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1.
Article in Chinese | WPRIM | ID: wpr-932746

ABSTRACT

Objective:To investigate the changes of T1 and T2 values in residual liver after major liver resection in rats and the relationship with pathologic indices related to liver regeneration.Methods:Seventy healthy male Sprague Dawley rats, SPF grade, aged 7-8 weeks, weighting 250-280 g, were divided into MR scan group ( n=14) and pathologic analysis group ( n=56). The MR scan group was further divided into partial hepatectomy group ( n=7) and the sham operation group ( n=7). MRI T 1 mapping and T 2 mapping were performed before surgery and on day 1, 2, 3, 5, 7, 14, 21 after surgery. T1 and T2 values of liver parenchyma were measured. In the pathologic analysis group, 7 rats were randomly included at each time point before and after surgery for pathologic examination, the diameter and proliferative activity (Ki-67 indices) of hepatocytes were assessed. The changes of imaging and pathologic indices were observed, and the correlations between MR parameters and liver volume and pathologic indices were analyzed. Results:Both T1 and T2 values in liver parenchyma were increased on day 1 after surgery and reached their maximum values on day 2 ( P=0.005 and P<0.001, compared with baseline), then were gradually decreased, and recovered to the preoperative level on day 14 and 21 ( P>0.05), respectively. T2 value was correlated with hepatocyte diameter, liver volume and Ki-67 indices better ( r=0.640, -0.764, 0.765, respectively, all P<0.001). T1 value was correlated with hepatocyte diameter, liver volume and Ki-67 indices ( r=0.472, -0.481 and 0.444, all P<0.001). Conclusion:The T1 and T2 values of rats liver remnant parenchyma showed regular changes, and were correlated with liver regeneration indices, which reflect the microscopic changes of rat liver remnant parenchyma, and are expected to be used for quantitative monitoring of liver remnant regeneration.

2.
Journal of Clinical Hepatology ; (12): 708-713, 2022.
Article in Chinese | WPRIM | ID: wpr-922986

ABSTRACT

Liver failure is a common severe liver disease syndrome in clinical practice and is one of the critical medical conditions in internal medicine. Massive hepatocyte death is the main pathological feature of liver failure, and its core mechanisms include endotoxin, immune response, and inflammatory cascade reaction. Effective regeneration of hepatocytes to compensate liver function is the physiological basis for promoting the good prognosis of liver failure, which directly affects the prognosis and quality of life of patients with liver failure. It has been found in clinical practice that liver failure patients with a low serum level of cholesterol tend to have an extremely high mortality rate, but as an index of hepatocyte anabolism, the association between cholesterol and hepatocyte regeneration has not been taken seriously. Based on the association between cholesterol and liver regeneration, this article reviews its significance and potential value in the clinical treatment of liver failure, in order to understand the pathogenesis of liver failure from another perspective and provide new ideas for the diagnosis and treatment of liver failure and the development of drugs.

3.
Arq. ciências saúde UNIPAR ; 25(3): 225-229, set-out. 2021.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1348215

ABSTRACT

Low-level laser therapy has several biological effects; one of them is tissue regeneration. Recent studies have been held on the application of laser therapy on the liver of rats after partial hepatectomy to promote liver regeneration. The aim of this article was to review the recent studies on the effects of low-level laser therapy on rat liver regeneration after partial hepatectomy and the laser parameters used in those studies. A review of recent relevant literature was performed in Pubmed, Scielo, Medline, and Bireme databases. Articles related to the application of low-level laser therapy on hepatic regeneration were included. Articles with hepatic regeneration in the presence of pathologies were not included. Nine studies were found matching the study criteria. In most studies, low-level laser therapy promoted liver regeneration after partial hepatectomy, without further damage to the remaining liver. Not all laser parameters required for the reproducibility of the study were described by all authors. The therapeutic use of low-level laser therapy in liver regeneration can be promising; however, since the liver is a vital organ, and the laser application is intraoperative, future studies are necessary. The parameters used must be properly described and standardized to allow the reproducibility of the study, in order to define a therapeutic window and thus, consider its clinical use. It is also essential to clarify the mechanisms by which laser promotes liver regeneration to guarantee its safety and therapeutic efficacy.


