Changes in the Muscarinic Receptors on the Colonic Smooth Muscles of Rats with Spinal Cord Injury

주민철,김용성,최을식,오정택,Hyun Joon Park,이문영 대한재활의학회 2011 Annals of Rehabilitation Medicine Vol.35 No.5

Objective To investigate changes in (1) the colonic response to acetylcholine (Ach), (2) the muscarinic (M)receptors in the colon, and (3) the levels of colonic contraction-related proteins after a spinal cord injury (SCI). Method We divided 16 Sprague-Dawley rats into 2 groups: the control group and the SCI group. A spinal cord transection was performed surgically at the T10 vertebral level. After 1 week, the entire colon was divided into 2segments, the proximal and distal colon. Each segment was mounted in a longitudinal or circular muscle direction in a 10-ml organ bath. We determined the intergroup differences as percentage changes in contractility after Ach treatment alone, Ach treatment with M2 receptor antagonist (AQ-RA741) pretreatment, and Ach treatment with M3 receptor antagonist (4-DAMP) pretreatment. Western blot analyses were performed to determine the expression level of RhoA, and heat shock protein 27 (HSP27). Results Compared to the control rats, the SCI rats showed an increased response to Ach along both the directions in the proximal colon (p<0.05). Compared to the control group, in the SCI group, the Ach response was signifi cantly diff erent in the proximal segment under AQ-RA741 pretreatment (p<0.05) and in the distal segment under 4-DAMP pretreatment (p<0.05). Findings of the western blot analyses showed a signifi cant decrease in the level of protein gene product 9.5 in the proximal and distal colon and a signifi cant increase in the level of RhoA and HSP27 in the proximal colon of the SCI rats. Conclusion Our results suggest that changes in colonic contractility after SCI are partly attributable to changes in the M receptor subtypes.

흰쥐에서 급성 구속 스트레스에 의해 유발된 식이억제에 대한 DA-9701의 효과

김용성,이문영,박종설,최을식,김민섭,박성훈,류한승,최석채 대한상부위장관ㆍ헬리코박터학회 2018 Korean Journal of Helicobacter Upper Gastrointesti Vol.18 No.1

Background/Aims: Stress has a role in the pathogenesis of functional dyspepsia (FD) and influences food intake in humans and animals. Prokinetic drugs have been used in FD, and some of these drugs reverse the feeding inhibition (FI) induced by acute restraint stress in rats. We aimed to evaluate the effect of DA-9701 on FI induced by acute restraint in rats. Materials and Methods: Male Sprague-Dawley rats were divided into 6 groups: Control (no stress), Stress+vehicle, and Stress+DA-9701 at doses of 1, 3, 10, and 30 mg/kg (n=6∼7). DA-9701 or vehicle was administered through gastric gavage 45 minutes before stress. After 60 minutes of stress, pre-weighed chow was given and the weight of remaining food was measured 30 and 60 minutes later. The effect of DA-9701 on FI was compared after pretreatment with WAY100635, a 5HT1A antagonist. Results: The restraint stress group had significantly less food intake than the control group. After feeding, rats given 1 and 3 mg/kg of DA-9701 showed increased food intake at 60 minutes, but this was not statistically significant. Rats given 10 mg/kg of DA-9701 showed significantly increased food intake at 30 minutes and 60 minutes (P<0.05). Interestingly, rats given 30 mg/kg of DA-9701 showed a significant decrease in food intake, similar to that of the vehicle group. The beneficial effect of 10 mg/kg of DA-9701 on FI was abolished by the pretreatment with WAY100635. Conclusions: Acute restraint stress reduced food intake in rats and pretreatment with DA-9701 improved stress-induced FI.

Radiolabeled Chitosan Hydrogel Containing VEGF Enhances Angiogenesis in a Rodent Model of Acute Myocardial Infarction

김대응,정환정,이창문,김남호,이삼윤,이문영,최을식,박순아,김창근,황효숙,임석태,손명희 한국고분자학회 2014 Macromolecular Research Vol.22 No.3

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis in an infarcted myocardium. The purpose of the current investigation was to validate whether a radiolabeled VEGF delivery system can beeffectively monitored in vivo, and to ascertain whether the growth factor induces an angiogenic effect to facilitaterecovery from infarct conditions in rodent myocardial infarction (MI) models. Rat MI models were divided intothree groups, one with left anterior descending coronary artery (LAD) ligation with no injection (the control group),one with LAD ligation and I-131 VEGF injection (the VEGF group), and one with LAD ligation and I-131 VEGF-loadedchitosan injection (the VIC group). On day 7 after injection, autoradiography imaging was performed, followed by semiquantitativeand histopathologic analyses. In semi-quantitative analysis, the mean anterior-to-inferior wall ratio of the VICgroup was significantly higher than those of the control and VEGF groups (p<0.05). Histopathologic experimentsrevealed a marked increase in microvascular density in the VIC group compared to those of the control and VEGF groups(p<0.05). Intramyocardially injected VIC was not only effectively monitored in vivo, but also stimulated therapeuticangiogenesis in the infarcted myocardium. Our findings support that the developed VIC is a novel theranostic toolto improve myocardial perfusion following myocardial infarction.

