• 대한한방내과학회지
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• 제19권1호
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• pp.3-21
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• 1998

This study was to investigate the effects of Gibangganbang on the liver injury induced dimethylnitrosamine, CCl4, ethanol and partial hepatectomy. Hydroxyproline, hepatic fibrosis, hepatic inflammatory cell infiltration, fatty value, lipidoperoxide levels, glutathione levels, mitotic index, contents of protein in the serum and liver tissues were measured and observed. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by dimethylnitrosamine in mice was decreased by the oral administration of Gibangganbang. 2. The degree of hitological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ was decreased by the oral administration of Gibangganbang. 3. The degree of fatty value and the increasing level of lipidoperoxide in liver tissues was decreased by the oral administration of Gibangganbang. 4. The level of glutathione in liver tissues was increasing by the oral administration of Gibangganbang. 5. The increasing level of microsomal lipidoperoxide in vitro assay was decreasing by the oral administration of Gibangganbang. 6. The increasing level of the mitotic index, weight of liver, contents of protein, RNA and DNA synthesis of the liver tissues after partial hepatectomy was activated by the oral administration of Gibangganbang. These results suggest that Gibangganbang not only inhibits liver cirrhotic change and ethanol-induced fatty change but also activates antioxidant enzymes and regeneration ability ocf liver.

• 대한수의학회지
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• 제39권1호
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• pp.169-176
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• 1999

The purposes of this study were to set up the method of the natural killer(NK) cell activity assay using the flow cytometer and to examine the characteristics and distribution of the NK cell during rat hepatocarcinogenesis. Forty five male 6 week-old specific pathogen free(SPF) Sprague-Dawley rats were randomly divided into three groups. Group I was the non-treated control and given normal diet and water. Group II was treated with diethylnitrosamine(DEN, 200mg/kg, i.p.) and partial hepatectomy. Group III was treated with DEN, partial hepatectomy and 0.05% phenobarbital sodium in water from 3 to 16 weeks. All animals were examined the morphology of the large granular lymphocyte(LGL), the LGL percent of the total lymphocytes and the LGL conjugation rate with YAC-1 cell in peripheral blood, spleen and liver. Moreover, activity of the LGL isolated from peripheral blood lymphocytes was determined using the flow cytometer. As results, LGL were observed in the peripheral blood, spleen and liver. LGL were observed the relatively faintly staining basophilic cytoplasm with granules, and eccentric, often kidney-shaped nuclei in Giemsa stain. Its size was $11{\sim}13{\mu}m$. LGL percentage of the isolated lymphocytes in peripheral blood, spleen and liver were 1.8~2.3%, 1.3~1.4% and 0.87~0.99%, respectively. LGL conjugation rate with YAC-1 cell was shown to be peripheral blood(9.3~10.3 %) > spleen(7.7~8.7%) > liver(5.6~7.0%). The activity of the LGL isolated from peripheral blood lymphocytes in Group I, II and III was 33.7%, 30.5% and 35.4%, respectively. However, all values were not significantly between groups.

• 약학회지
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• 제36권2호
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• pp.180-187
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• 1992

This study investigated the hypothesis that carcinogen-induced elevation of oxyradical during the hepatocarcinogenesis in rat. The hepatic preneoplastic lesions in the Spraque-Dawley rats were induced by the carcinogen treatment such as diethylnitrosamine(DEN) and acetylaminofluorene(AAF) in combination with partial hepatectomy(PH). The liver sample was taken at 2, 6, 10 and 16 months after carcinogen treatments followed by PH. Carcinogen treatments initially increased the indices of oxidative damage(activities of xanthine oxidase and production rates of superoxide anion, microsomal hydrogen peroxide, hydroxyl radical) in the liver compared to PH groups. However, cytosolic hydrogen peroxide did not change significantly throughout the full time period. Of hydrogen peroxide scavenger, the catalase was remained lower than PH groups, whereas the peroxidase was increased after carcinogen treatments. Morphologically, the immunohistochemical analysis with glutathione-S-transferase of a placenta form(GSTP) antibody was used to detect the induction of preneoplastic nodules. During the hepatocarcinogenesis, both production rate of hydroxyl radical and activity of glutathione-S-transferase(GST) markedly increased with the appearance of the preneoplastic nodule. These results indicated that the hydroxyl radical of reactive oxygen species seemed to have a major influence on the hepatocarcinogenesis and the effect of time after removal of the carcinogen also appeared to be highly critical in the hepatocarcinogenesis.

