[학위논문]大柴胡湯이 diethylnitrosamine으로 유발된 흰쥐의 간암에 미치는 영향 (The) effect of Daeshiho-tang(DS) on hepatocellular carcinogenesis induced by diethylnitrosamine(DENA) in rats원문보기
간암은 우리나라 40-50대 남자의 주요한 사망 원인이며 인구 10만명 당 남자는 33.9명 여자는 10.9명이 간암으로 사망하고 있다1). 일반적으로 간암의 위험 인자로는 간경화증과 같은 만성 간질환을 들 수 있으며, 우리나라에서는 B형 및 C 형 간염 바이러스, 알코올 등도 주요 위험 인자로 알려져 있다2). 현재 간암에 대한 서양의학적 치료는 수술요법, ...
간암은 우리나라 40-50대 남자의 주요한 사망 원인이며 인구 10만명 당 남자는 33.9명 여자는 10.9명이 간암으로 사망하고 있다1). 일반적으로 간암의 위험 인자로는 간경화증과 같은 만성 간질환을 들 수 있으며, 우리나라에서는 B형 및 C 형 간염 바이러스, 알코올 등도 주요 위험 인자로 알려져 있다2). 현재 간암에 대한 서양의학적 치료는 수술요법, 방사선요법, 화학요법 등이 주가 되고 있으나, 암세포주에 대한 직접적인 살상을 목표로 하고 있기 때문에 세포독성 효과는 있지만 대부분 개체저항력을 떨어뜨리는 부작용이 있어, 최근에는 부작용이 적은 생약과 복합처방이 연구대상이 되고 있다3,4). 한의학에서는 현대에 이르러 서양의학적인 개념이 도입됨으로써 간암에 대한 새로운 인식과 실험적 연구가 진행되어, 단일약물의 간암에 대한 효과에 대해서는 한5)등은 楡根皮 抽出液, 원6)은 紅花藥針液, 류7)등은 녹용약침을 이용한 연구를 보고하였으며, 복합제약물의 간암에 대한 효과에 대해서는 김8)등은 茵蔯淸肝湯, 이9)등은 茵蔯蒿湯이 추출액을 이용한 연구를 보고하였다. 대시호탕은 東漢代 張仲景의 <傷寒論>11)에 처음으로 수록되었으며 小柴胡湯에 承氣湯을 합하여 加減되어 있어 外解少陽 內瀉熱結 疏肝解鬱 등의 효능이 있다12,13). 기존의 대시호탕에 대한 실험적 연구로는 홍14)등은 血管 肝毒性, 利膽 및 抗糖尿效果에 對하여, 김15)등은 acetaminophen으로 유도된 간독성 흰쥐에 미치는 영향을, 정16)등은 CCl4 및 d-galactosamine으로 유발된 흰쥐의 肝損傷에 미치는 影響을 보고하여 대시호탕이 간손상에 유효한 효과가 있음을 실험적 보고하였으나 대시호탕이 간암에 미치는 영향에 대한 실험적 연구는 아직 보고가 미비한 실정이다. 이에 저자는 대시호탕의 간암 형성 및 진행과정에 대한 항암효과를 구명하기 위하여 간암유발물질로 알려져 있는 diethylnitrosamine(DENA)17)을 이용하여 흰쥐에 간암을 유발시킨 후, 체중과 간 중량의 변화, Transaminase(AST, ALT)의 활성, Alkaline phosphatase(ALP)와 Lactate dehydrogenas(LDH)의 활성, AFP의 농도, 항산화효소 (SOD, catalase)의 활성, 간조직의 육안적, 광학현미경 관찰, 면역조직화학, 전자현미경 관찰 등을 통해 유의성 있는 결과를 얻었기에 보고하는 바이다.