심근경색 모델 흰쥐에서 스트레스가 B-type Natriuretic Peptide 발현 및 심박변이율 변화에 미치는 영향

이삼윤(Sam Youn Lee),이미경(Mi Kyoung Lee),김남호(Nam-ho Kim),주민철(Min Cheol Joo),조항정(Hyang Jeong Jo),강지숙(Ji Sook Kang),김병숙(Byung Sook Kim),윤선식(Sun Sik Yoon),최을식(Eul Sig Choi),이문영(Moon Young Lee) 대한스트레스학회 2010 스트레스硏究 Vol.18 No.3

심박변이율의 감소는 심근 경색 환자에서 예후의 악화와 관련되어 있다. 심박변이율 중 very low frequency가 심부전환자의 예후를 판단할 수 있는 독립적 인자로서 사용이 가능하다고 보고된 바 있으며, 심실의 압력 증가에 반응해서 생성되는 B-type natriuretic peptide가 심근 경색의 예후 인자로서 사용할 수 있음 역시 보고된 바 있다. 본 연구에서는 심근경색 모델을 제작하여 일정의 회복 기간을 거친 다음 다시 일정 기간의 스트레스를 겪게 한 후 심박변이율의 변화 및 심실 조직에서의 BNP 발현 정도를 비교하여 스트레스에 의한 영향을 관찰하고자 하였다. Sprague-Dawley계 수컷 흰쥐 15마리를 대상으로 하였다. 실험동물은 인위적 스트레스 및 수술을 받지 않은 대조군(CON, n=5), 심근경색 수술을 받은 후 restraint stress를 받지 않은 군(MI+No Stress, n=5), 심근경색 수술을 받은 후 1주일 동안 restraint stress를 받은 군(MI+Stress, n=5)으로 분류하였다. 심근경색 모델 제작 직후 15분 이상 심전도의 변화를 기록하였으며, 2개월 정도 후 심근경색 수술을 받은 동물을 두 군으로 나누어 그 중 한 군에는 1주일 동안 restraint stress를 가한 후 restraint stress를 가하지 않은 동물과 심박변이율을 비교 분석하였다. 심실 조직은 좌심실 전벽 부위의 위축을 관찰할 수 있었고, 대식세포에 의하여 응고, 괴사된 심근세포의 탐식과 혈관이 풍부한 육아조직 및 섬유 변화를 볼 수 있었다. 심박변이율은 심근경색 수술을 받은 직후 심박수는 유의한 증가를 보였고, standard deviation of the normal to normal intervals (SDNN), very low frequency (VLF) 및 low frequency (LF)의 유의한 감소를 보였다. 심근경색 수술을 받았던 동물에서 두 달 정도의 회복 기간을 거친 후 스트레스를 받지 않은 군은 심박수 및 기타 심박변이율 분석에서 SDNN 값을 제외하고는 정상군과 유의한 차이를 관찰할 수 없었던 반면 1주일 동안 스트레스를 받은 군에서는 심박수가 다시 유의하게 증가했을 뿐만 아니라 SDNN, VLF 및 LF 역시 정상군과 유의한 차이를 보였다. 이상의 결과를 종합하면 심근경색 동물에 대해 1주일 동안 스트레스를 가한 결과 심박변이율이 감소하고 심실에서의 BNP 발현은 더욱 증가하여 악화함을 보여주고 있다. Diminished heart rate variability (HRV) is associated with less favorable prognosis after myocardial infarction (MI). It has been reported that very low frequency (VLF) power in HRV analysis is an independent risk predictor in patients with congestive heart failure and B-type natriuretic peptide (BNP) can be used as a prognostic factor of MI. The purpose of this study was to investigate whether stress has an effect to the changes of BNP expression and/or heart rate variability in MI model in rats. Male Sprague-Dawley rats were divided into 3 groups: control group (CON), MI group (MI+No Stress), and MI followed by stress group (MI+Stress). MI+Stress group rats were raised for a two month recovery period after the operation, followed by being exposed to restraint stress for 2 hours per day for 1 week. Electrocardiogram was recorded after the operation and the last day after 1 week of stress. The frequency components of HRV were calculated in the frequency domain such as VLF, low frequency (LF), high frequency (HF) and so on. In HRV analysis, standard deviation of the normal to normal intervals (SDNN) was significantly reduced in both groups compared to the control group. VLF and LF also were significantly reduced in MI+Stress group compared to the control groups. In addition, BNP expression in western blotting was shown the strongest bands in MI+ Stress group among experimental groups. These results suggest that BNP and HRV were aggravated by stress in MI rat model. (Korean J Str Res 2010;18:275∼285)