• BMB Reports
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• 제55권8호
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• pp.401-406
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• 2022

Ahnak, a large protein first identified as an inhibitor of TGF-β signaling in human neuroblastoma, was recently shown to promote TGF-β in some cancers. The TGF-β signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-β signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -β/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostaining, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-β signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-β expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-β signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment.

• BMB Reports
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• 제55권12호
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• pp.633-638
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• 2022

Liver regeneration is a well-known systemic homeostatic phenomenon. The N⁶-methyladenosine (m⁶A) modification pathway has been associated with liver regeneration and hepatocellular carcinoma. m⁶A methyltransferases, such as methyltransferase 3 (METTL3) and methyltransferase 14 (METTL14), are involved in the hepatocyte-specific-regenerative pathway. To illustrate the role of METTL14, secreted from non-parenchymal liver cells, in the initiation phase of liver regeneration, we performed 70% partial hepatectomy (PH) in Mettl14 heterozygous (HET) and wild-type (WT) mice. Next, we analyzed the ratio of liver weight to body weight and the expression of mitogenic stimulators derived from non-parenchymal liver cells. Furthermore, we evaluated the expression of cell cycle-related genes and the hepatocyte proliferation rate via MKI67-immunostaining. During regeneration after PH, the weight ratio was lower in Mettl14 HET mice compared to WT mice. The expressions of hepatocyte growth factor (HGF) and tumor necrosis factor (TNF)-α, mitogens derived from non-parenchymal liver cells that stimulate the cell cycle, as well as the expressions of cyclin B1 and D1, which regulate the cell cycle, and the number of MKI67-positive cells, which indicate proliferative hepatocyte in the late G1-M phase, were significantly reduced in Mettl14 HET mice 72 h after PH. Our findings demonstrate that global Mettl14 mutation may interrupt the homeostasis of liver regeneration after an acute injury like PH by restraining certain mitogens, such as HGF and TNF-α, derived from sinusoidal endothelial cells, stellate cells, and Kupffer cells. These results provide new insights into the role of METTL14 in the clinical treatment strategies of liver disease.

• Journal of Trauma and Injury
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• 제19권1호
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• pp.59-66
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• 2006

Purpose: Acute liver failure after massive partial hepatectomy is critical condition with high mortality. To prevent postoperative liver failure from being induced by a massive partial hepatectomy, many doctors do a minimal resection on the single lobe of the liver that might cause postoperative bleeding from the remaining ruptured parenchyma. The objective of this study was to assess clinical experience with postoperative hepatic arterial embolization to control bleeding from the remaining ruptured liver during the postoperative period. Methods: This retrospective 4-year study was conducted from May 2002 to April 2006 and included consecutive patients who had sustained massive hepatic injuries and who had undergone a laparotomy, followed by postoperative hepatic arterial angiographic embolization to control bleeding. Data on the injury characteristics, the operative treatment and embolization, and the amount of transfused packed red cells (PRBC) were gathered and analyzed. In addition, data on the overall complications and survival rate were collected and analyzed. Results: Every case showed severe liver injury, higher liver injury scaling grade IV. Only ten cases involved a ruptured bilateral liver lobe. A lobectomy was done in 6 cases, a left lobectomy was done in 3 cases, and a primary suture closure of the liver was done in 2 cases. Suture closure was also done on the remaining ruptured liver parenchyma in cases of lobectomies. The postoperative hepatic arterial embolizations were done by using the super-selection technique. There were some cases of arterio-venous malformations and anomalous vessel branches. The average amount of transfused PRBC during 24 hours after embolization was $2.36{\pm}1.75$, which statistically significantly lower than that before embolization. Among the 11 cases, 9 patients survived, and 2 died. There was no specific complications induced by the embolization. Conclusion: In cases of postoperative bleeding in severe hepatic injury, if there is still a large amount of bleeding, postoperative hepatic arterial embolization might be a good therapeutic option.