Laserterapia de baixa potência tem vários efeitos biológicos, sendo um deles a regeneração de tecido. Sua aplicação no fígado de ratos após hepatectomia parcial para promoção de regeneração hepática tem sido estudada recentemente. O objetivo deste artigo foi revisar os estudos recentes dos efeitos da laserterapia de baixa potência na regeneração de fígado de ratos após hepatectomia parcial de fígado e os parâmetros de laser empregados. Uma revisão da literatura relevante recente foi realizada nas bases de dados Pubmed, Scielo, Medline e Bireme. Artigos sobre a aplicação da laserterapia de baixa potência na regeneração de fígado foram incluídos. Artigos sobre regeneração hepática na presença de patologias foram excluídos. Nove estudos foram encontrados correspondendo aos critérios do estudo. Na maioria dos estudos, a laserterapia de baixa potência promoveu regeneração hepática após hepatectomia parcial, sem causar danos adicionais ao fígado remanescente. Não foram descritos todos os parâmetros necessários para reprodutibilidade dos estudos por todos os autores. O uso terapêutico da laserterapia de baixa potência na regeneração de fígado pode ser promissor, entretanto, como o fígado é um órgão vital e a aplicação do laser é intraoperativa, estudos futuros são necessários, assim como os parâmetros da aplicação de laser precisam ser descritos apropriadamente e padronizados, para permitir a reprodutibilidade do estudo, para que uma janela terapêutica possa ser definida e seu uso clínico possa ser considerado. Também é essencial esclarecer através de quais mecanismos o laser promove regeneração de fígado para garantir sua segurança e eficácia terapêutica.

4.
Journal of Clinical Hepatology ; (12): 2706-2709, 2021.
Article in Chinese | WPRIM | ID: wpr-905026

ABSTRACT

China is a big country with liver diseases, and various hepatitis viruses, drug poisons, and alcohol can cause liver injury and even liver failure. The key to the prognosis of patients with liver failure is liver self-repair and regeneration. Alpha-fetoprotein (AFP) has been extensively studied as a tumor marker in liver cancer, but its role in liver regeneration in patients with liver failure awaits further studies. This article summarizes the basic research on AFP in liver regeneration and the clinical research on AFP in acute liver failure and acute-on-chronic liver failure (ACLF), as well as the previous research findings of our group that AFP is an important prognostic index and regeneration factor for liver regeneration after hepatitis B virus-related ACLF. The analysis shows that further studies on the role of AFP in the prognosis of various types of liver failure and the mechanism of liver regeneration will help deepen our understanding of AFP and liver regeneration, thereby providing new ideas and methods for the clinical diagnosis, treatment, and prognostic evaluation of patients with various types of liver failure.

5.
Journal of Clinical Hepatology ; (12): 2696-2700, 2021.
Article in Chinese | WPRIM | ID: wpr-905024

ABSTRACT

Acute-on-chronic liver failure (ACLF) is a life-threatening disease with a high risk of multiple organ failure, sepsis, and death. ACLF activates innate and acquired immune responses in human body and thus leads to the progression of persistent systemic inflammatory response syndrome and multiple organ dysfunction, leading to the high mortality rate of this disease. Dysregulated immune response plays a key role in disease progression, and immunotherapy may help to target immune-mediated organ damage and inhibit the progression of liver failure. This article reviews the role and mechanism of drugs and means with a potential immune regulatory effect in ACLF, in order to provide a reference for immunotherapy for ACLF.

6.
Article in Chinese | WPRIM | ID: wpr-911647

ABSTRACT

Objective:To explore the value of diffusion tension imaging (DTI) in the evaluations of hepatic ischemia-reperfusion injury (WIRI) regulation of liver regeneration after partial hepatectomy.Methods:Thirty healthy adult male New Zealand white rabbits were randomly divided into five groups of control and 10/20/30/40 min warm ischemia time (A0-A4)( n=6 each). Routine magnetic resonance (MR) and diffusion tensor imaging (DTI) were performed at 6 h, 3 d, 7 d, 14 d, 30 d post-keratectomy. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured at Day 30 post-keratectomy. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and proliferating cell nuclear antigen (PCNA) in frozen liver tissues were examined and histopathological examination was performed. The values of apparent diffusion coefficient (ADC), fractional anisotropy (FA) and liver volume were measured and liver regeneration rate (LRR) was calculated. Repeated measurement analysis of variance was employed for comparing the difference of DTI and LRR in different groups at different follow-up times. One-way analysis of variance was utilized for comparing the differences of DTI and LRR between groups at the same follow-up time. Pearson or Spearman correlation analysis was employed for evaluating the correlation between DTI, LRR and biochemical parameters. Results:The interaction between time and warm ischemic factor ( P<0.05) and the effect of both alone ( P<0.001) had statistically significant effects on ADC values. FA value and LRR interaction were not significant between time and warm ischemic factor. However, the dominant effect of time factor was significant ( P<0.05). A significant positive correlation existed between ADC value and LRR in the same warm ischemia group ( P<0.01). FA and LRR were negatively correlated ( P<0.05), except for A3 group. FA had a weak correlation with IL-6 at Day 30 post-operation. Conclusions:DTI can non-invasively and quantitatively evaluate the effect of hepatic WIRI on liver regeneration after partial hepatectomy in rabbits. A certain degree of WIRI (≤30 min) can promote liver regeneration after partial hepatectomy. The longer warm ischemia time, the more obvious promotion effect. However, the promotion effect declines significantly after 30 min.

