• 한국방사선학회논문지
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• 제13권4호
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• pp.539-546
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• 2019

간조직 생검은 침습적이며, 합병증의 위험을 동반함에도 불구하고 간섬유화의 정도를 예측하는 표준 진단법으로 적용된다. 이러한 단점을 보완하기 위해 본 연구에서는 만성 C형간염 환자 200명을 대상으로 Fibroscan(R)을 이용하여 간섬유화 등급을 나누고, ROC 곡선을 측정하여 혈청학적검사로 계산되는 FIB-4, APRI, AAR의 유용성과 실질적인 Cut-off value를 알아보고자 하였다. 그 결과 간섬유화 평가를 위해 AAR을 적용하는 것보다는 APRI, FIB-4를 이용하는 것이 적절할 것으로 생각되며, 경한 섬유화 등급을 예측하기 위해서는 APRI, 간경변군인 F4등급에는 FIB-4를 사용하는 것이 유용하다고 판단된다. 혈청학적 간섬유화 표지자의 간편하고 반복 측정이 가능하다는 장점을 이용해 간 섬유화의 경과 관찰 기간을 줄일 수 있으므로 나아가 간경변과 간암의 유병률을 감소시킬 수 있을 것으로 사료된다.

• 대한방사선기술학회지:방사선기술과학
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• 제42권5호
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• pp.345-350
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• 2019

Liver biopsy is the gold standard for diagnosing liver fibrosis, but it is invasive and has a risk for complications. For this reason, recently, study has been actively conducted on non-invasive liver fibrosis evaluation method. But, there is no established standard for the type of diffuse liver disease. Therefore, this study was suggest the usefulness and cut-off values of Fibroscan, FIB-4, APRI and AAR of patients with hepatitis C in Korea. According to the diagnosis, 240 people in hepatitis C are classified into fatty liver, chronic hepatitis, and liver cirrhosis. The statistical analysis was performed by ANOVA to verify difference between groups. The ROC curve was analyzed to determine the usefulness and practical cut-off value. As a result, for all diseases, the AUC value for Fibroscan was 0.8 over and the APRI was 0.7 over. Cut-off value of serum based liver fibrosis markers was increased in order of fatty liver, chronic hepatitis and liver cirrhosis. If Fibroscan and serological liver fibrosis markers are applied to predict liver fibrosis, it is expected that excessive liver biopsy can be reduced.

• Journal of Korean Biological Nursing Science
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• 제8권2호
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• pp.41-59
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• 2006

Chronic liver diseases and hepatic cancer have been reported as 10% of cause of death in Koreans. Regardless of various causes, chronic liver disease accompanies commonly hepatic fibrosis. But still the mechanism of hepatic fibrosis remains poorly understood. Using the dimethylnitrosamine(DMN)-induced hepatic fibrosis rat model, We performed to evaluate the possible therapeutic effect of RIP(extracts of Phellodendron amurense and Patrinia scabiosaefolia) and to investigate the changes in referential connective tissue proteins($TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin, and vimentin) as a marker of fibrogenesis. For these purposes, liver tissues were stained with H & E, and Azan staining for estimation of developing fibrosis. In the DMN-treated rat liver tissue, fibrosis were developed forming incomplete septal fibrosis. Whereas, in the RIP-treated rat liver tissues, the fibrosis were decreased recovering to normal morphology. The expressions of $TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin($\alpha-SMA$), and vimetin were increased in the DMN-treated rat liver tissues, but decreased in the various areas of RIP-treated rat liver tissues. According to these results, RIP could be a possible therapeutic agent to reduce hepatic fibrosis, and the $TGF-{\beta}_1$, ${\alpha}$-SMA, and vimentin could be possible indicative markers of hepatic fibrosis development and recovery.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.112-118
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• 2001

The effects of Malloti Cortex Water Extract (MCWE), bergenin (isolated as an active component from MCWE), and acetylbergenin (synthesized from acetylation of bergenin) on the liver fibrosis induced by bile duct ligation (BDL) in rats. We studied hydroxypro1ine (HYP) as a marker of collagen accumulation in the liver, alanine aminotransferase (s-ALT), aspartate aminotransferase (s-AST), and alkaline phosphatase (s-ALP) as serum markers of liver cell damage induced by BDL, MCWE, bergenin, and acetylbergenin decreased towards normal the accumulated levels of HYP in the liver and the elevated serum levels of s-ALT, s-AST and 5-ALP. The results indicate that MCWE, bergenin, and acetylbergenin ameliorated the liver damage induced by BDL in rats.

