Telluric Acid가 흰쥐 간조직의 미세구조에 미치는 영향

손석주,정영길,조승묵,백태경,최창도,최월봉,Son, Serk-Joo,Jeong, Young-Gil,Cho, Seung-Muk,Baik, Tai-Kyung,Choi, Chang-Do,Choi, Wol-Bong 한국현미경학회 1995 Applied microscopy Vol.25 No.4

This experiment was carried out to investigate the effects of telluric acid on the histological and fine structural changes in the rat liver. Fischer 344 rats($150{\sim}200gm$) were used in this study as control and experimental groups. Telluric acid(5 mg/100 gm of body weight) suspensed in olive oil was given intraperitoneally to the animals of the experimental group and only olive oil to those of the control group. At the intervals of 3, 6 and 12 hours, 1, 2, 3, 5, 10, 20, 30 and 60 days after administration, the animals were sacrificed, and livers were obtained from the rats. For light microscopic examination of the liver, sections($5{\mu}m$) were stained with hematoxylineosin(H-E). For electron microscopic examination of the liver, sections were stained with uranyl acetate and lead citrate, finally examined with Zeiss EM 109 electron microscopes. The results obtained were as follows. 1. In the control group, round nucleus. well developed mitochondria, Golgi apparatus, rough endoplasmic reticulum(RER) and numerous glycogen particles were observed in the cytoplasm of the hepatocyte. In the cytoplasmic membranes of the hepatocyte, sinusoidal surface had numerous microvilli and cellular surface is combinated adjacent hepatocyte with desmosomes. The RER cisterns were dilated and zymogen granules were fewer than those of the dark cells. Kupffer cells with irregular nuclear membrane were observed. Fat storing cell and collagenous fiber bundle were observed in the Disse space. 2. Kupffer cell, inflammatory cells in the connective tissue of hepatic triad and lysosome were increased in the 3, 6, and 12 hour experimental group comparing with that of the control group. 3. In the 1 day experimental group, infiltration of inflammatory cells in interlobular connective tissue, dilatation of sinusoidal capillary and increasing of Kupffer cell were observed. Atropic change of hepatocyte and aggregation of glycogen particles in the cytoplasm of hepatocyte were observed. In this group, desmosome near bile canaliculi and collagenous fiber bundle in the Disse space were increased comparing with that of the 12 hours experimental group. In the 2 days experimental group, desmosome, lysosome, peroxisome and collagenous fiber bundle were increased comparing with that of the 1 day experimental group. Furthermore, lamellated bodies were also seen in the cytoplasm of the hepatocyte. 4. In 3 and 5 days experimental groups, transformations of hepatic cell cord and degeneration of the hepatocyte were markedly inclosed comparing with the all experimental groups. And damaged RER and mitochondria. collagenous fiber bundle were also inclosed comparing with that of the 2 days experimental group. Autophagosome and fat storing cells with large lipid droplets were also observed comparing with that of the 2 days experimental group. Tight junction and desmosome between the hepatocytes were separated. These degenerating changes were severe through the all experimental groups. 5. In the 10 and 20 days experimental groups, arrangement of hepatic cell cords and cell organelles of hepatocytes were similar to those of the control group. However, aggregation of glycogen particles, dilatation of sinusoidal capillary and infiltration of inflammatory cells remained. 6. In the 30 days experimental group, the tissue findings were similar to those of the control grout. But lamellated bodies in some hepatocytes and lysosome were remained in the cytoplasms of the Kupffer cells. In the 60 days experimental group, these all changes were recovered as the control group. In conclusion, telluric acid would directly induce the degenerative and necrotic changes on the hepatic tissue. However, these changes were perfectly recoverd in the 60 days experimental group as the control group.

상완, 중완, 하완 구요법과 사관 침요법의 혼합사용이 정상 백서 위 기능에 미치는 영향

한상묵(Sang Muk Han),황태준(Tae Jun Hwang),김홍재(Hong Jae Kim),정상구(Sang Gu Jung),조승묵(Seung Mook Jo),유윤조(Yun Cho Yu),김명동(Meyong Dong Kim) 한의병리학회 2005 동의생리병리학회지 Vol.19 No.5

Tissue Transglutaminase가 죽상동맥경화증 심장동맥에서 NF-kB 활성에 미치는 영향

김승오,김민경,서동현,김찬웅,조승묵,한장희,박정현,박경한,김대중,Kim, Seung-Oh,Kim, Min-Kyoung,Suh, Dong-Hyun,Kim, Chan-Woong,Cho, Seung-Muk,Hahn, Jang-Hee,Park, Jeong-Hyun,Park, Kyoung-Han,Kim, Dae-Joong 대한체질인류학회 2007 해부·생물인류학 (Anat Biol Anthropol) Vol.20 No.2

