Liver Resection In Rats Research Articles

Hemostatic effects of traditional Inula viscosa and Capsella bursa-pastoris plant mixture extract on rat liver parenchymal bleeding model.

Failure to achieve effective bleeding control and problems related to transfusion in liver surgery are the most common causes of post-operative mortality and morbidity. Various methods/drugs including topical hemostatic agents have been em-ployed for bleeding control in liver surgery. This study was aimed to investigate the hemostatic properties of the herb mixture extract of Inula viscosa and Capsella bursa-pastoris (IvCbp) in rat liver laceration model, which have been traditionally used as antiseptic and hemostatic agents public in Hatay/Tukey. Thirty rats were divided into three groups equally and blood samples were taken from all rats for preoperative hemoglobin (Hb) measurements. Then, the standard liver resection model was applied to all rats. Sponge for the first rat group, Ankaferd Blood Stopper® Trend-Tech for the second rat group and IvCbp plant extract mixture for the third group were applied to resection areas for 3 minutes. Liver samples of all rats were evaluated in terms of inflammation and necrosis intensity on the 5th post-operative day. Post-operative Hb values were found as 11.0±1.1 g/dL in the sponge group, 11.9±2.0 g/dL in the Ankaferd group, and 14.1±1.2 g/dL in the IvCbp herb mixture group (p<0.001). In the histopathological examination, less necrosis was observed in the herb mixture group compared to the sponge and Ankaferd groups (p=0.001). In addition, no statistically significant necrosis difference was observed between sponge and Ankaferd groups. While less inflammation was observed in the herb mixture group compared to the other groups, Ankaferd group had the highest inflammation score (p<0.001). IvCbp herb mixture extract group provide effective hemostatic control, caused less Hb decrease and resulted in less inflammation and necrosis compared to Ankaferd and sponge groups in a rat liver resection model.

The Early Changes in Splenic Lymphocyte and Macrophage Populations Following Major Liver Resection in Rats.

Background and aim of the work: Splenic hypertrophy occur after major hepatectomy (HTX). The spleen was suggested to inhibit hepatocyte proliferation and consequently, splenectomy was considered. The present study aims to examine the influence of 70% partial hepatectomy (HTX) on the splenic histological structure, T, B lymphocyte and macrophage populations and to discuss the functional correlation.Methods: The rats were assigned to two groups; Sham group, and 70% Partial hepatectomy (HTX) group; which was further subdivided into 2 subgroups; sacrificed 24 or 48h, after HTX; Groups (HTX 24h) and (HTX 48h); respectively. H & E as a routine stain, iron staining by Prussian blue, as well as immunohistochemical detection of splenic CD3; a marker for T lymphocyte; CD20; a marker for B lymphocyte and CD68; a marker for macrophage; were done.Results: HTX 24h and HTX 48h groups exhibited enlargement of splenic follicles, no expansion of red pulp , no increase in apoptosis, mild increase in the number of melanomacrophages. CD3 expression increased significantly in HTX groups as compared to Sham group. However, CD3 expression in HTX 24h and HTX 48h groups exhibited insignificant difference. CD20 expression showed no significant difference among the studied groups. CD68 expression and Prussian blue staining showed a non-significant increase in HTX 24h group and significant increase in HTX 48h group.Conclusion: During the first two days after HTX, there was a rapid increase in splenic T- but not B-lymphocytes with subsequent increase in splenic macrophages. The splenic changes may explain a role of in liver regeneration.

Hemostatic performance of chitosan-based hydrogel and its study on biodistribution and biodegradability in rats

Hemostasis is of great significance regardless of the smooth operation or postoperative recovery. Therefore, it is urgent to develop a hemostatic material with excellent biodegradability and biocompatibility. It is well known that both carboxymethyl chitosan and hyaluronic acid with biodegradability and biocompatibility have wound healing promoting property. Here, a degradable chitosan-based hydrogel was prepared based on carboxymethyl chitosan and cross-linked by oxidized hyaluronic acid. The hemostatic performance of the hydrogel in rat liver resection injury was evaluated which results showed that the hydrogel exhibited comparable hemostatic properties compared with Fibrin Sealant. In addition, the hydrogel proved to be rapidly absorbed by the body without significant accumulation in vivo, demonstrating good biodegradability and biocompatibility. The overall results suggested the hydrogel will be a promising hemostatic hydrogel for controlling bleeding.