간암은 우리나라 40-50대 남자의 주요한 사망 원인이며 인구 10만명 당 남자는 33.9명 여자는 10.9명이 간암으로 사망하고 있다1). 일반적으로 간암의 위험 인자로는 간경화증과 같은 만성 간질환을 들 수 있으며, 우리나라에서는 B형 및 C 형 간염 바이러스, 알코올 등도 주요 위험 인자로 알려져 있다2). 현재 간암에 대한 서양의학적 치료는 수술요법, 방사선요법, 화학요법 등이 주가 되고 있으나, 암세포주에 대한 직접적인 살상을 목표로 하고 있기 때문에 세포독성 효과는 있지만 대부분 개체저항력을 떨어뜨리는 부작용이 있어, 최근에는 부작용이 적은 생약과 복합처방이 연구대상이 되고 있다3,4). 한의학에서는 현대에 이르러 서양의학적인 개념이 도입됨으로써 간암에 대한 새로운 인식과 실험적 연구가 진행되어, 단일약물의 간암에 대한 효과에 대해서는 한5)등은 楡根皮 抽出液, 원6)은 紅花藥針液, 류7)등은 녹용약침을 이용한 연구를 보고하였으며, 복합제약물의 간암에 대한 효과에 대해서는 김8)등은 茵蔯淸肝湯, 이9)등은 茵蔯蒿湯이 추출액을 이용한 연구를 보고하였다. 대시호탕은 東漢代 張仲景의 <傷寒論>11)에 처음으로 수록되었으며 小柴胡湯에 承氣湯을 합하여 加減되어 있어 外解少陽 內瀉熱結 疏肝解鬱 등의 효능이 있다12,13). 기존의 대시호탕에 대한 실험적 연구로는 홍14)등은 血管 肝毒性, 利膽 및 抗糖尿效果에 對하여, 김15)등은 acetaminophen으로 유도된 간독성 흰쥐에 미치는 영향을, 정16)등은 CCl4 및 d-galactosamine으로 유발된 흰쥐의 肝損傷에 미치는 影響을 보고하여 대시호탕이 간손상에 유효한 효과가 있음을 실험적 보고하였으나 대시호탕이 간암에 미치는 영향에 대한 실험적 연구는 아직 보고가 미비한 실정이다. 이에 저자는 대시호탕의 간암 형성 및 진행과정에 대한 항암효과를 구명하기 위하여 간암유발물질로 알려져 있는 diethylnitrosamine(DENA)17)을 이용하여 흰쥐에 간암을 유발시킨 후, 체중과 간 중량의 변화, Transaminase(AST, ALT)의 활성, Alkaline phosphatase(ALP)와 Lactate dehydrogenas(LDH)의 활성, AFP의 농도, 항산화효소 (SOD, catalase)의 활성, 간조직의 육안적, 광학현미경 관찰, 면역조직화학, 전자현미경 관찰 등을 통해 유의성 있는 결과를 얻었기에 보고하는 바이다.
This study was designed to investigate the effect of Daeshiho-tang on hepatocellular carcinogenesis in rats. Sprague Dawley(SD) rats of control and experimental groups received intraperitoneal injection of 50 ㎎/㎏ DENA, weekly for 12 weeks. Experimental groups were divided into two, 4th and 8th week ...
