인진사령산(茵蔯四苓散)이 흰쥐의 알콜성 지방간에 미치는 영향

김범회,Kim, Bum Hoi 대한한의학방제학회 2018 大韓韓醫學方劑學會誌 Vol.26 No.2

Objectives : Alcoholic fatty liver is an early and reversible consequence of excessive alcohol consumption. The initial hepatocyte cell death stimulates subsequent inflammatory responses, leading to further liver injury and fibrosis. The objective of this study is to investigate the effects of Injinsaryung-san extract on the alcoholic fatty liver by chronic EtOH administration. Method : 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+IS group, treated with ethanol+Injinsaryung-san extract (n=10). For oral administration of ethanol in Control and Sample 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 Injinsaryung-san extract daily for 8 weeks. Results : The levels of hepatic marker such as aspartate aminotransferase and alanine aminotransferase were altered. Histopathological changes were reduced and the expression of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) was markedly attenuated by Injinsaryung-san extract. Conclusion : These data suggest that Injinsaryung-san extract could be effective in protecting the liver from alcoholic fatty liver. The hepatoprotective mechanisms of Injinsaryung-san may be related to attenuation of $TNF-{\alpha}$ protein, as well as to the inhibition of inflammatory response in the liver. Therefore, Injinsaryung-san can be a candidate to protect against alcoholic fatty liver.

Effects of Danggwieumja on the Healing of Full-Thickness Skin Injury in Rat

김범회 한의병리학회 2011 동의생리병리학회지 Vol.25 No.5

The purpose of this study was to investigate the wound healing effects of Danggwieumja (DG), which is commonly used for skin inflammation, skin wound, skin pruritus, and chronic hives etc. The 1.5 cm × 1.5 cm full-thickness skin wound was induced to two groups, DG (n=16) and Saline (n=16) group. The DG extract and Saline were orally administrated daily for 15 days after skin wound induction. Then, the body weight of rats and the congestion indices were daily measured for 15 days after skin wound induction. The wound contractions and epithelizations were also measured. The wound contractions were daily measured for 15 days after wound induction and wound epithelizations were measured for 8 days from day 7 after wound induction. For evaluating angiogenesis, the immunoreactivities of vWF and VEGF protein were measured immunohistochemistrically on day 15. In results, although the percentage increases in mean body weight of rats in the DG and Saline groups hve no significant differences, DG extract decreased the time of wound healing and congestion around wound, and improved wound contraction and epithelization. The contraction percentage of DG group was significantly increased on day 5 (P<0.05) and day 7 (P<0.01) than that of Saline group. DG group showed significant increase of wound epithelization on day 7 (P<0.05) as compared to Saline group. Moreover, DG extract reduced the inflammation of skin dermis and promoted the growth of vascular vessels of dermis by accelerating vascular endothelial growth factor (VEGF) protein. These results suggest that DG has the beneficial effects on skin incision wound and can be the suitable wound healing agent for various surgical wounds.

흰쥐의 전층피부손상에서 온청음(溫淸飮)이 신생혈관형성에 미치는 영향

김범회,이해웅,손낙원,박동일,Kim, Bum-Hoi,Lee, Hae-Woong,Sohn, Nak-Won,Park, Dong-Il1 대한예방한의학회 2010 대한예방한의학회지 Vol.14 No.1

The wound healing process can be categorized as follows : inflammation, fibroplasia, neovascularization, collagen deposition, epithelialization, and wound contraction. During the healing process, various growth factors are secreted to accelerate wound healing. Previous studies have demonstrated that endogenous growth factors, such as vascular endothelial growth factor(VEGF) are the important regulatory polypeptides for coordinating the healing process. They are released from macrophages, fibroblasts, and keratinocytes at the site of injury and participate in the regulation of reepithelization, granulation tissue formation, collagen synthesis and neovascularization. Onchung-Um has been used clinically to treat various skin diseases. In addition, Onchung-Um has been also used for congestive inflammations. In the present study, we evaluated the effects of Onchung-Um on wound healing process and wound size reduction in rats. Full-thickness skin wounds ($15mm\;{\times}\;15mm$) were created on the back of rats. Rats were then divided into 2 groups : The Onchung-Um treated group that was orally administered with a dose of 193.9mg/100g of Onchung-Um extract per day for 15 days and Control group without Onchung-Um administration. Moreover, the histological changes and VEGF immunoexpressions of two groups were estimated. In results, wound closures were significantly accelerated by oral administration of Onchung-Um extract. Furthermore, in Onchung-Um treated group, there were significant increases in fibroblast migration, epithelialization compared with the Control group. VEGF expressions were also increased in Onchung-Um treated group. This study has therefore demonstrated the Onchung-Um can significantly improve the quality of wound healing and scar formation and the oral administration of Onchung-Um extract may increase early tissue angiogenesis in the incisional wound of an experimental animal model.