Efficacy of New Polylactic Acid Nonwoven Fabric as a Hemostatic Agent in a Rat Liver Resection Model.

During minimally invasive surgery, efficient and nontoxic hemostats are important for difficult to access bleeding areas. Polylactic acid is an ecofriendly hemostatic agent and we aimed to evaluate the efficacy of a polylactic acid nonwoven fabric (PLAF) developed by Toray Industries, Inc, on liver hemostasis in a preclinical study. PLAF consists of both 1-µm diameter fibers and 100-µm diameter beaded fibers. Four rats were used, and 2 trough-shaped resections of the liver parenchyma were performed (n = 8 lobes). Immediately after the resection, PLAF (PLAF group: n = 4 lobes) or rayon gauze (Rayon group: n = 4 lobes) were applied on the resected plane and compressed manually. We compared the mean time to hemostasis and blood loss per lobe, as well as histological findings between the groups. The PLAF group had a significantly shorter bleeding time ( P = .006), and showed lower blood loss compared with the Rayon group ( P = .076). Histopathological evaluation showed a large amount of beads on the liver surface in the PLAF group. Aggregated red blood cells evident by electron microscopy and von Willebrand factor immunofluorescence were seen surrounding the beads. The PLAF group showed significantly greater von Willebrand factor expression than the Rayon group ( P = .004). This new PLAF showed superior outcomes thanks to its unique characteristic of forming beaded nanofibers, and it has the potential to be an efficient hemostat in minimally invasive surgery in the human body.

Изучение хоуминга ммск после резекции печени

Цель работы - изучение направленного движения мультипотентных мезенхимальных стромальных клеток (ММСК), выделенных из плаценты, в различные органы и ткани лабораторных животных в физиологических условиях и после субтотальной резекции печени. Методика. Клеточную культуру ММСК получали из хориона плаценты лабораторных крыс. Культивирование ММСК проводилось в условиях СО2- инкубатора при температуре 37 ºC с содержанием углекислого газа 5% и влажностью 90%. Замену среды проводили каждые 3-4 сут до достижения клетками 70-80 % конфлюэнтности. При формировании соответствующего монослоя осуществлялся пересев клеток. При трансплантации лабораторным животным была использована культура ММСК 3-го пассажа. Введение клеток производили сразу после выполнения субтотальной резекции печени. Резекция 70% печени у крыс выполнена по методике G.M. Higgins, R.M. Anderson. Введение ММСК, меченых акридиновым оранжевым, осуществляли внутривенно, интраперитонеально, в печеночную артерию, в портальную вену в дозе 4 млн кл/кг. массы тела. Анализ распределения ММСК проводили через 3 и 24 ч. Результаты. Показано, что через 1 сут после введения клеток ложно-оперированным животным не отмечено существенных изменений распределения ММСК по сравнению с их распределением через 3 ч. Однако если введение клеток сопряжено с оперативным вмешательством (лапаротомия для обеспечения введения клеток в v. portae и a. hepatica) происходит снижение их количества в периферической крови. Через 1 сут после резекции печени в изучаемых органах и тканях (периферическая кровь, легкое, селезенка, костный мозг, тонкий кишечник, почка) содержание трансплантированных ММСК ниже по сравнению с их количеством в тот же период времени в данных органах и тканях без резекции печени. Обращает внимание значительное увеличение количества введенных клеток в печени после ее резекции как через 3 ч, так и через 24 ч по сравнению с физиологическими условиями. Заключение. Отмечено значительное увеличение количества клеток в печени после ее резекции вне зависимости от способа введения. Внутрибрюшинный способ введения клеток показал низкую эффективность доставки клеток в органы и ткани организма. The aim was to study migration of multipotent mesenchymal stromal cells (MSCS) isolated from the placenta to various organs and tissues of laboratory animals under the physiological conditions and after subtotal liver resection. Method. The MMSC cells for culturing were obtained from the rat placental chorion. MMSCs were cultured in a CO2 incubator at 37 oC, 5% CO2, and 90% humidity. The medium was replaced every 3-4 days until the cells reached 70-80 % confluence. Upon formation of an appropriate monolayer the cells were passed. The third passage culture of MMSC was used for transplantation to laboratory animals. Cells were injected immediately after subtotal liver resection. The 70% rat liver resection was performed according to the method of G.M. Higgins and R.M. Anderson. The acridine orange labeled MMSC were injected intravenously, intraperitoneally, into the hepatic artery, and into the portal vein at a dose of 4x106 cells/kg body weight. The MMSC distribution was analyzed at 3 and 24 hours. Results. In 24 h after the cell injection in the absence of liver resection, no significant changes were observed in the MMSCs distribution compared to their distribution in 3 hours. However, when the cell injection was associated with a surgery (laparotomy to ensure the cell injection into the portal vein and hepatic artery) the cell number was decreased in the peripheral blood. At one day after liver resection, the content of transplanted MMSCs was lower in the studied organs and tissues (peripheral blood, lung, spleen, bone marrow, small intestine, and kidney) compared to the respective values without liver resection in the same period. Noticeably, the number of injected cells was significantly increased in the liver at both 3 and 24 hours after resection compared to the physiological conditions. Conclusion. The number of cells was significantly increased in the liver after resection regardless of the cell administration route. Intraperitoneal cell injection showed a low effectiveness of cell delivery to organs and tissues.