7.
Article in Chinese | WPRIM | ID: wpr-911579

ABSTRACT

Objective:To investigate the clinical impact factors of liver regeneration after hemihepatectomy in patients with hepatocellular carcinoma (HCC).Methods:Patients who underwent hemihepatectomy due to HCC from Sep 2013 to Sep 2018 were included in the study. Liver volumes were calculated by perioperative simulations to analyze the influencing factors of postoperative liver regeneration, and to compare the albumin bilirubin (ABLI) score and the end-stage liver disease (MELD) score at weeks 1, 5, 9, and 13 after operation.Results:A total of 163 patients were included, of which 13 developed postoperative liver failure. The median liver regeneration rates at 1, 5, 9 and 13 weeks after operation were 22.0%, 32.2%, 33.7% and 35.4%, respectively. Multivariate analysis showed that remnant liver volume (RLV) <611.1 cm 3, %RLV and liver cirrhosis were the influencing factors of liver regeneration. ALBI score and MELD score were lower in the low regeneration group compared to the high regeneration group in the first 5 weeks after operation. Conclusion:RLV and cirrhosis are influential factors in postoperative liver regeneration. Liver regeneration proceeded rapidly within 1 week and slowed down until week 5.

8.
Frontiers of Medicine ; (4): 495-505, 2021.
Article in English | WPRIM | ID: wpr-888737

ABSTRACT

On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of "traditional Chinese medicine (TCM) regulating liver regeneration." A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of "TCM regulating liver regeneration" (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups (P < 0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Hepatitis B/drug therapy , Humans , Liver Failure , Liver Regeneration , Medicine, Chinese Traditional , Retrospective Studies
9.
Journal of Clinical Hepatology ; (12): 857-862, 2021.
Article in Chinese | WPRIM | ID: wpr-875895

ABSTRACT

ObjectiveTo investigate the role of STAT3 in hepatocyte proliferation after acetaminophen (APAP)-induced hepatocellular injury in mice. MethodsNormal mouse AML12 hepatocytes were cultured in vitro and were stimulated by APAP (1, 2.5, 5, 10, and 20 mmol/L) for 12, 24 or 48 hours, and the hepatocytes treated with an equal volume of phosphate buffered saline were established as control group. After the optimal stimulation concentration and duration of action were screened out, AML12 hepatocytes were treated with AG490 (10, 50, and 100 μmol/L). The CCK-8 assay was used to measure the viability of AML12 hepatocytes; RT-PCR was used to measure the mRNA expression levels of PCNA, CyclinD1, and Ki67 in AML12 hepatocytes, and Western blot was used to measure the protein expression levels of STAT3, p-STAT3, PCNA, and CyclinD1. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsAfter 24 and 48 hours of APAP treatment, compared with the control group, all concentration groups had a significant reduction in the viability of AML12 hepatocytes (all P<0.05), with a viability of 0.717±0.0271 and 0.752±0.0141, respectively, when the concentration of APAP was 2.5 mmol/L, which was significantly different from that in the control group (all P<0.05) and met the conditions of subsequent experiment. Compared with the control group, the 24-hour APAP (2.5 mmol/L) group had significant reductions in the mRNA expression of PCNA, CyclinD1, and Ki67 (all P<0.01); compared with the 24-hour APAP group, the 48-hour APAP (2.5 mmol/L) group had significant increases in the mRNA expression of PCNA, CyclinD1, and Ki67 (all P<0.01); therefore, a model of hepatocyte regeneration after in vitro AML12 hepatocyte injury was established by stimulation with APAP 2.5 mmol/L for 48 hours. After the addition of AG490, there was no significant difference in viability between the control group and the 10 and 50 μmol/L AG490 groups, and the other groups had a significant reduction in viability (all P<0.01); compared with the APAP group, the AG490 (50 μmol/L)+APAP group and the AG490 (100 μmol/L)+APAP group had a significant reduction in viability (P<0.01); therefore, 50 μmol/L AG490 was selected as the concentration for subsequent experiment. Compared with the control group, the APAP group had a significant increase in the protein expression level of p-STAT3 (P<0.01), while the AG490 group and the APAP+AG490 group had a significant reduction (both P<0.05); compared with the APAP group, the APAP+AG490 group had significant reductions in the protein expression levels of PCNA and CyclinD1 and the mRNA expression levels of PCNA, CyclinD1, and Ki67 (all P<0.05). ConclusionSTAT3 participates in hepatocyte proliferation after APAP-induced hepatocyte injury in mice, while AG490, as an STAT3 inhibitor, can inhibit hepatocyte proliferation after APAP-induced hepatocyte injury by inhibiting the phosphorylation of STAT3.