• Applied Microscopy
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• 제35권1호
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• pp.15-22
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• 2005

진핵세포 내에 존재하는 metallothionein (MT)은 시스테인 함량이 높은 저분자량의 단백질로서 2가 금속이온들과의 친화력이 높아 중금속에 대한 해독작용, 금속이온의 대사 및 세포분열 등과 관련되어 있다. 본 연구자들은 간 재생능력이 우수한 흰쥐를 실험모델로 하여, 간의 70% 정도를 실험적으로 제거한 후, 간 재생을 유도하는 과정에서 시간 경과에 따라 간세포의 미세구조 변화와 더불어 MT 유전자 발현 및 이 단백질의 세포내 분포를 알아보고자 하였다. 부분 간 절제 후 간 조직이 증식되고 재구성되어 간이 원래의 크기로 재생되는 시간은 1주일 정도가 소요되었다. 재생중인 간세포는 핵대 세포질의 비가 크고, 핵내에 인이 크게 발달하고 크기가 작은 미토콘드리아가 다수 나타났으며, 조면소포체가 잘 발달하고 있었다. MT mRNA는 간 절제 직후부터 증가하기 시작하여 1시간 경과 후에 최대치에 이르렀고, 12시간 이후부터 감소하기 시작하였다. 재생중인 간세포에서 MT에 대한 면역반응은 간 절제 후 12시간이 경과한 군에서 가장 높게 나타났고, 이후 점차 감소하여 8일이 경과한 실험군에서는 정상 대조군과 유사한 정도로 감소하는 것으로 관찰되었다. 또한, 간 재생 초기에는 항-MT 금 입자들이 주로 세포질쪽에 분포하다가 점차 핵내에 존재하는 양이 증가하는 것으로 나타났다. 이러한 결과들은 간 절제 후 보상작용으로 일어나는 세포분열 단계에서 MT가 이 과정에 필요한 요소를 제공하는 역할을 수행하기 때문인 것으로 사료된다.

• 한국동물학회지
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• 제27권4호
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• pp.221-230
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• 1984

Wistar계 흰쥐 간의 약 70%를 절제한 후 재생중인 나머지 간의 microsome에서 lipid peroxidation과 약물 대사효소중 특징적인 aminopyrine demethylase의 활성도를 측정하고 NADPH-cytochrome c reductase, glutathione peroxidase의 활성도와 cytochrome P-450의 함량을 측정하였다. Aminopyrine demethylase의 활성도는 재생 제1일에 최저치를 나타냈으며 재생이 진행될수록 정상인 수준으로 증가하였고 lipid peroxidation, NADPH-cytochrome c reductase, cytochrome P-450의 함량 역시 재생초기에 급히 감소하여 재생2일에 가장 낮은 값을 나타내며 점차 정상인 수준으로 증가하여 7일 이후에는 정상치에 도달하였다. Glutathione peroxidase의 활성도는 재생중인 간이나 정상인 개체의 간에서 별다른 차이가 없었다. 이것은 재생중인 간에서 재생초기에 cytochrome P-450의 함량과 NADPH-cytochrome c reductase의 활성도 감소가 lipid peroxidation과 약물 대사효소의 활성도 감소를 일으키며 이러한 현상은 부분 간 절제 후 7일 이후에는 거의 나타나지 않았다.

• Journal of Chest Surgery
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• 제9권2호
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• pp.117-124
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• 1976

Hemorrhage into the biliary system as a consequence of injury to the liver has been called "traumatic hemobilia," a term introduced by Sandblom in 1948. The source of gastrointestinal hemorrhage has been frequently misinterpreted, resulting in inadequate or inappropriate treatment, often with catastrophic results and needless fatalities. It is now being diagnosed with increasing frequency, due to more widespread knowledge of the syndrome and improved diagnostic means. we experienced 2 cases of hemobilia following blunt chest trauma, One patient had! multiple rib fractures on right chest by car traffic accident and 13 days later, suddenly massive melena was developed with nausea, vomiting, jaundice and severe pain on right upper quadrant. And so, he had operated on the ligation of Rt. hepatic artery and partial right hepatectomy for a traumatic hemobilia. The other one also revealed similar symptoms 20 days later following blunt chest injury by falling down accident. However, uneventful recovery was seen without any of surgical intervention in this case.

• Toxicological Research
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• 제7권1호
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• pp.93-112
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• 1991

This study was carried out to investigate the various factors on induction of experimental hepatocarcinogenesis in Sprauge-Dawley rats. The experimental animals were divided into three Experiment. Experiment I, II and III were began rats with initial age of 6, 16 and 55 weeks, respectively. All Experiment were injected intrapertioneal with diethylnitrosamine (DENA` 200 mg/kg) as an intiator and group 3, 4 of Experiment I, II and III were fed on diet containing 0.02% 2-acetylaminofluorene (2-AFF) as a promoter for 6 weeks. Three weeks after two-thirds partial hepatectomy was performed in group 2, 4 of Experiment I & II and group 3 of Experiment III.