Regulation of hepatocyte proliferation after subtotal liver resection in rats

Hepatocyte proliferation is the main cellular mechanism of liver regeneration. However, after removal of more than 80 % of the liver mass, a temporary block of hepatocyte proliferation is observed, which may be the cause of impaired regeneration during transplantation and liver resection in the clinical practice. The current study aims to analyze the molecular mechanisms of hepatocyte proliferation impairment after subtotal liver resection in rats. In male Wistar rats, a model of liver regeneration after subtotal resection is reproduced - removal of more than 80 % of liver mass. Using the methods of immunohistochemistry, PCR-RT, western blot, possible molecular mechanisms of slowing down the proliferation of hepatocytes were studied. It was found that expression of cyclin D1 and E increased only 30 hours after surgery. Their appearance coincides with the beginning of transcription of genes for Cyclins D1 and E1 at 30 h after surgery. The corresponding increase in concentrations of cyclin D, and E proteins is further delayed till 48 h after surgery. These results indicate that, in this particular model, hepatocytes are reluctant to undergo transition between G0- and G1 -phases of cell cycle. We have observed a prolonged decrease in the expression of protooncogene C-met (the hepatocyte growth factor receptor-encoding gene Met). We have also observed an increase in expression of the transforming growth factor beta-1 receptor-encoding gene TgfbrII. At the same time, irreversible block of hepatocyte proliferation was prevented by expression of certain factors, notably of the TWEAK/ Fn14 signaling pathway: concentrations of the corresponding proteins in remnant livers have peaked from 24 h to 48 h after surgery. Thus, after subtotal liver resection, the remaining hepatocytes are exposed to a large scope of both mitogenic and antimitogenic factors. Proliferative behavior of hepatocytes in remnant livers is determined by fine balance of these factors. The prevalence of antimitogenic factors in the early period after surgery delays the onset of hepatocyte proliferation.

Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis.