Tissue transglutaminase (tTGase)는 세포외기질 (extracellular matrix)의 유지를 위한 번역후수식 (post-translational modification) 작용과, 세포 안팎의 신호 전달체계에서 중요한 역할을 하는 것으로 알려져 있다. 본 연구에서는 죽상동맥경화의 발생 기전에서 nuclear factor-kB(NF-kB)의 활성에 미치는 tTGase의 영향을 조사하고자 하였다. 초기 및 고도의 죽상동맥경화증을 동반하는 한국인 40대 남성의 심장동맥을 대상으로 tTGase및 NF-kB 활성의 중요 요소인 I-kB (inhibitor of NF-kB)의 활성을 조직면역 염색으로 관찰하였다. 죽상동맥경화증의 진행에 따른 tTGase의 단백질 발현의 증가를 확인하였고, 고도로 진행된 혈관의 신생혈관내막(neointima)에서 I-kB의 활성이 증가하였다. 쥐의 심장근육세포로부터 유래된 세포주(H9c2)와 tTGase 단백질이 과발현된 세포주(H9c2/tTGase)를 대상으로 tTGase의 억제제를 이용하여 tTGase의 발현과 I-kB 인산화를 비교한 결과 tTGase가 I-kB의 인산화를 촉진시키는 결과를 얻었다. 본 실험을 통해 얻은 결과들은 tTGase와 NF-kB pathway의 활성기전 사이에 연관성이 있음을 시사하고 있으며, 심장동맥의 죽상동맥경화 발생기전에서 tTGase 단백질의 역할을 규명하는 작업의 바탕이 될 것이다. Molecular mechanism of nuclear factor-kB (NF-kB) in the atherosclerosis has been unclear. Recently, NF-kB activating function of tissue transglutaminase (tTGase), multifunctional calcium-dependent transamidation enzyme, have been reported in the various tissues like neuroglia. In this report, we investigated the immunoreactivity of tTGase at the human atherosclerotic coronary artery, and examined the effect of tTGase on the well-known proatherogenic NF-kB pathway using tTGase-overexpressed cells. Immunohistochemical studies on autopsy samples showed that immunoreactivity of tTGase was markedly elevated in the neointimal tissues of atherosclerotic coronary arteries with progression of disease. Immunohistochemical staining also demonstrated that phosphorylated I-kB was activated in the atherosclerotic vessel wall. In vitro study using rat cardiomyoblast (H9c2) and tTGase-overexpressed H9c2 showed that activated tTGase enhanced the phosphorylation of I-kB, and this activation was inhibited by tTGase specific inhibitors. These findings suggest that cytosolic tTGase may serve as an activator of NF-kB.

사람 심장동맥에서 죽상동맥경화증의 진행에 따른 활성 NF-κB 발현의 변화

신은경(Eun-kyung Shin),김민경(Min-kyung Kim),안준석(Jun-suk Ahn),김승오(Seung-oh Kim),이재학(Jae Hak Lee),박정현(Jeong Hyun Park),한장희(Jang Hee Hahn),조춘규(Chun-kyu Cho),조승묵(Seung-muk Cho),권태정(Tae-jeong Kwon),김대중(Dae-joon 대한해부학회 2006 Anatomy & Cell Biology Vol.39 No.2

혈관 민무늬근육세포의 증식은 동맥경화를 비롯한 증식성 혈관질환(proliferative vascular disease)의 발생 과정에서 중요한 부분을 담당하고 있다. 세포의 증식에 관여하는 여러 가지 원인들 중에서 nuclear factor-κB (NF-κB)의 작용이 중요한 것으로 알려져 있다. 그러나 민무늬근육세포의 증식에 있어서 NF-κB의 분자생물학적 작용기전은 아직 정확하게 밝혀지지 않은 실정이다. 본 연구에서는 한국인 40대 성인 남성의 왼심장동맥을 대상으로 죽상동맥경화증의 진행에 따른 NF-κB의 활성도 변화를 형광항체 염색을 이용하여 관찰하였다. 초기 병변을 보이는 혈관의 중간막 및 속막에서는 NF-κB가 활성화된 세포가 관찰되지 않았다. 중등도 병변에서는 신생혈관내막(neointima)에 위치하는 민무늬근육세포의 핵과, 죽상판(atheromatous plaque) 내부에 위치하는 큰포식세포들에서 NF-κB에 대한 양성반응이 관찰되었다. 병변이 고도로 진행된 혈관에서 활성 NF-κB는 신생혈관내막의 민무늬근육세포에서 중등도 병변에서 관찰되는 수준보다 광범위하게 관찰되었으며, 중간막을 구성하는 민무늬근육세포에서도 비교적 광범위하게 관찰되었다. NF-κB가 죽상동맥경화의 진행과 함께 민무늬근육세포에서 증가하는 결과는 죽상동맥경화의 발생 및 진행 과정에서 NF-κB가 중요한 역할을 담당하고 있음을 보여주고 있다. 따라서 본 연구의 결과는 혈관질환, 특히 증식성 혈관질환의 치료 방법 개발 측면에서 NF-κB가 중요한 대상이 될 수 있음을 시사한다. Paraffin sections of atherosclerotic vessels were classified into initial lesion, preatheroma and complicated severe lesion by classification method from American Heart Association. Activation of NF-κB was hardly detectable in the initial atherosclerotic lesion. In the preatheroma, activated NF-κB was enhanced in the neointimal smooth muscle cells and macrophages in the lipid core. In contrast, activated NF-κB increased markedly in the neointimal and medial smooth muscle cells in the severe atherosclerotic vessel wall. However, in the severe lesion, NF-κB activation was diminished in the macrophages of lipid core. Our findings show that NF-κB was activated in the smooth muscle cells with the progression of atherosclerosis in the human coronary artery.