This study was designed to investigate the effect of Daeshiho-tang on hepatocellular carcinogenesis in rats. Sprague Dawley(SD) rats of control and experimental groups received intraperitoneal injection of 50 ㎎/㎏ DENA, weekly for 12 weeks. Experimental groups were divided into two, 4th and 8th week group, and subdivided into four; normal group (Nor), hepatocellular carcinogenesis inducing control group (Con), and DS extract 250㎎/㎏/day (DSA) or 750㎎/㎏/day (DSB) administered groups to Con. Thereafter the changes of the body weight, the liver weight and the weight of liver/100g body weight, the activities of AST, ALT, ALP, LDH, AFP, SOD were measured. And we observed by gross anatomy, optical and electron microscopy. The results were as follows, In the 4th week group : The body weight was increased in DSA, DSB groups compared with Con. The weight of liver was significantly decreased in DSA, DSB compared with Con and the weight of liver/100g body weight was significantly decreased in DSA compared with Con. The activities of AST were significantly decreased in DSB compared with Con. The activities of ALT, AFP and SOD were decreased in DSA, DSB compared with Con. But there was not statistically significant. The activities of ALP were significantly decreased in DSA, DSB compared with Con. The activities of LDH were decreased in DSB compared with Con. But there was not statistically significant. According to the gross anatomical observation, we observed that DSB improved than Con in morphological changes. The size and numbers of the hepatic p53 positive cells were decreased in DSB compared with Con. According to the optical and electron microscopical observation, DSA, DSB were improved than Con in morphological and histopathological changes. In the 8 weeks group : The body weight was increased in DSA, DSB compared with Con. The weight of liver was decreased in DSA, DSB compared with Con. But there was not statistically significant. The weight of liver/100g body weight was significantly decreased in DSA compared with Con. The activities of AST, ALT and AFP were decreased in DSA, DSB compared with Con. But there was not statistically significant. The activities of ALP were significantly decreased in the DSA, DSB compared with Con. The activities of LDH were significantly decreased in DSA compared with Con. The activities of SOD were increased in DSB compared with Con. But there was not statistically significant. According to the gross anatomical observation, we observed that DSA, DSB improved than control group in morphological changes. The size and numbers of the hepatic p53 positive cells were decreased in DSA, DSB compared with control group. According to the optical and electron microscopical observation, DSA, DSB were improved than Con in morphological and histopathological changes. The results of this study showed a significant effect. It can be estimated that Daeshiho-tang has some effects on hepatocellular carcinogenesis induced by DENA in Rats, and further studies will be needed. Key words : Hepatocellular Carcinogenesis, Daeshiho-tang Diethylnitrosamine(DENA),
This study was designed to investigate the effect of Daeshiho-tang on hepatocellular carcinogenesis in rats. Sprague Dawley(SD) rats of control and experimental groups received intraperitoneal injection of 50 ㎎/㎏ DENA, weekly for 12 weeks. Experimental groups were divided into two, 4th and 8th week group, and subdivided into four; normal group (Nor), hepatocellular carcinogenesis inducing control group (Con), and DS extract 250㎎/㎏/day (DSA) or 750㎎/㎏/day (DSB) administered groups to Con. Thereafter the changes of the body weight, the liver weight and the weight of liver/100g body weight, the activities of AST, ALT, ALP, LDH, AFP, SOD were measured. And we observed by gross anatomy, optical and electron microscopy. The results were as follows, In the 4th week group : The body weight was increased in DSA, DSB groups compared with Con. The weight of liver was significantly decreased in DSA, DSB compared with Con and the weight of liver/100g body weight was significantly decreased in DSA compared with Con. The activities of AST were significantly decreased in DSB compared with Con. The activities of ALT, AFP and SOD were decreased in DSA, DSB compared with Con. But there was not statistically significant. The activities of ALP were significantly decreased in DSA, DSB compared with Con. The activities of LDH were decreased in DSB compared with Con. But there was not statistically significant. According to the gross anatomical observation, we observed that DSB improved than Con in morphological changes. The size and numbers of the hepatic p53 positive cells were decreased in DSB compared with Con. According to the optical and electron microscopical observation, DSA, DSB were improved than Con in morphological and histopathological changes. In the 8 weeks group : The body weight was increased in DSA, DSB compared with Con. The weight of liver was decreased in DSA, DSB compared with Con. But there was not statistically significant. The weight of liver/100g body weight was significantly decreased in DSA compared with Con. The activities of AST, ALT and AFP were decreased in DSA, DSB compared with Con. But there was not statistically significant. The activities of ALP were significantly decreased in the DSA, DSB compared with Con. The activities of LDH were significantly decreased in DSA compared with Con. The activities of SOD were increased in DSB compared with Con. But there was not statistically significant. According to the gross anatomical observation, we observed that DSA, DSB improved than control group in morphological changes. The size and numbers of the hepatic p53 positive cells were decreased in DSA, DSB compared with control group. According to the optical and electron microscopical observation, DSA, DSB were improved than Con in morphological and histopathological changes. The results of this study showed a significant effect. It can be estimated that Daeshiho-tang has some effects on hepatocellular carcinogenesis induced by DENA in Rats, and further studies will be needed. Key words : Hepatocellular Carcinogenesis, Daeshiho-tang Diethylnitrosamine(DENA),
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