안존이천탕 추출물이 흰쥐의 모체 및 태자에 미치는 영향

김범회,Kim, Bum Hoi 대한예방한의학회 2013 대한예방한의학회지 Vol.17 No.2

The objective of this study was to characterize the adverse effects of Ahnjon-Yichun-Tang during early pregnancy. Following successful mating, female Sprague-Dawley rats were given Ahnjon-Yichun-Tang(AYT) extract by oral administration daily with dose of 150mg (n=10), 300mg(n=10), 450mg(n=10) for 20 days of pregnancy. The rats in Control group(n=10) were orally administrated with Saline. All pregnant rats of Ahnjon-Yichun-Tang-treated and Control groups were sacrificed on day 20 of pregnancy. The pregnancy outcome was determined and the internal and reproductive organs of pregnant rat were observed. The fetuses were examined for the presence of various developmental toxic endpoints and stained with alcian blue and alizarin red S, and observed skeletal malformations. The results obtained in this study represent that there is no significant changes between Control and Ahnjon-Yichun-Tang-treated groups in body weight, organ weight, blood chemistry values, hematological values and pregnancy indexes of pregnant rat. The skeletal malformation of fetus was not observed as well. These results suggest that oral administration of Ahnjon-Yichun-Tang does not produce either maternal or developmental toxicity.

Gerbil 전뇌허혈에 대한 大黃의 신경보호효과

김범회,정혁산,원란,박지호,강철훈,손낙원 대한한의학회 2002 대한한의학회지 Vol.23 No.3

목적 : 본 실험에서는 gerbil을 이용한 전뇌허혈동물모델에서 뇌허혈손상 직후 지연성 뇌손상에 대한 대황의 방어효과와 Apoptosis 과정중의 Bax와 Bcl-2 단백질에 대한 조절작용을 관찰하고, TUNEL 염색법을 통하여 대황이 gerbil hippocampus CA1 영역의 pyramidal neuron의 세포사에 미치는 영향과 PC12 세포를 이용한 세포배양모델에서의 대황의 신경방어 효과를 관찰하였다.방법: Mongolian gerbil의 총경동맥을 5분간 폐색하여 가역성 전뇌허혈을 유발시킨 후 대황의 전탕액을 하루에 한번 경구 투여하였다. 대황의 신경 보호 효과는 수술 7일 후에 cresyl violet으로 염색하여, 살아있는 신경 세포의 수를 세어 측정하였다. 또, 수술 3일후에는 면역조직화학적 방법을 통하여 Bax, Bcl-2 단백질의 발현과 대황의 신경보호 효과와의 관련성을 알아보았다. 결과 : 가역적 전뇌허혈이 일어난 동물군의 경우 hippocampus의 CA1 영역에서 살아있는 신경세포의 수는 51.0 2.5개 /mm에 불과하였으나, 그에 비해 수술 후 7일간 대황을 투여한 동물군은 106.2 2.5개 /mm로 살아있는 신경세포수가 크게 증가하였다. Apoptosis를 촉진하는 단백질인 Bax의 발현은 3일간 대황을 투여한 동물군의 경우 hippocampus의 CA1 영역에서 현저하게 저해되었고, apoptosis를 억제하는 Bcl-2 단백질의 발현은 변화가 없었다. TUNEL assay를 통하여 살펴본 결과 대황 투여군의 apoptotic 신경세포사가 감소하였으며 이는 Bax protein의 발현과 유사한 양상을 나타내었다.

