scholarly journals Portal Modulation Effects of Terlipressin on Liver Regeneration and Survival in a Porcine Model Subjected to 90% Hepatectomy

Author(s):  
Hye-sung Jo ◽  
Hyun-Jin Park ◽  
Yoon Young Choi ◽  
Jin-I Seok ◽  
Jae-Hyun Han ◽  
...  

Abstract BackgroundExcessive postoperative portal pressure is associated with post-hepatectomy liver failure and small-for-size syndrome after partial liver transplantation. This study aimed to identify the portal modulation effects of terlipressin on liver regeneration and survival in a porcine model subjected to 90% hepatectomy.MethodsTwenty pigs undergoing 90% hepatectomy were divided into control (n=10) and terlipressin (n=10) groups. Terlipressin 0.5 mg was injected subcutaneously three times a day, from immediately before hepatectomy to 7 days after surgery, for surviving pigs in the terlipressin group. Portal pressure measurement, biochemical analysis, assessment of molecular markers for liver regeneration, and immunohistochemistry were performed in both groups. ResultsThe 7-day survival rate was significantly higher in the terlipressin group than in the control group. Portal pressure in the terlipressin group was lower than that in the control group at 30 min and 1 h after hepatectomy. Total bilirubin level was lower in the terlipressin group than in the control group at 1 h and 6 h after hepatectomy. Proliferating cell nuclear antigen expression was higher in the control group than in the terlipressin group at 6 h after hepatectomy, while the proportion of Ki-67-positive cells was higher in the terlipressin group than in the control group at 7 days after hepatectomy. Endothelin-1 levels reflecting liver injury were lower in the terlipressin group than in the control group at 1 h and 6 h after hepatectomy.ConclusionTerlipressin could optimize liver regeneration and improve survival through rapid and effective portal modulation after extensive hepatectomy.

HPB Surgery ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
R. Ladurner ◽  
M. Schenk ◽  
R. Margreiter ◽  
F. Offner ◽  
A. Königsrainer

Objective. The minimal amount of liver mass necessary for regeneration is still a matter of debate. The aim of the study was to analyze liver regeneration factors after extended resection with or without portosystemic shunt. Methods. An extended left hemihepatectomy was performed in 25 domestic pigs, in 15 cases after a portosystemic H-shunt. The expression of Ki-67, VEGF, TGF-, FGF, and CK-7 was analyzed in paraffin-embedded tissue sections. Results. The volume of the remnant liver increased about 2.5-fold at the end of the first week after resection. With 19 cells/10 Glisson fields versus 4/10, Ki-67-expression was significantly higher in the H-shunt group. VEGF- and CK-7-expressions were significantly higher in the control group. No significant change was found in FGF-expression. The expression of TGF- was higher, but not significantly, in the control group. Conclusions. The expression of Ki-67, and therefore hepatocyte regeneration, was increased in the shunt group. The expression of CK-7 on biliary epithelium and the expression of VEGF, however, were stronger in the control group.


2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094379
Author(s):  
Yanshan Li ◽  
Yunxiuxiu Xu ◽  
Ruomei Wang ◽  
Wenxin Li ◽  
Wenguang He ◽  
...  

Objective To investigate whether the Notch–Hif-1α signaling pathway is involved in liver regeneration. Methods Rats were divided into two groups and treated with daily intraperitoneal injections of saline (control) or the gamma-secretase inhibitor, Fli-06, for 2 days. Two-thirds of the rat livers were resected and rats were later euthanized at specific time points post-resection to analyze the remnant livers. Each group's liver/body weight ratio was calculated, and immunostaining and western blotting were used to determine the cell proliferation marker, PCNA and Ki-67 expression. Real-time PCR and western blotting were used to compare the mRNA expression of Notch homolog-1 ( Notch1), hairy and enhancer of split-1 ( Hes1), and vascular endothelial growth factor ( Vegf), and the protein expression of NICD and HIF-1α, respectively. Results The liver/body weight ratios and number of Ki-67- and PCNA-positive cells were significantly lower in the experimental group than the control group, indicating lower levels of liver regeneration following the disruption of Notch signaling by Fli-06. The Hes1 and Vegf mRNA levels and NICD and HIF-1α protein expression levels were all down-regulated by Fli-06 treatment. Conclusion Notch–Hif-α signaling pathway activation plays an important role in liver regeneration, where it may contribute toward liver cell proliferation.


2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 37-39 ◽  
Author(s):  
Renata Lemos Silva ◽  
Gustavo Barreto de Melo ◽  
Valdinaldo Aragão de Melo ◽  
Ângelo Roberto Antoniolli ◽  
Paulo Roberto Teixeira Michellone ◽  
...  

