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소화관 기계적 폐쇄에 따른 Interstitial Cells of Cajal (ICC) 및 위장관운동의 변화
전제열(Jae-Yeoul Jun),정춘해(Choon-Hae Chung),유호진(Ho-Jin You),김경희(Kyung-Hee Kim),김장만(Jang-Man Kim),김기훈(Kee-Hune Kim),박도영(Do-Young Park),장인엽(In-Youb Chang) 대한해부학회 2002 Anatomy & Cell Biology Vol.35 No.5
Interstitial cells of Cajal (ICC)는 내장 민무늬근세포와 소화관 신경종말들과 밀접한 해부학적 연관성을 가지고 있으며, ICC가 소화관 연동운동에 있어서 소화관 연동운동의 향도잡이 역할을 할 뿐만 아니라, 소화관신경으로부터 민무늬근세포로 전해지는 신경전달을 매개, 조절한다고 알려져 있다. 최근 여러 소화관운동장애 질환에서 ICC의 감소 및 소실이 병인과 연관성이 있다는 주장들이 제기되는 실정이다. 이에 따라 저자들은 수술적으로 생쥐 작은창자를 부분폐쇄를 시킨 다음, 작은창자 근육층의 비대증을 유도한 후 소화관 운동의 변화 및 ICC의 형태학적 변화를 밝혀내고자 ICC에 대한 면역형광염색과 전기생리학적 실험을 병행하여 실시하였다. 작은창자를 부분폐쇄시키고 2주 후, 폐쇄부위보다 입쪽의 작은창자부위에서 육안적으로 창자의 직경이 증가하고, 광학현미경적으로 근육층의 비대가 나타나는 것을 관찰할 수 있었다. ICC에 대한 면역형광염색(c-kit staining) 결과, ICC 그물망이 폐쇄부위보다 입쪽으로 25 mm 정도까지 소실 또는 뚜렷하게 감소되는 것을 관찰할 수 있었으며, 이러한 형태학적 결과와 병행하여 전기생리학적으로도 서파의 소실 또는 감소가 나타남을 관찰할 수 있었다. 그러나 폐쇄부위보다 항문쪽에서는 ICC와 서파의 이상소견은 관찰되지 않았다. 본 실험 결과 소화관의 폐쇄에 따라 입쪽부위 ICC의 소실과 서파의 소실을 관찰할 수 있었다. 따라서 앞으로 ICC 구조를 변화하게 하는 분자생물학적 그리고 유전학적 신호체계에 대해 면밀한 분석을 할 경우 소화관운동장애의 발생원인 및 치료에 계기를 마련할 수 있을 것으로 사료된다. Interstitial cells of Cajal (ICC) are the pacemakers in gastrointestinal slow wave, and also transduce signal inputs from the enteric nervous system to smooth muscle. The abnormal motility corresponded to a lack or decreasing of ICC and a disruption of electrical slow waves. So we developed partial obstruction model in murine small intestine and investigated changes in the ICC networks and electrical activity in the obstructed bowel using c-kit immunohistochemistry and intracelluar electrophysiological techniques. Two weeks following the onset of a partial obstruction, the small intestine increased in diameter and muscular hypertrophy was developed oral to the obstruction site. ICC were absent or only weak at 1~25 mm oral to the occlusion site, and this disruption was accompanied by the loss of electrical slow wave. ICC networks and slow waves were normal appearance aboral to the clip. In conclusion, The present results showed that partial intestinal obstruction induced the loss of ICC networks and slow waves. These result will provide a valuable aid for understanding pathogenesis of intestinal motility disorder, and this model may be an important tool for evaluating genetic or molecular factor for the therapeutic opportunities of motility disorder in human.