• Toxicological Research
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• 제17권3호
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• pp.187-194
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• 2001

The oxidative stress causes the cell damage and death and thereby, stimulates membrane lipid peroxidation. In this study, the correlation between the lipid peroxidation product and the parameter of liver fibrosis (cirrhosis) was investigated in cholestasis induced rats. The Sprague-Dawley rats were divided into 3 groups (sham: sham operation, BDL/S-I and BDL/S-II : bile duct ligation/scission) and were observed for 2 or 4 weeks. After observation period, the organs were weighed and the ratio of organ weight/body weight was calculated. Sera and liver tissue were used for the measurement of malondealdehyde (MDA), parameter of clinical biochemistry, total collagen content and the staining. The ratio of organ weight/body weight in BDL/S-I and BDL/S-II was significantly increased compared to sham operated group. Serological parameters (Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and Total bilirubin) in BDL/S-I and BDL/S-II group were significantly higher than those in sham operated group. Concentration of MDA in BDL/S-I (261%) and BDL/S-II(790%) was significantly increased compared to MDA in sham operated group. And the content of hydroxyproline (hyp) in BDL/S-I and BDL/S-II group was significantly increased 2~4 times than in sham operated group. The good correlations between hyp in liver tissue and MDA in sera of sham operated group and all operated group were found (r=0.825). The significantly higher value of MDA, hyp and serological parameters in BDL/S-I and BDL/S-II group suggests the stimulation of lipid peroxidation and chronic liver damage. Especially the activation of lipid peroxidation and the stimulation of liver fibrosis was stronger in BDL/S-II group than in BDL/S-I group. The stronger fibrosis, portal-portal septum formation, the more massive bile duct proliferation in portal triads and stroma, and hepatocytes swelling were observed in liver tissue of and BDL/S-II group compared to BDL/S-I group. Conclusively, a good correlation between MDA as a lipid peroxidation marker and hyp as a liver fibrotic parameter could be connected with the process of liver fibrosis. Moreover, cholestasis condition may cause jaundice, activation of lipid peroxidation, and collagen accumulation in liver. Additionally, optimal observation period of bile duct obstruction for the screening of antioxidant and antifibrotic effect in rats would be four weeks.

• 약학회지
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• 제40권5호
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• pp.550-557
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• 1996

One of therapeutics in liver disease (morbus wilson) is D-penicillamin (D-pen: D-3-mercapto-valin). Especially the cross-linking of collagen molecules could be inhibited by D-pe n in extracellular space. In this study we investigated the antifibrotic effects of D-pen in rats that were induced the liver fibrosis by bile duct ligation and scission (BDL/S). Rats were treated for 4 weeks with D-pen after BDL/S operation or sham operation. The balance between fibrogenesis-marker (PNIIIP) and the fibrolysis-maker (PNIVP) were observed in sera by RIA (radioimmunoassay), and the parameter of collagen deposition in liver tissue (hydroxyproline: HYP) was measured by colorimetry. The weight of liver in BDL/S operated group was increased significantly in compared with sham operation group (15.2g${\pm}$1.1, vs 11.9g${\pm}$3.9: p<0.005, p<0.05). The rats group treated by D-pen showed the lower level of PNIIIP (6.7ng/ml${\pm}$1.5, vs 9.5ng/ml${\pm}$2.8) and the higher value of PIVCP (14.0ng/ml${\pm}$1.9, vs 7.9ng/ml${\pm}$1.5) in sera that compared to untreated rats. The content of HYP was decreased by 141% in BDL/S with D-pen treated group than that of it in BDL/S group. No correlation was revealed between collagen parameters in sera and HYP in liver tissue of BDL/S operated and D-pen treated rats. The group treated with D-pen showed the lower value of clinical biochemistry parameters (GOT: glutamate oxalacetate transaminase, Total-Bilirubin) in compared with only BDL/S operated rats, but the value of GPT (glutamate pyruvate transaminase) and Alkaline phosphatase in two BDL/S groups was nearly same. In the histological finding, we observed mild bile duct proliferation, weak inflammation and fibrosis in BDL/S with D-pen treated group, but BDL/S operated group showed the formation of septum (island of hepatocytes), massive bile duct proliferation. This result represents that the BDL/S operation induces liver fibrosis (cirrhosis) in 4 weeks, and D-pen inhibits the synthesis of collagen weakly and stimulates the degradation of collagen in the extracellular space. We conclude that the monitoring of PNIIIP, PIVCP in sera is useful parameter for screening of antifibrotic effect, and D-pen delay the liver fibrosis.

• 대한임상검사과학회지
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• 제43권3호
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• pp.113-119
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• 2011

This study was designed to determine the effects of larval extracts from Protaetia brevitarsis seulensis shade dried larva from Korea and China on liver tissues of hepatic injury groups. The experimental groups are divided into five groups; Normal, carbon tetrachloride single injection ($CCl_4$), Pb-CHI ($CCl_4$ + P. brevitarsis shade dried larva from China), Pb-KOR ($CCl_4$ + P. brevitarsis shade dried larva from Korea) and SIL ($CCl_4$ + 0.35% silymarin) groups. Sprague Dawley rats were oral injected with $CCl_4$ at a dose l mg/kg (20% in corn oil) for induction of liver damage for 4 weeks. Each experimental group was fed with a dose 50 mg/kg of larval extracts based on medicinal preparations from 3 weeks to 4 weeks after $CCl_4$ treatment. At the end of 4 weeks, we evaluated the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transferase (GPT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) in serum and the cytokine levels of tumor necrosis factor-${\alpha}$) (TNF-${\alpha}$) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the cells isolated from spleen and liver. The histological analysis was also conducted. The $CCl_4$ injection reduced body weight, induced congestion of middle lobe and hepatocytic degeneration, resulting in disintegration of hepatic cords, and increased biochemical markers of blood related to hepatic injury. On the other hand, the Pb-CHI and Pb-KOR group decreased the levels of biochemical markers in blood and cytokine levels in spleen and liver. Especially, the Pb-KOR group facilitated the recovery of biochemical values of blood related to hepatic injury, hepatic lesions and fibrosis. Taken together, larval extract from P. brevitarsis might prevent acute hepatotoxicity and enhance the recovery of liver fibrosis and cirrhosis induced by $CCl_4$, and the ingredients could be a promising candidate for the prevention and treatment of hepatic disorders.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.605-610
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• 2014