The aim of the present study was to investigate the effects of hepatic blood inflow on liver function, liver ultrastructure and the regeneration of future liver remnant (FLR) following major hepatectomy in rats with liver cirrhosis. A rat model of cirrhosis was established through intraperitoneal injection of carbon tetrachloride for 8 consecutive weeks. Extensive liver resection and different blood inflow models by portal vein (PV) and/or hepatic artery (HA) stenosis were conducted on the cirrhosis rats. Animal models were constructed as follows: Control (group A), low-flow PV + high-flow HA (group B), low-flow PV + low-flow HA (group C), high-flow PV + high-flow HA (group D) and high-flow PV + low-flow HA (group E). Hepatic blood inflow was detected by laser speckle contrast analysis, liver function and pathological changes were analyzed, Masson staining was used to identify the fibrosis of the liver and Periodic acid-Schiff staining was used to identify glycogen synthesis and hepatocyte function. The liver cell ultrastructure was evaluated by transmission electron microscopy, and the expression of Ki-67 in hepatocytes and the weight of the FLR were recorded to determine the regeneration of the FLR. Five days after major hepatectomy and liver blood inflow modulation, pathological examination of the livers from groups B and C revealed less congestion and less extensive hepatocellular injury. The serum alanine aminotransferase level of group B at 1, 3 and 5 days after hepatectomy and blood inflow modulation was 460.9±31.7, 331.0±22.0 and 285.6±15.8 U/l, respectively (control group: 676.9±41.7, 574.9±28.0 and 436.1±32.7 U/l, respectively; P<0.05); the total bilirubin of group B at 1, 3 and 5 days was 20.4±1.5, 16.1±1.0 and 13.5±0.6 µmol/l, respectively (control group: 30.3±1.4, 26.5±0.8 and 22.1±1.2 µmol/l, respectively; P<0.05). The size of the endoplasmic reticulum in the low-flow PV groups increased significantly and the mitochondrial swelling was alleviated. The positive rate of Ki-67 in the hepatocytes of groups B, C and D was 23.9±3.6, 15.7±2.3 and 12.9±2.4%, respectively (control group: 10.1±2.1%, P<0.05), and the positive rate of Ki-67 in group E was 6.1±1.4% (compared with that of the control group, P<0.05). The remnant liver weight of group B was 15.4±1.0 g (compared with that of the control group, P<0.05). Therefore, decreased portal blood flow combined with increased hepatic arterial blood flow alleviated the congestion in the liver following major hepatectomy in cirrhotic rats, improved the pathological status and liver function, increased the expression of Ki-67 and promoted liver regeneration.

The many ways to mend your liver: A critical appraisal.

In the latter half of the 20th century, our understanding of mammalian liver regeneration was shaped by the manner of compensatory hyperplasia occurring after a partial rat liver resection. This response involves almost all hepatocytes and thus is unlikely to be the outcome of the multiple cycling of a small stem cell population. It was most intense in the outer third of lobule, the location closest to the afferent arterial blood supply. With the advent of heritable genetic labelling techniques, usually applied to mice, hitherto unrecognized hepatocytes with clonogenic potential have been discovered, contributing to homoeostatic renewal and/or regenerative responses after tissue loss. This review combines observations from cell lineage tracing studies with other data to summarize the Four proposed anatomical locations for hepatocyte stem cells: the periportal zone, the pericentral zone, a randomized distribution and finally within the intrahepatic biliary tree. As in other endodermal-derived tissues, it appears that there are both homoeostatic stem cells and regenerative stem cells, while some normally homoeostatic stem cells can become more active to boost regeneration.

Multipotent stromal cells stimulate liver regeneration by influencing the macrophage polarization in rat

AIMTo investigate the influence of the umbilical cord-derived multipotent stromal cells (MSCs) on recovery of the liver after the subtotal resection, that is, removal of 80% of the organ mass, a renowned model of the small-for-size liver remnant syndrome.METHODSThe MSCs were obtained from the intervascular tissue of umbilical cords, dissected from rat fetuses, by the explant culture technique. The vital labeling of MSCs with РКН26 was carried out on the 3rd passage. The subtotal resection was performed on male Sprague-Dawley rats. The experimental group animals received a transplant 106 MSCs infused into the spleen. Hepatocyte proliferation was assessed by counting of either mitotic figures or Ki67-positive cells in microscopic images. MSC differentiation was assessed with antibodies to hepatocyte-specific marker cytokeratin 18 (CK18), cholangiocyte-specific protein CK19, smooth muscle cell-specific protein α-SMA, the endothelial cell marker CD31, or the active fibroblast marker FAPα. Total macrophages of the liver were selectively stained in cryosections incubated with anti-CD68 antibodies (1:100, Abcam), while the M2a and M2c macrophage populations were selectively stained with anti-CD206 antibodies. Expression of interleukin and growth factor genes was evaluated with PCR-RT.RESULTSIntrasplenic allogeneic transplantation of the umbilical cord-derived multipotent stromal cells stimulates reparative processes within the residual liver tissue after subtotal resection (removal of 80% of the organ mass), as indicated by increased rates of hepatocyte proliferation and accelerated organ mass recovery. These effects may result from paracrine influence of the transplanted cells on the resident macrophage population of the liver. The transplantation favors polarization of macrophages to M2 phenotype (the M2-polarized macrophages specifically express CD206; they are known to suppress inflammation and support tissue repair). No differentiation of the transplanted cells into any of the liver cell types have been observed in the study.CONCLUSIONWe found no direct evidence for the paracrine effect of MSCs on liver regeneration after the subtotal liver resection in rats. However, the paracrine mechanism of the therapeutic activity of transplanted MSC is indirectly indicated by a decrease in the total number of CD68 + macrophages and an increase in the proportion of M2 pro-repair macrophages in the regenerating liver as compared to animals in which the transplantation was only mimicked.

Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats

Rapid regeneration of the remnant liver is critical for preventing liver failure and promoting recovery after extensive liver resection. Numerous studies have demonstrated the involvement of bone marrow-derived stem cells in liver regeneration and the potential benefits of bone marrow stem cell therapy. To avoid the preparation of stem cells, we proposed in this study to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (A), an antagonist of CXCR4 and low-dose FK506 (F). Here we show that AF combination therapy significantly increased lineage negative (Lin-) CD34+ and Lin-CD133+ stem cells in peripheral blood and enhanced recruitment of CD133+ cells into the remnant liver in a rat model of 85% partial hepatectomy. Recruiting CD133+ stem cells in the remnant liver was associated with increased proliferation of hepatic oval cells and paralleled the increased SDF-1, CXCR4 and HGF expression. Importantly, AF combination therapy increased the number of Ki67 positive hepatocytes and BrdU incorporation in the remnant liver and improved serum levels of albumin. Our results demonstrate that pharmacological mobilization of endogenous bone marrow stem cells with AF combination therapy can enhance endogenous stem cell mobilization to promote liver regeneration and improve liver function after extensive hepatectomy.

The influence of splenic artery ligation on the expression of transforming growth factor alpha during liver regeneration in partial liver resection rats

Objective To observe the expression of transforming growth factor alpha (TGF-α) during liver regeneration after partial hepatectomy and splenic artery ligation, and study the influence of the splenic artery ligation on liver regeneration. Methods Seventy-two male rats were randomly divided into three groups: the sham operation group (A group) given the sham operation; 70% hepatectomy group (B group) given 70% liver resection; 70% hepatectomy and splenic artery ligation group (C group) griven splenic artery ligation and 70% liver resection. Each group was divided into subgroups of 24, 48, 72 h after the operation. The expression levels of TGF-α in liver tissues were measured by immunohistochemical methods. Serum TGF-α levels were determined by enzyme-linked immunosorbent assay (ELISA). Results As compared with A group, the levels of serum TGF-α at 24, 48 and 72 h after the operation was significantly incressed in the B group [(242.35±9.33), (163.64±9.22), (206.42±8.42) pg/ml] and C group [(259.00±11.50), (170.77±9.04), (212.12±10.63) pg/ml, P=0.000]. The expression levels of TGF-α in liver tissues were notably increased at 24, 48 and 72 h after the operation in the B group and C group (P=0.000). As compared with B group, the level of serum TGF-α and the expression of TGF-α in liver tissues were both increased at 24 h after the operation in C group (P=0.006, P=0.019). There were no significant differences between B group and C group in the level of serum TGF-α and the expression of TGF-α in liver tissues at 48 and 72 h (P=0.163, P=0.074, P=0.194, P=0.096). Conclusion The expression of TGF-α at 24 h after the 70% hepatectomy was promoted by the splenic artery ligation. The finding demonstrated that the splenic artery ligation can promote liver regeneration at early stage (about 24 h) after 70% liver resection in rats. Key words: Transforming growth factor alpha; Splenic artery ligation; Liver regeneration; Rat; Hepatectomy

Activity of NOTCH-signaling pathway after subtotal liver resection in rats

Activity of NOTCH-signaling pathway after subtotal liver resection in rats

The effects of quercetin on liver regeneration after liver resection in rats.

