In order to observe the effect of hepatocyte growth promoting factor (pHGF) on liver regeneration of rat with cirrhosis after hepatectomy, IBAS Ⅱ auto image analysis technology was used to measure the variety of DNA ploid rate of hepatocytes and OPTDM of enzymes by liver histochemistry after hepatectomy; serum levels of the glutamicpyruvic transaminase (SGPT) and indocyanine green retention rate in 15 minute (ICG15) were tested to measure the function of the remanent liver. The results revealed that tetraploid hepatocytes lowered greatly and diploid, quintploid and ＞quintploid hepatocytes increased apparently in group A. OPTDM of enzymes by liver histochemistry showed no significant difference at the first day after operation in each group (Ｐ＞0.05); SDH and LDH of group A were significantly higher than those of group B and AkP, AcP were significantly lower at the second or fifth day after hepatectomy. Serum tests showed that SGPT, ICG15 of group A decreased apparently at the fifth day after operation. The results demonstrate that pHGF not only stimulates the regeneration of the remanent liver but also accelerates the functional mature of the regenerative hepatocytes and the functional recovery of the remanent liver after resection of cirrhotic liver of rats.
【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.
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.
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.
Objective To summarize the research progress on the regulation of hepatic sinusoidal microenvironment to promote liver regeneration based on liver sinusoidal endothelial cells (LSECs), aiming to further clarify the mechanism of liver regeneration and provide new ideas and methods for clinical promotion of liver regeneration and prevention of liver failure. Method The basic and clinical research studies on LSECs and liver regeneration at home and abroad in recent years were searched and reviewed. Results Differentiated LSECs played an important role in liver regeneration, regulated the homeostasis of hepatic sinusoid microenvironment by paracrine and autocrine, and participated in the whole process of promoting liver regeneration, such as hepatocyte proliferation and neovascularization after acute and chronic liver injury. Conclusion In the process of liver regeneration after all kinds of acute and chronic liver injury, LSECs promote liver regeneration by regulating hepatic sinusoid microenvironment, which will provide new strategies and methods for clinical promotion of liver regeneration and prevention of liver failure after hepatectomy.
Extensive hepatectomy can achieve a higher chance of radical resection of lesions in the hepatobiliary system, but the risk of fatal complications of severe liver failure after surgery also increases accordingly. Therefore, enhancing the liver’s regenerative capacity has always been a hot topic in clinical research. Portal vein blood supply is of great significance for maintaining the normal function of the liver and promoting the repair and proliferation of damaged liver tissue. After selectively altering the blood flow distribution in the portal vein, atrophy or proliferation will occur in different liver lobes. The discovery of the important physiological phenomenon of liver regeneration induced by deportalized blood flow of portal vein has made it possible to promote the volume growth and functional enhancement of the residual liver lobes before hepatectomy, and various technical schemes have been applied and developed in clinical practice. The interim research results show that the portal vein embolization technique is mature, has less trauma, but the induction speed is relatively slow. Portal vein combined with hepatic vein embolization has better induction efficacy and does not increase embolism-related complications, and has a wider range of applications. The induction ability of associating liver partition and portal vein ligation for staged hepatectomy is significant, but the surgical trauma is large, and there are higher requirements for perioperative management. There is a clear correlation between high surgical volume centers and technical improvements and a significant reduction in complications. Resection and partial liver transplantation with delayed total hepatectomy not only break through the bottlenecks of safety and ethical requirements for living donor liver transplantation in adults, but also innovate and enrich the second-stage extensive hepatectomy schemes. However, their technical standards and application scope still need more high-quality research evidence to support them.
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.
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.