PURPOSE: The use of medicinal plants for the treatment of human diseases has increased worldwide. Many of them are used by oral administration and, after absorption, may affect many organs. Therefore, this study aimed at assessing the effects of the aqueous extract of Sida cordifolia leaves, popularly known in Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were divided into four groups: control, Sida100, Sida200 and Sida400 groups. All animals were submitted to oral administration of distilled water, 100, 200 and 400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately after this, they underwent 67% partial hepatectomy. Twenty four hours later, their livers were removed. Hepatic regeneration was assessed by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed higher liver regeneration indices than control group (p<0.001 and p<0.05, respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates liver regeneration after 67% partial hepatectomy in rats.


2014 ◽  
Vol 41 (3) ◽  
pp. 203-207 ◽  
Author(s):  
Edimar Leandro Toderke ◽  
Giorgio Alfredo Pedroso Baretta ◽  
Ozimo Pereira Gama Filho ◽  
Jorge Eduardo Fouto Matias

OBJECTIVE: To evaluate the influence of sirolimus on liver regeneration triggered by resection of 70% of the liver of adult rats. METHODS: we used 40 Wistar rats randomly divided into two groups (study and control), each group was divided into two equal subgroups according to the day of death (24 hours and seven days). Sirolimus was administered at a dose of 1mg/kg in the study group and the control group was given 1 ml of saline. The solutions were administered daily since three days before hepatectomy till the rats death to removal of the regenerated liver, conducted in 24 hours or 7 days after hepatectomy. Liver regeneration was measured by the KWON formula, by thenumber of mitotic figures (hematoxylin-eosin staining) and by the immunohistochemical markers PCNA and Ki-67. RESULTS: there was a statistically significant difference between the 24h and the 7d groups. When comparing the study and control groups in the same period, there was a statistically significant variation only for Ki-67, in which there were increased numbers of hepatocytes in cell multiplication in the 7d study group compared with the 7d control group (p = 0.04). CONCLUSION: there was no negative influence of sirolimus in liver regeneration and there was a positive partial effect at immunohistochemistry with Ki-67.


1987 ◽  
Vol 133 (3) ◽  
pp. 579-584 ◽  
Author(s):  
Kohsuke Sasaki ◽  
Tomoyuki Murakami ◽  
Masahiro Kawasaki ◽  
Manabu Takahashi

2021 ◽  
pp. 34-39
Author(s):  
T.V. Mielikhova ◽  
O.V. Gryshchenko ◽  
V.V. Lazurenko ◽  
R.A. Safonov ◽  
O.S. Alekseeva

Study objective: to optimize diagnostic measures in patients with adenomyosis and/or hyperplastic endometrial processes (HEP).Material and methods. The study included 128 patients aged from 27 to 53 years. The first group included 38 (29.6%) patients with a grade I–II adenomyosis, the second group included 41 (32.1%) patients with a combination of grade I–II adenomyosis and HEP and/or uterine leiomyoma, the third group included 39 (30.5%) women with only HEP, the fourth (control) group included 10 (7,8%) women without endometrial pathology. Patients underwent hysteroscopy with targeted biopsy, elucidated the pathomorphological features of connective tissue component of the endometrium and uterus transitional zone, studied specific markers of adenomyosis progression, namely vascular endothelial growth factor and Ki-67 proliferation index, and also determined the parameters of shear wave ultrasound elastography.Results. Routine histological examination of adenomyosis was confirmed only in 11 (30.6%) cases out of 36 suspected, while HEP (polyps, glandular hyperplasia) and hyperplastic pathology of endocervix (polyps) – in 34 (97.1%) cases out of 35 suspected. Ki-67 antigen expression was positive in the nuclei of epithelial cells in the adenomyosis glands and in the cytogenic stroma cells. A greater value of expression was in the epithelium of glands in superficially located heterotopies – with grade I–II adenomyosis compared with other studied groups. Shear wave elastography showed significant differences in the myometrium color between the first, third and control groups. The unchanged myometrium in all patients of the control group was characterized by staining in shades of blue, while in 9 (90%) patients the color was uniform.Conclusion. It is recommended to use a shear wave ultrasound elastography in laboratory and instrumental examination with determination of Ki-67 proliferation protein expression and intensification of the neovascularization process in endometrial biopsy specimens to improve the diagnosis of adenomyosis.


2020 ◽  
Vol 21 (15) ◽  
pp. 5457
Author(s):  
Sophia M. Schmitz ◽  
Henriette Dohmeier ◽  
Christian Stoppe ◽  
Patrick H. Alizai ◽  
Sandra Schipper ◽  
...  

Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1β, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1β and IL-6 was significantly higher after argon inhalation after 36 h (IL-1β 5.0 vs. 8.7 fold, p = 0.001; IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1β and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.


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