흰쥐 발목관절고정으로 유발된 장딴지근 위축에 경혈점 자극이 미치는 효과

김범회,이태식 대한통합의학회 2018 대한통합의학회지 Vol.6 No.4

Purpose: Disuse atrophy is a type of muscle atrophy that results in a decrease in muscle size. Disuse muscle atrophy occurs in response to various pathologies, such as joint immobilization, inactivity, or bed rest. Oxidative stress, in which antioxidant proteins and scavenger protection are overwhelmed by reactive oxygen species (ROS) production, is recognized as one of the central causes of disuse muscle atrophy. ST36, known as the accupoint of Zusanli, is an acupuncture point on the lower leg and one of the most frequently used acupressure points in acupuncture. The present study tested the hypothesis that acupressure at ST36 would attenuate immobilization-induced skeletal muscle atrophy. Methods: The left hind limb was immobilized using casting tape (ST36 group, n = 10), and the animals were then treated daily with a pressure needle at accupoint ST36. Ten untreated animals with hind limb immobilization and no treatment served as a control group. After 2 weeks of immobilization, the morphologies of the right and left gastrocnemius muscles in both the ST36 and control groups were assessed by hematoxylin and eosin staining. Results: The acupressure at the accupoint of Zusanli conferred significant protection against reductions in left gastrocnemius muscle weights and average cross-sectional muscle areas in the ST36 group as compared with those in the control group. Moreover, the acupressure at the ST36 point significantly reduced malondialdehyde (MDA) activity in the gastrocnemius muscles as compared with that in the control group. Conclusion: These results suggest that acupressure at the accupoint of Zusanli provides protection against immobilization-induced muscle atrophy by decreasing MDA activity in gastrocnemius muscles. ‘불사용 근위축(disuse muscle atrophy)’은 팔다리의 고정, 오랜 침대생활, 혹은 척수손상이나 말초신경 손상에 의해 발생하며 결과적으로 뚜렷한 근육량의 감소와 수축력의 감소를 야기한다. 불사용에 따른 골격근위축은 실제 임상에서 흔하게 제기되는 문제이며, 특히 노령인구의 증가에 따라 주목받고 있는 임상적 문제이다. 인체의 많은 Acupuncture point 중에서 ST36(Zusanli)은 무릎뼈 바깥쪽 아래에 위치하는데, 주치 범위가 광범위하여 임상적으로 가장 많이 활용되며, 이곳에 대한 자극치료는 근골격질환, 소화기계통을 비롯한 내과질환 및 뇌혈관 질환 등에도 유효한 효과가 있는 것으로 알려졌다. 본 연구는 흰쥐의 발목관절을 2주간 붕대 고정하여 근육 불사용의 환경을 만들어 근위축을 유발시키고, 2주간 매일 ST36에 경혈압박을 가하여 불사용 근위축에 미치는 효과를 검증하고자 실험동물의 체중 변화, gastrocnemius 근육의 중량 및 근섬유 단면적 변화, 그리고 산화적 손상에 관련된 지표를 측정하였다. 그 결과, ST36 자극은 장기간의 근육 미사용으로 인한 실험동물의 체중변화에는 별다른 영향을 미치지 않았으나, gastrocnemius 근육 무게의 감소를 회복시켜주는 효과가 있었으며 동시에 근섬유의 단면적 감소를 억제시키는 것으로 확인되었다. 무게와 단면적 크기의 변화가 나타난 gastrocnemius에서 산화적 손상과 관련된 지표인 MDA 활성을 억제하는 것으로 밝혀졌다. 이와 같은 결과로 ST36 자극은 불사용 근위축 손상에 유의한 보호효과가 있는 것으로 사료된다.

대영전(大營煎)이 불용성 근위축에서의 apoptosis 관련 단백질들의 발현변화에 미치는 영향

김범회 대한한의학방제학회 2017 大韓韓醫學方劑學會誌 Vol.25 No.4

Objectives : Skeletal muscle atrophy occurs in response to a variety of conditions. The unloading to muscle occurs clinically in limb immobilization, bed rest, spinal cord injury and peripheral nerve damage, resulting in significant loss of muscle mass and force production. Muscle disuse is accompanied by an increase in apoptotic signaling, which mediates some of the responses to unloading in the muscle. In this study we tested the hypothesis that Daeyeoung-jeon extract would improve muscle recovery after reloading following disuse. Method : Twenty young male Sprague-Dawley rats were used for the studies. The hindlimb immobilization was performed with casting tape to keep the left ankle joint in a fully extended position. No intervention was performed on the right leg and used as intact region. The Rats in Daeyeoung-jeon treated group (DYJ) were orally administrated Daeyeoung-jeon water extract, and rats of Control group were given with saline only. After 2 weeks of immobilization, all animals were sacrificed, and the whole gastrocnemius muscles were dissected from both legs. The morphology of right and left gastrocnemius muscles in both DYJ and Control groups were assessed by hematoxylin and eosin staining. Moreover, to investigate the immobilization-induced muscular apoptosis, the immunohistochemical analysis of Bax and Bcl-2 was carried out. Results : Daeyeoung-jeon represented the significant protective effects against the reductions of the left gastrocnemius muscles weight and average cross section area to compared with Control group. The treatment with Daeyeoung-jeon extract significantly reduced the immunoreactivity of BAX and increased the immunoreactivity of Bcl-2 in gastrocnemius muscle compared with Control group. Conclusion : Daeyeoung-jeon has protective effects against immobilization-induced muscle atrophy by regulating the activities of apoptosis-associated BAX/Bcl-2 proteins in gastrocnemius muscle.