10.
Journal of Clinical Hepatology ; (12): 480-484, 2021.
Article in Chinese | WPRIM | ID: wpr-873426

ABSTRACT

Liver failure is a common critical medical disease, and extensive liver cell necrosis within a short period of time exceeds the regeneration capacity of liver cells and thus results in an extremely high fatality rate. Promotion of effective liver regeneration is the key to antagonizing liver failure. Recent studies have shown that bile acid, farnesoid X receptor (FXR), and intestinal microecology play an important role in liver failure and liver regeneration. This article reviews the association between bile acid, FXR, and intestinal microecology and their role in liver failure and liver regeneration, so as to provide new ideas for the treatment of liver failure in clinical practice.

11.
Rev. Col. Bras. Cir ; 48: e20213164, 2021. tab, graf
Article in English | LILACS | ID: biblio-1351520

ABSTRACT

ABSTRACT Objective: to evaluate the influence of acetylsalicylic acid (ASA) on cell proliferation after partial hepatectomy in rats. Methods: 40 male Wistar rats were separated into four groups of ten rats each. Groups 1 and 2 (controls): undergoing 30% partial hepatectomy and, after one day (group 1) and seven days (group 2), to euthanasia; daily administration of 0.9% saline solution (1mL per 200g of body weight). Groups 3 and 4 (experimental): undergoing 30% partial hepatectomy and, after one day (group 3) and seven days (group 4), to euthanasia; daily administration of ASA (40mg/mL, 1mL per 200g of body weight). The absolute number of cells stained with PCNA was counted in photomicrographs, in five fields, and it was calculated the mean of positive cells per animal and per group. Results: the final mean of PCNA+ cells per group was: in group 1, 17.57 ± 6.77; in group 2, 19.31 ± 5.30; in group 3, 27.46 ± 11.55; and, in group 4, 12.40 ± 5.23. There was no significant difference at the two evaluation times in the control group (p=0.491), but there was in the experimental group (p=0.020), with a lower number of PCNA+ cells on the seventh day. The comparison between the two groups, on the first day, showed more PCNA+ cells in the livers of the animals that received ASA (p=0.047), and on the seventh day the number was lower in the experimental group (p=0.007). Conclusion: ASA induced greater hepatocyte proliferation.


RESUMO Objetivo: avaliar a influência do ácido acetilsalicílico (AAS) na proliferação celular após hepatectomia parcial em ratos. Métodos: 40 ratos Wistar machos foram separados em quatro grupos com dez ratos cada. Grupos 1 e 2 (controles): submetidos à hepatectomia parcial de 30% e, após um (grupo 1) e sete dias (grupo 2), à eutanásia; administração diária de solução fisiológica 0,9% (1mL por 200g de peso). Grupos 3 e 4 (experimentos): submetidos à hepatectomia parcial de 30% e, após um (grupo 3) e sete dias (grupo 4), à eutanásia; administração diária de AAS (40mg/mL, 1mL por 200g de peso). Realizou-se a contagem do número absoluto de células coradas com PCNA em fotomicrografias, em cinco campos e cálculo da média de células positivas por animal e por grupo. Resultados: A média final de células PCNA+ por grupo foi: no grupo 1, de 17,57 ± 6,77; no grupo 2 de 19,31 ± 5,30; no grupo 3, de 27,46 ± 11,55; e, no grupo 4, de 12,40 ± 5,23. Não houve diferença significante nos dois tempos de avaliação no grupo controle (p=0,491), mas houve no grupo experimento (p=0,020), observando-se menor número de células PCNA+ no sétimo dia. A comparação entre os dois grupos, no primeiro dia, mostrou mais células PCNA+ nos fígados dos animais que receberam AAS (p=0,047), e no sétimo dia o número foi menor no grupo experimento (p=0,007). Conclusão: O AAS induziu maior proliferação hepatocitária.