The aim of the present study was to assess the influence of quercetine (QE) on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Wistar albino rats were divided into three groups: sham-operated (SH), PH and PH+QE; each group contain 8 animals. The rats in QE-treated groups were given QE (15 mg/kg body weight) once a day i.p., for 7 days starting 3 days prior to hepatectomy operation. At 7 days after resection, liver samples were collected. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labelling, proliferation index (PI), transferase-mediated dUTP nick end-labelling assay, apoptotic index (AI) were evaluated at 7 days after hepatectomy. As a result, QE significantly increased MI, PI, and significantly decreased AI in PH rats. Additionally, QE remarkably inhibited the elevation of MDA, restored impaired antioxidant SOD activity and GSH level, and also attenuated hepatic vacuolar degeneration and sinusoidal congestion. These results suggested that QE treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative, antiapoptotic and proliferative property.

The effects of quercetin on liver regeneration after liver resection in rats.

The aim of the present study was to assess the influence of quercetine (QE) on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Wistar albino rats were divided into three groups: sham-operated (SH), PH and PH+QE; each group contain 8 animals. The rats in QE-treated groups were given QE (15 mg/kg body weight) once a day i.p., for 7 days starting 3 days prior to hepatectomy operation. At 7 days after resection, liver samples were collected. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labelling, proliferation index (PI), transferase-mediated dUTP nick end-labelling assay, apoptotic index (AI) were evaluated at 7 days after hepatectomy. As a result, QE significantly increased MI, PI, and significantly decreased AI in PH rats. Additionally, QE remarkably inhibited the elevation of MDA, restored impaired antioxidant SOD activity and GSH level, and also attenuated hepatic vacuolar degeneration and sinusoidal congestion. These results suggested that QE treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative, antiapoptotic and proliferative property.

Sa1612 70% Liver Resection in Rats. Pentadecapeptide BPC 157, L-Arginine, L-NAME: BPC 157 Beneficial Effect Counteracts Worsening Induced by L-NAME

Sa1612 70% Liver Resection in Rats. Pentadecapeptide BPC 157, L-Arginine, L-NAME: BPC 157 Beneficial Effect Counteracts Worsening Induced by L-NAME

Cytokines and growth factors genes expression after subtotal liver resection in rats

Cytokines and growth factors genes expression after subtotal liver resection in rats

Systemic Hemodynamic Changes after Maximally Allowable Liver Resection in Rats

Objective: to experimentally reveal possible systemic hemodynamic changes after maximally allowable liver resection, by determining the time of their formation in the early postoperative period. Materials and methods. The experiments on 22 outbred male albino rats recorded an electrocardiogram, left carotid blood pressure by a direct method, an integral rheogram and its first derivative by the tetrapolar rheographic procedure developed by Sh. I. Ismailov et al. and modified by V. V. Karpitsky et al. 1, 3, 6, and 12 hours and 1, 3, and 7 days after maximally allowable liver resection. Stroke volume, mean blood pressure, cardiac output, and specific peripheral vascular resistance (SPVR) were calculated. Blood loss was estimated by the gravimetric method. The significance of differences was defined by Friedman ANOVA. Results . At postoperative hour 1, the low cardiac output syndrome the basis for which is a considerable reduction in stroke volume developed and persisted during the first 24 hours; an additional contribution was made by moderate bradycardia observed within the first 24 hours. On day 3 postsurgery, the hemodynamic parameters were similar to those at baseline. By 7 day of an observation, cardiac depression changed into moderate myocardial hyperdynamia in the presence of moderate tachycardia and a moderate decrease in SPVR. Conclusion . The critical time found by the authors for the minimum cardiac output was an hour after surgery. The distinctive features of low cardiac output syndrome after maximally allowable liver resection are its reversible pattern and reflectory bradycardia on postoperative day 1. By day 7, cardiac depression changed into moderate myocardial hyperdynamia due to a tendency towards tachycardia.