Chronic liver diseases, including cancer, are characterized by inflammation and elevated serum ferritin (SF). However, the causal-relationship remains unclear. This study used primary rat hepatic stellate cells (HSC) as a model to investigate effects of physiological SF concentrations (10, 100 and 1000 pM) because HSCs play a central role in the development and progression of liver fibrosis. Physiological concentrations of SF, either horse SF or human serum, induced pro-inflammatory cytokine $IL1{\beta}$, IL6 and $TNF{\alpha}$ secretion in rat activated HSCs (all p<0.05). By contrast, treatment did not alter activation marker ${\alpha}SMA$ expression. The presence of SF markedly enhanced expression of Grp78 mRNA (p<0.01). Furthermore, transient knock down of Grp78 by endotoxin EGF-SubA abolished SF-induced $IL1{\beta}$ and $TNF{\alpha}$ secretion in activated HSCs (all p<0.05). In conclusion, our results showed that at physiological concentrations SF functions as a pro-inflammatory mediator in primary rat HSCs. We also provide a molecular basis for the action of SF and identified Grp78-associated ER stress pathways as a novel potential therapeutic target for resolution of fibrosis and possible prevention of liver cancer.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제2권2호
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• pp.185-193
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• 1999

목 적: 답즙 정체를 주 소견으로 하는 만성 간질환의 대부분에서 담소관의 증식과 간섬유화가 관찰된다. 특히 간외 담도 폐쇄증에서 가장 현저하다. 그러나 섬유화의 병인에 대해서는 아직까지 많은 논란이 제기되고 있다. 총담관 결찰 후 시간이 경과함에 따른 담소관의 증식과 간섬유화의 진행과정 및 간섬유화에 대한 Ito 세포의 역할을 형태학적으로 조사하고자 본 연구를 하였다. 방 법: 건강한 Sprague-Dawley계 수컷 흰쥐를 대상으로 총담관을 결찰한 후 15일, 21일, 24일, 28일째에 도살하여 담소관의 증식과 간 섬유화의 진행과정을 smooth muscle actin에 대한 면역조직화학적 염색과 전자현미경적 검사를 하였다. 결 과: 1) 총담관 결찰후 시간이 경과할수록 간문맥 중심으로 담소관의 증식과 결체조직의 증식이 증가하였다. 2) 면역조직화학적 검색에서 활성화된 Ito 세포는 smooth muscle actin에 양성반응을 보였고, 총담관 결찰후 시간이 경과할수록 담소관주위와 동모양혈관 주의에서 많이 관찰되었다. 3) 전자현미경적 관찰에서 총담관결찰 후 시간이 경과함에 따라 Ito 세포가 증가하였으며, 지방적의 수가 감소한 근섬유모 세포를 닮은 Ito 세포와 근섬유모 세포의 수가 증가하였다. 결 론: 총담관 결찰후에 볼 수있는 간 섬유화는 활성화된 Ito 세포의 증가와 Ito 세포가 교원질을 분비하는 근섬유 모세포로 변형되기 때문에 생긴 것으로 생각된다.

• 한방비만학회지
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• 제18권1호
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• pp.19-26
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• 2018

Objectives: Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis. The objective of this study is to investigate the effects of Scutellaria Radix (SR) extract on the alcoholic fatty liver induced by long-term EtOH administration. Results: Male Sprague Dawley rats were used in this study. All animals were randomly divided into Normal group, treated with saline (n=10); EtOH group, treated with ethanol (n=10); EtOH+SR group, treated with ethanol+Scutellaria Radix extract (n=10). For oral administration of ethanol in EtOH and EtOH+SR group, the ethanol was dissolved in distilled water in concentrations of 25% (v/v). Throughout the experiment of 8 week, the rats were allowed free access to water and standard chow. Sample group were administrated by Scutellaria Radix extract daily for 8 weeks. Results: The levels of hepatic marker such as aspartate aminotransferase and alanine aminotransferase were altered. Histopathological changes such as ballooning, fatty and hydropic degeneration were reduced and the expression of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) was significantly attenuated by Scutellaria Radix extract. Conclusions: These data suggest that Scutellaria Radix extract attenuated the alcoholic simple fatty liver by improving hepatic lipid metabolism via suppression of $TNF-{\alpha}$ protein. Scutellaria Radix could be effective in protecting the liver from alcoholic fatty liver.