Subject(s)
Animals , Male , Rats , Aspirin , Liver Regeneration , Rats, Wistar , Hepatectomy , Liver
12.
Acta Pharmaceutica Sinica B ; (6): 727-737, 2021.
Article in English | WPRIM | ID: wpr-881165

ABSTRACT

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

13.
Article in Chinese | WPRIM | ID: wpr-910591

ABSTRACT

Liver sinusoidal endothelial cells (LSECs) play a positive role in maintaining microcirculation of the liver to achieve liver homeostasis, and they also mediate a balance between regeneration and fibrosis in the process repair of liver injury. After acute liver injury, LSECs are the regulators of liver regeneration, while in chronic injury, abnormally activated LSECs promote development of liver fibrosis. In this paper, we summarized the recent progress in research on the balance between LSECs-mediated liver regeneration and fibrosis, with the aim to provide new ideas in treating liver fibrosis and promoting liver regeneration by targeting LSECs.

14.
Acta Pharmaceutica Sinica B ; (6): 3791-3805, 2021.
Article in English | WPRIM | ID: wpr-922441

ABSTRACT

Acetaminophen (APAP) overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States. We investigated the role of p62/SQSTM1 (referred to as p62) in APAP-induced liver injury (AILI) in mice. We found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment, which was inversely correlated with the hepatic levels of APAP-adducts. APAP also activated mTOR at 24 h, which is associated with increased cell proliferation. In contrast, p62 knockout (KO) mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP treatment. Surprisingly, p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 h. We found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor (VWF) and platelet aggregation, which are associated with increased cell proliferation and improved liver injury at 48 h after APAP treatment. Our data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.

15.
Journal of Clinical Hepatology ; (12): 2344-2348, 2020.
Article in Chinese | WPRIM | ID: wpr-829415

ABSTRACT

Insufficient volume of future liver remnant (FLR) often leads to the complications including liver failure and even death and thus remains a bottleneck for liver surgery. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a newly developed two-stage hepatectomy procedure which can promote rapid regeneration of FLR, but the related mechanism has not yet been elucidated. With reference to the recent research advances in China and foreign countries, this article reviews the hemodynamic and humoral factors for ALPPS in promoting liver regeneration, the effect of ALPPS on liver parenchymal cells, and the role of non-parenchymal liver cells (including hepatic stellate cells, natural killer cells, macrophages, and liver progenitor/stem cells) in regulating liver regeneration. It is pointed out that the interaction between non-parenchymal liver cells and parenchymal cells is a hotspot in the research on the mechanism of liver regeneration after ALPPS.

16.
Acta Pharmaceutica Sinica ; (12): 2243-2255, 2020.
Article in Chinese | WPRIM | ID: wpr-829371

ABSTRACT

Liver fibrosis is a critical pathological structural basis of a variety of chronic liver diseases such as alcoholic liver disease, viral hepatitis and nodular cirrhosis, while liver regeneration is the key mechanism for protecting liver against multiple injuries, promoting inflammation resolution and reversing liver fibrosis. When fibrosis occurs after liver injuries, the alternation of liver regeneration status in fibrosis usually plays an essential role in the outcome of diverse liver diseases. In this review, the differences between "homeostatic regeneration", "normal regeneration" and "aberrant regeneration" were identified in terms of the occurrence conditions, the basic state of the liver, the effects on liver repair, the types of cells involved and the pathogenesis. Emphatically, we not only summarize the differences of mechanisms between "aberrant regeneration" and "normal regeneration" in the pathogenesis of liver fibrosis, but also elucidate the features of "aberrant regeneration" in various liver fibrosis models, as well as the therapeutic strategies for the treatment of liver fibrosis based on "aberrant regeneration", expecting to provide evidence and clues for considering the risks and proposing possible solutions in clinical treatment of liver fibrosis.