Regulation of Heme Oxygenase 1 Expression by miR-27b With Stem Cell Therapy for Liver Regeneration in Rats

Adipose-derived mesenchymal stem cells (ASCs) have been considered to be attractive and readily available adult mesenchymal stem cells (MSCs) and are becoming increasingly popular for use in regenerating cell therapy. However, recent evidence attributed a fibrotic potential to MSCs which differentiated into myofibroblasts with highly increased α-smooth muscle actin (α-SMA) expression while transplanted into an injured/regenerating liver in mice. In this study, we studied the role of miR-27b in ASCs and their regenerative potential after partial liver resection in rats. ASCs transfected with control siRNA or miR-27b were intravenously injected into autologous rats undergoing 70% partial hepatectomy (PH). Our data showed that the regenerative capacities of ASCs with overexpressed miR-27b were significantly higher compared with control ASCs. However, the enhanced regeneration, hepatic differentiation, and suppressed liver inflammation, as well as fibrotic activity, were significantly reverted by ZnPP coadministration (heme oxygenase-1 [HO-1] inhibitor) indicating an important role of HO-1 in the regenerating and cytoprotective activities of miR-27b–transfected ASCs. We demonstrated that administration of autologous ASCs overexpressed with miR-27b enhances rapid and early liver regeneration and, importantly, preserves function after PH. The ASCs with miR-27b overexpression might offer a viable therapeutic option to facilitate rapid recovery after liver resection.

Lipids in Parenteral Nutrition on Liver Regeneration After Massive Liver Resection in Rats

Aim: The aim of this study is to elucidate the influence of lipids contained in the parenteral nutrition (PN) solution on hepatic regeneration and steatosis after massive hepatectomy when the animals are fed with total PN. f METHODS: Four groups of young adult rats were used according to the different types of PN and the harvesting time. In each animal, 75% partial hepatectomy and central line insertion via the internal jugular vein for PN were performed. Either lipid-free (PNG) or lipid-containing (PNL) PNs were used, both of which were isocaloric and isonitrogenous formula. Animals were sacrificed after 24 hours or 48 hours of PN infusion. Cell proliferation marker Ki-67, mitotic index, and relative liver weight gain were utilized to assess hepatic regeneration. Hepatic steatosis was evaluated by the histologic findings of the regenerating liver. RESULTS: Ki-67 index was significantly higher in the lipid-containing PN groups compared to the lipid-free PN groups at 24 and 48 hours (p=0.023 and p=0.008, respectively). Mitotic index was significantly higher in the lipid-containing PN group compared to the lipid-free PN at 48 hours (p=0.036) and a similar pattern was noticed for the fatty changes (p=0.005). CONCLUSION: Lipid-containing PN seemed to enhance liver regeneration and increase hepatic steatosis in rats after 75% hepatectomy compared to lipid-free PN within a short-term period.

Pentadecapeptide BPC 157 after 70% liver resection in rats

We suggest that stable gastric pentadecapeptide BPC 157 improves function and liver regeneration after 70% liver resection in rats since it can rescue otherwise severe liver lesions after overdose of paracetamol, diclofenac, ibuprofen, insulin, CCl4 or chronic alcohol abuse (for review see, i.e., Curr Pharm Des. 2012). Stable BPC 157 was applied (10 μg, 10 ng) (/kg) either ip once daily or in drinking water (0.16 μg; 0.16 ng/ml/12ml/day) till the sacrifice (at day 3, 7, 14, 21, 28). BPC 157‐rats maintained the weight, exhibited better liver regeneration based on better liver mass/body weight ratio (i.e., 14 days: 0.037 +/−0.004 (BPC 157) vs. 0.023+/− 0.005 (control); 28 days: 0.053+/−0.007 (BPC 157) vs. 0.03 +/− 0.004 (control)) and larger liver volume in pentadecapeptide BPC 157‐rats. Unlike constantly increased AST, ALT, bilirubine levels in controls, BPC 157‐rats after a short post‐surgery increase, mostly presented values comparable to non‐resected animals (conforming functional liver regeneration). Microscopically, controls presented larger areas of liver steatosis and liver fibrosis unlike BPC 157‐rats. Although binuclear cells were sporadically seen in controls, there were less hepatocytes with mitosis compared to all BPC 157 regimens. Supported by Grant 108–1083570‐3635, Croatia