개의 출생 후 중추신경계통 발달에서 Platelet-derived growth factor α-receptor (PDGF-αR)의 발현
윤상필(Sang-Pil Yoon),전제열(Jae-Yeoul Jun),유호진(Ho-Jin You),김주영(Joo-Young Kim),양경철(Kyung-Chul Yang),안병수(Byung-Soo Ahn),장인엽(In-Youb Chang) 대한해부학회 2003 Anatomy & Cell Biology Vol.36 No.1
Platelet-derived growth factor (PDGF)는 민무늬근육세포, 섬유모세포, 아교세포 등의 분열능력에 상당한 영향을 미치고, 세포의 분열 및 분화의 유도, 조직손상의 복구, 염증, 종양형성 등에 관여하며, 신경계통에서는 주로 아교세포계열의 발생에 중요한 기능을 수행하는 것으로 알려져 왔다. 배자의 출생 후 발달중인 신경원에는 PDGF-αR가 존재하지 않는다는 주장들이 대부분이고, 또 PDGF-αR이 성숙한 신경원에 존재한다는 최근 보고는 생쥐의 신경원에서 밝혀냈을 뿐이다. 따라서 고등포유동물인 개의 중추신경계통에서 출생 후 발달에 따른 PDGF-αR양성신경원의 존재 양상을 밝혀내고자 면역조직화학염색을 실시하여 다음과 같은 결과를 얻었다. 대뇌겉질의 속피라밋층, 해마와 치아이랑의 피라밋세포 및 과립세포, 줄무늬체의 창백핵, 조가비핵, 꼬리핵, 시상의 배쪽앞쪽핵, 그물핵, 가쪽무릎체, 뒤쪽시상하부핵, 흑색질, 얼굴신경핵, 안뜰핵, 삼차신경핵 등의 뇌줄기핵, 소뇌의 조롱박세포와 과립세포, 척수의 뒤뿔과 앞뿔 등 여러 부위에서 출생 0일부터 PDGF-αR의 염색반응을 보이는 신경원들을 관찰할 수 있었는데, 이들은 출생 후 6개월까지 지속적으로 관찰되었다. PDGF-αR의 염색반응양상은 대체로 출생 후 1개월까지 세포의 가지돌기 및 축삭에 잘 표지되었지만, 그 이후 신경세포의 염색성과 숫자가 감소되는 경향을 보이며, 출생 후 6개월까지 발현을 확인할 수 있었다. 이상의 실험결과로 미루어 출생 후 6개월까지 발달과정동안 개 중추신경계통에서 PDGF-αR양성신경원이 지속적으로 존재한다는 것을 알 수 있었으며, 이로서 PDGF가 중추신경계의 특정부위에 있는 신경원의 성숙에 관여한다고 사료된다. Platelet-derived growth factor (PDGF) was initially described for its mitogenic activity on smooth muscle cells, fibroblast, and glial cells. The biological activities of PDGF include stimulation of mitogenesis, differentiation, wound healing, inflammation, and tumor formation. The localization of platelet-derived growth factor-α receptor (PDGF-αR) in central nervous system was commonly restricted to oligodendrocyte progenitors during late embryonic and postnatal development. However, several studies recently demonstrated that postnatal neurons could also synthesize PDGF-αR in rodents. In the present study, to analyze the distributional pattern of PDGF-αR during postnatal development of the canine CNS, we used immunohistochemical method on sections of canine brain tissue. We found that neurons of various CNS regions, including cerebral cortex, striatum, diencephalon, nuclei of brain stem, cerebellum, spinal cord, exhibited the immunoreactivity to PDGF-αR as early as postnatal day 0. Generally PDGF-αR immunoreactivity was well localized in the dendrites and axons of neuron during the postnatal day 14 and postnatal day 28, and then showed diminished pattern. But neuronal immunoreactivity to PDGF-αR were maintained postnatal 6 month. These results suggest that the localization of PDGF-αR in postnatal developing neurons supports the several roles of PDGF for neurons including maturation and survival.
신성고혈압 흰쥐에서 5-HT에 의한 혈관수축에 있어 Tyrosine Kinase의 역할
염철호(Cheol Ho Yeum),전제열(Jae Yeoul Jun),윤평진(Pyung Jin Yoon),김재훈(Jai Hun Kim),김종승(Jong Seung Kim),이정희(Jeong Hoe Liee) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.1
N/A Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. The involvement of tyrosine kinases in 5-hydroxytryptamine (5-HT)-induced contractile response of the isolated aorta was examined in two-kidney, one clip (2K1C) hypertensive rats, 2141C hypertension was made by constricting the left renal artery and age-matched control rat received sham treatment. Thoracic aortic rings denuded of endotheliurn were mounted in tissue bath, for measurement of isometric contractile force. The putative tyrosine kinase inhibitor, genistein, shifted concentration-response curves to 5-HT toward the right in control rats The isometric force generation induced by 5-HT was also inhibited by genistein in aortic rings from 2K1C: hypertensivc rats, however genistein did not affect on the high concentration of 5-HT in hypertensive rat ;. Genistein-induced relaxations were more attenuated in aortae from hypertensive rats than those from control Genistein had no effect on contrartcion elicited by the direct protein kinase C activator, phorbol 12, 13 dibutyrate (PDBu) either in 2KlC hypertensive or in control Group. These findings indicate that genistein-sensitive tyrosine kinases paeticipate in 5-HT-induced contraction of rat aortic smooth muscle, of which role is apparent in 2K1C: hypertension.