17.
Article in Chinese | WPRIM | ID: wpr-847351

ABSTRACT

BACKGROUND: Liver transplantation is the standard treatment for end-stage liver disease and liver failure. However, ischemia-reperfusion injury can reduce the success rate of liver transplantation. When a limited number of liver donors are available for transplantation, how to reduce liver ischemia-reperfusion injury has become the primary issue in liver transplantation. OBJECTIVE: To evaluate the effect of macrolide antibiotics on ischemia-reperfusion injury after liver transplantation in rats. METHODS: Rat autologous orthotopic liver transplantation model was constructed. Wistar rats were randomly divided into macrolide antibiotics group and control group. In the macrolide antibiotics group, the donor liver was treated with macrolide antibiotics (60 mg/kg roxithromycin, 20 mg/kg clarithromycin and 40 mg/kg erythromycin) 30 minutes before hepatectomy, and the above macrolide antibiotic mixture was injected into the portal vein immediately after orthotopic liver transplantation. In the control group, rats were pretreated with the same volume of saline for 30 minutes before hepatectomy, and the same volume of saline was injected into the portal vein immediately after orthotopic liver transplantation. The survival rate of the rats was observed within 7 days after liver transplantation. The serum aspartate aminotransferase and alanine aminotransferase activities were detected by automatic biochemical analyzer at 48 and 72 hours after liver transplantation. Hematoxylin-eosin staining and immunohistochemistry assay were used to detect the morphological changes of liver tissues and the number of Ki-67 positive cells in liver transplantation rats. TUNEL and western blot assay were used to detect the number of apoptotic hepatocytes and the expression of caspase-3 and cleaved caspase-3 proteins in liver transplantation rats, respectively. The Kupffer cell number changes and levels of interleukin-6, interleukin-1β, and tumor necrosis factor-α in rat liver tissues after liver transplantation were detected by immunofluorescence and ELISA, respectively. RESULTS AND CONCLUSION: Macrolide antibiotics increased the overall survival rate of liver transplanted rats, improved the dysfunction of transplanted liver, reduced the severity of ischemia-reperfusion injury after liver transplantation, increased the regenerative capacity of transplanted liver, reduced the number of apoptotic cells and the ratio of cleaved caspase-3/caspase-3 in the transplanted liver tissue, and decreased the number of Kupffer cells and the levels of interleukin-6, interleukin-1β and tumor necrosis factor-α in the transplanted liver. All the results indicate that macrolide antibiotics protect against ischemia-reperfusion injury in rats undergoing liver transplantation.

18.
Journal of Clinical Hepatology ; (12): 1896-1899, 2020.
Article in Chinese | WPRIM | ID: wpr-825053

ABSTRACT

Liver regeneration is an important response after liver injury and necrosis to maintain liver volume and function, with the involvement of various factors and signaling pathways. This process has three main stages, i.e., the initial stage of mitosis triggered by certain factors, the proliferation stage of promoting hepatocytes to enter the cell cycle, and the termination stage of promoting liver cells to reach a certain number and the recovery of liver mass. This article introduces various factors and multiple cellular signaling pathways that promote the differentiation of liver stem cells into liver cells to restore liver volume and function and summarizes the previous research findings of our group that alpha-fetoprotein is an important serum marker for liver regeneration after liver failure. The analysis shows that in-depth studies of the occurrence and clinical application of liver regeneration will help to improve the understanding of liver regeneration, better predict the prognosis of acute and chronic liver diseases, and provide new ideas and methods for the clinical diagnosis and treatment of various advanced liver diseases.

19.
Journal of Clinical Hepatology ; (12): 1666-1668, 2020.
Article in Chinese | WPRIM | ID: wpr-822916

ABSTRACT

microRNAs (miRNAs) are low-molecular-weight non-coding RNAs that regulate various physiological and pathological functions through the regulation of gene expression at the post-transcriptional level. More and more evidence has shown that microRNA-27a (miRNA-27a) plays a role in the development and pathogenesis of liver diseases. By reviewing and updating related studies, this article introduces the research advances in the role of miRNA-27a in various liver diseases including fatty liver disease, hepatitis, hepatic fibrosis, and liver cancer and analyzes the role of miRNA-27a in liver regeneration and its potential as a biomarker, so as to provide a reference for future studies and more possibilities for new treatment ideas for chronic hepatic diseases.

20.
Acta cir. bras ; 34(11): e201901103, Nov. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054680

ABSTRACT

Abstract Purpose: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. Methods: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. Results: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. Conclusion: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.


Subject(s)
Animals , Male , Portal Vein/surgery , Hepatic Artery/surgery , Liver/diagnostic imaging , Liver Regeneration/physiology , Organ Size/physiology , Immunohistochemistry , Random Allocation , Tomography, X-Ray Computed/methods , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Imaging, Three-Dimensional/methods , Hepatomegaly/physiopathology , Hepatomegaly/diagnostic imaging , Ligation , Liver/blood supply , Liver/pathology
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