have made marked progress in liver regeneration research, liver regeneration is a complex and important physiological process, and the technique still has limitations, such as challenges in marker specificity, longer research cycles and higher costs, potential limitations in translating from animal models to human clinical applications, inability to solve all questions about liver regeneration mechanisms, and ethical and legal issues. Therefore, more in-depth and comprehensive research is still needed to reveal more details of liver regeneration mechanism.
ObjectiveTo investigate the protective effect of SadenosylLmethionine on liver regeneration and
liver function in cirrhotic rats after hepatectomy. MethodsCirrhosis was successfully induced by injection of 40%
CCl4.Then,partial hepatectomy (about 30%) was performed in all rats. Cirrhotic rats were divided into 3
groups,namely,cirrhotic group (normal saline 5 ml/d,for 15 postoperative days，n=20),treatment group 1 〔S
adenosylLmethionine 10 mg/(kg·d),for 15 postoperative days,n=16〕 and treatment group 2 〔SadenosylL
methionine 20 mg/(kg·d),15 postoperative days,n=16〕,and normal control group was also established. Animals were
sacrificed at the 15th postoperative day and 30th postoperative day to take samples for detection of liver
function (Alb,ALT,TB,TBA) and serum TNFα.Liver tissues were also observed under light microscope and electron
microscope. ResultsIn two treatment groups,at the time point (15 postoperative days or 30 postoperative
days),concentrations of ALT,TB,TBA,Alb and TNFα were decreased significantly as compared with cirrhotic group (P
＜0.01),and concentration of Alb was increased significantly (P＜0.01).In contrast, there were no obvious difference
in the same time point of different dosetreatment groups (Pgt;0.05),but the decrease of ALT,TB,TBA,TNFα and the
increase of Alb were more significant at the second time point (30th postoperative day) than the first time
point (15th postoperative day) when treated with same dose (P＜0.01).At the same time,concentration between TNF
α and ALT,TB,TBA showed a positive correlation (P＜0.01),and the concentration between TNFα and Alb showed a
negative correlation (P＜0.01).In addition, the histopathology showed SadenosylLmethionine had effects of
protecting liver function and enhancing liver regeneration. ConclusionThe study suggests that SadenosylL
methionine has the efficacy of enhancing liver regeneration and improving liver function.
Objetive
To summarize the mechanism and the application of the research on liver regeneration.
Methods
The related literatures about enteral liver regeneration in recent years were reviewed.
Results
Even though liver regeneration after liver resection has been widely studied, we can get better understanding from new clinical application. The process of regeneration induced liver injury rarely occurs in the normal liver. Many studies have focused on the mechanism of liver cell regeneration after liver injury. For example, the study of liver regeneration related factors and liver regenerative cells, but the specific mechanism is still not very clear. Recent techniques using the obvious progress in understanding liver regeneration are portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another involved in liver regeneration is the main field of stem cell therapy.
Conclusion
Great understanding liver regeneration should provide to the development of new treatment strategies and diagnostic procedures for various liver diseases.
Augmenter of liver regeneration (ALR) is a newly discovered cytokine that can promote liver regeneration and proliferation of damaged liver cells. In the renal tissue, ALR is mainly expressed in the cytoplasm of the medullary loops, collecting ducts and distal convoluted tubules in the renal medulla, and is low in the glomerular and cortical tubules. Various stimulation, such as ischemiacal, hypoxia, poisoning and inflammatory stimulation, can induce the expression of ALR in the epithelial cells of proximal tubule regeneration and the damaged areas of cortex, and participate in the repair process. Current studies have found that in acute kidney injury (AKI), exogenous ALR can protect renal tubular epithelial cells by inhibiting apoptosis of renal tubular epithelial cells, promoting proliferation of renal tubular epithelial cells, inhibiting the activities of inflammatory cells, and promoting the reduction of renal injury. This paper intends to review the basic characteristics of ALR and the pathogenesis of AKI, summarize the characteristics of the mechanism of ALR in AKI by combing the relevant literature on ALR and AKI in recent years, and provide knowledge reserve and direction reference for the in-depth study of ALR in kidney in the future.
【Abstract】 Objective To study liver regeneration of the non-ligated liver lobes following portal branch ligation (PBL). Methods Sixty male Wistar rats were randomly divided into PBL group and sham operation (SO) group. Under ether anesthesia, the rats were subjected to PBL and sham operation, respectively. The animals were sacrificed on the 1st, 2nd, 3rd, 7th and 14th day respectively. The blood sample was collected from heart and the livers were harvested to determine serum alanine aminotransferase (ALT) levels and total liver weight, respectively. The hepatic histopathology was studied through light microscopy. The number of liver cell nuclear mitosis index was counted. The number of proliferative cell nuclear antigen (PCNA) index was counted by immunohistochemistry. The hepatic ultrastructural changes were studied under electron microscope. Results ①Elevated serum ALT level was observed in the first postoperative day in PBL group compared with SO group (P＜0.01)， but began to recover in the second day. ②No significant total liver weight change in PBL group and SO group were found. ③Liver cell nuclear mitosis index and PCNA index were markedly increased in PBL group compared with SO group in day 1-3 postoperative day (P＜0.01). It reached the peak in the second day and decreased slightly in the 3rd day, but still higher than SO group, then gradually return to normal lately. Conclusion The ligation of left portal branch can induce active regeneration of hepatic cell of non-ligated liver lobes in rats. The regeneration of non-ligated liver lobes may restore previous total liver weight. The ligation of 75% portal branch does not affect liver function and may be safely performed. The portal branch ligation in rats may be used as an animal model in study of liver regeneration.