신혈관성 고혈압쥐에서 Atrial Natriuretic Peptide가 혈관 기초장력에 미치는 영향
최석 ( Seok Choi ),김명룡 ( Myung Young Kim ),조남수 ( Nam Soo Cho ),선재명 ( Jae Myung Sun ),위희욱 ( Hee Wook Whi ),전제열 ( Jae Yeoul Jun ),윤평진 ( Pyung Jin Yoon ),정종훈 ( Jong Hoon Chung ),염철호 ( Cheol Ho Yeum ) 대한신장학회 2008 Kidney Research and Clinical Practice Vol.27 No.5
Purpose: Hypertension may be involved an alteration of intrinsic basal tone in vascular smooth muscle. The purpose of this study was to investigate the vasorelaxant effect of atrial natriuretic peptide (ANP) on isolated non-contracted aorta from two-kidney, one clip (2K1C) renovascular hypertensive rats. Methods: 2K1C hypertension was induced by clipping the left renal artery and were used 6 weeks later. Age-matched rats receiving a sham treatment, which served as controls. The thoracic aortae were mounted in tissue baths to measure the isometric tension. Results: ANP diminished basal tone in previously unstimulated thoracic aortic rings from 2K1C hypertensive rats, while it had no effect in the control rats. Endothelial destruction potentiated the vasorelaxant effect of ANP on basal tone in 2K1C rats. A similar potentiation of the ANP response was observed by pre-treatment with Nω-nitro-L-arginine methyl ester (L-NAME) or methylene blue in aortic rings with endothelium. Treatment with calcium-free Krebs decreased basal tone and abolished ANP-response. These effects were observed only in aortic rings from 2K1C rats. Similarly, staurosporine and calphostin C, inhibitors of protein kinase C (PKC), lowered basal tone and abolished ANP-response in hypertensive rats. Conclusion: These results demonstrate that ANP has a vasorelaxant effect on basal tone in 2K1C renovascular hypertension. Inhibition of ANP effects on basal tone by calcium-free Krebs and PKC antagonists suggests that altered Ca2+-active tone is involved in hypertension, that modifies the response of vascular smooth muscle to the ANP.
신성 고혈압 쥐에서 Pinacidil에 의한 혈관 이완반응에 있어 산소유리기의 역할
염철호 ( Cheol Ho Yeum ),최석 ( Seok Choi ),유임준 ( Im Joon Yoo ),위희욱 ( Hee Wook Whi ),전제열 ( Jae Yeoul Jun ),김현일 ( Hyun Il Kim ),신혜랑 ( Hye Rang Shin ),오현정 ( Hyun Jung Oh ),정종훈 ( Jong Hoon Chung ) 대한신장학회 2010 Kidney Research and Clinical Practice Vol.29 No.6
Purpose: Evidence has emerged that oxygen-derived free radicals may induce vascular relaxations via ATP-sensitive K+ (KATP) channels and the level of free radicals is increased in animal models of hypertension. The present study was conducted to determine whether relaxations to an KATP channel opener, pinacidil, are increased in the aorta from two-kidney, one clip (2K1C) hypertensive rats and whether free radial scavengers reduce these relaxations. Methods: 2K1C hypertension was induced by clipping the left renal artery and age-matched control rats received a sham treatment. Rings of aortae without endothelium were suspended for isometric force recording. Results: Relaxations to pinacidil (10-8 to 10-5 M), which are abolished by glibenclamide (10-5 M), were augmented in the aorta from 2K1C rats, compared to those from control rats. In the aorta from 2K1C rats, catalase (1,200 U/mL), but neither superoxide dismutase (150 U/mL) nor deferoxamine (10-4 M), reduced relaxations to pinacidil, whereas in the aorta from control rats, the free radical scavengers did not affect these relaxations. Conclusion: These results suggest that in 2K1C hypertension, vasorelaxation to an KATP channel opener is augmented and that hydrogen peroxide in smooth muscle cells may partly contribute to these relaxations.