흰쥐의 급성 위점막 손상에서 황연탕(黃蓮湯)이 apoptosis 관련단백질 및 성장인자 발현에 미치는 영향

김범회,Kim, Bum-Hoi 대한예방한의학회 2012 대한예방한의학회지 Vol.16 No.1

The apoptotic process of gastric mucosa triggered by induction of proapoptotic gene expression, such as Bax. Stress-inducing factors may affect Bcl-2/Bax ratio and thus the rate of apoptosis through modulation of the expression of both proteins depending upon the experimental model. TGF-${\beta}$ is believed to be essential in wound healing for regulation of cell growth and differentiation and is known to be involved in tissue repair and remodeling. The polypeptide growth factors, such as vascular endothelial growth factor(VEGF), regulate essential cell functions involved in tissue healing including cell proliferation, migration, and differentiation. The purpose of this study was to investigate whether the oral administration of $Hwangyeon-tang$ (HYT) would have protect effects on gastric ulcer in rat. Sprague-Dawley rats (n=40) were randomly divided into 4 groups ; Normal, Saline, Cimetidine and HYT group. The saline, cimetidine and HYT extract were orally administrated to each group and gastric ulcer was induced with HCl/EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In Results, the wound healing of gastric ulcer was promoted by HYT and the significant alterations of BAX/Bcl-2, TGF-${\beta}1$ and VEGF proteins in gastric mucosa were observed. These results suggest that Fritillaria ussuriensis extract promotes wound healing and has protective effects on gastric ulcer in rats.

대금음자(對金飮子)가 흰쥐의 만성 알콜성 근위축에 미치는 영향

김범회,Kim, Bum Hoi 대한한의학방제학회 2016 大韓韓醫學方劑學會誌 Vol.24 No.3

Chronic alcoholic myopathy is one of the most common skeletal muscle disorders. It is characterized by a reduction in the entire skeletal musculature, skeletal muscle weakness, and difficulties in gait. Patients with alcoholic hepatitis and cirrhosis have severe muscle loss that contributes to worsening outcome. Although the myopathy selectively affects Type II (fast twitch, glycolytic, anaerobic) skeletal muscle fibers, total skeletal musculature is reduced. The severity of the muscle atrophy is proportional to the duration and amount of alcohol consumed and leads to decreased muscle strength. The mechanisms for the myopathy are generally unknown but it is not due to overt nutritional deficiency, nor due to either neuropathy or severe liver disease. Skeletal muscle mass and protein content are maintained by a balance between protein synthesis and breakdown and in vivo animal models studies have shown that ethanol inhibits skeletal muscle protein synthesis. Daekumeumja is a traditional Korean medicine that is widely employed to treat various alcohol-induced diseases. Muscle diseases are often related to liver diseases and conditions. The main objective of this study was to assess that Daekumeumja extract could have protective effect against alcoholic myopathy in a Sprague-Dawley rat model. Rats were orally given 25% ethanol (5ml/kg, body weight) for 8 weeks. After 30 minutes, rats were administrated with Daekumeumja extract. Controls were similarly administrated with the vehicle alone. The weights of gastrocnemius, soleus and plantaris muscles were assessed and the morphologic changes of gastrocnemius and plantaris muscles were also assessed by hematoxylin and eosin staining. In results, The muscles from ethanol treated rats displayed a significant reduction in muscle weight and average cross section area compared to Normal group. Daekumeumja extract treated group showed increased muscle weight and muscle fiber compared to the ethanol treated group. It was concluded that Daekumeumja extract showed ameliorating effects on chronic alcohol myopathy in skeletal muscle.

흰쥐의 알코올 유발성 간손상에 실비음(實脾飮)이 미치는 보호 효과

김범회 한방비만학회 2018 한방비만학회지 Vol.18 No.2

Objectives: The objective of this study is to investigate the effects of Silbi-um (SBU) extract on the alcoholic fatty liver induced by EtOH administration for 8 weeks. Methods: Male Sprague Dawley rats were used. All animals were randomly divided into 3 groups; Normal, EtOH and EtOH+SBU. The rats of EtOH group were daily treated with ethanol of 25% (v/v) for 8 weeks (n=10). EtOH+SBU group was orally treated with SBU water extract after ethanol administration (n=10). The rats of Normal group were treated with saline (n=10). After 8 weeks, the mean body weight, liver weight, and liver-body weight ratio were calculated. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of all groups were measured. The morphological alterations were observed using hematoxylin and eosin (H&E) and Oil Red O staining. Moreover, the alteration of tumor necrosis factor-α (TNF-α) levels were analyzed immunohistochemistrically. Results: The histological data showed that liver sections from EtOH group displayed severe steatosis. SBU extract significantly inhibited the progression of the alcoholic liver injury. The increased serum level of ALT and AST induced by ethanol administration were decreased by SBU extract. Furthermore, SBU extract significantly decreased the liver concentrations of TNF-α. Conclusions: SBU water extract attenuated the alcohol induced fatty liver by improving hepatic lipid metabolism via suppression of TNF-α protein. SBU could be effective in protecting the liver from alcoholic fatty liver.