Rat의 방사선 조사성 구내염에 대한 Recombinant Human Epidermal Growth Factor (rhEGF)의 효과

정권일(Kwonil Jung),김선희(Sunhee Kim),문수영(Soo Young Moon),김연화(Yeon Wha Kim),홍준표(Joon Pio Hong),김현숙(Hyun Sook Kim),이상욱(Sang-wook Lee) 대한방사선종양학회 2006 Radiation Oncology Journal Vol.24 No.1

목 적: 구내염은 두경부종양이 있는 암환자에게 방사선 및 항암제 치료 시술 시 매우 흔하게 발생하는 합병증이다. 본 연구는 Rat의 방사선성 구내염 모델에서 recombinant human epidermal growth factor (rhEGF)의 효과를 평가하 고자 하였다. 대상 및 방법: 25 Gy의 방사선량으로 두부에 단회 조사한 Rat를 무작위로 7마리씩 무처치군, 부형제 처치군, rhEGF 15 또는 30μg/day 구강 내 처치군으로 나누었으며, 방사선을 조사하지 않은 7마리의 Rat를 정상시험군으로 나누었다. rhEGF 시료 및 부형제는 1일 3회 Rat의 구강점막에 매일 도포하였다. Rat의 생존율, 체중변화 및 사료섭 취량을 18일 동안 관찰하였으며, 방사선 조사 후 7일 및 18일째에 Rat의 구강점막을 조직학적으로 평가하였다. 결 과: 실험종료 시점에서 rhEGF 15 또는 30μg/day 구강 내 처치군이 모두 33%의 생존율을 보인 것에 비하여,무처치군 및 부형제 처치군은 모두 0%의 생존율을 보였다. 체중변화에서도 rhEGF 처치군은 방사선 조사 후 2일부터 7일까지 부형제 처치군에 비하여 Rat의 평균체중이 통계적으로 더욱 무거웠다. 사료섭취율은 모든 시험군에서 방사선 조사 후 4일까지 감소하는 양상을 보이다가, rhEGF 15 또는 30μg/day 구강 내 처치군에서 14일째에 뚜렷한 사료섭취율의 증가가 관찰되었다. 방사선 조사 후 7일째의 조직학적 분석 결과, rhEGF 15 또는 30μg/day 구강내 처치군의 Rat에서는 점막 표피층의 각질세포의 종창 및 변성만이 관찰되었던 것에 비하여, 무처치군 및 부형제 처치군에서는 심한 위막성 또는 궤양성 구내염이 관찰되었다. 결 론: rhEGF (15 또는 30μg/day 구강 내 처치군) 처치에서 방사선 조사로 유발시킨 Rat의 구내염 모델에서 유의성 있는 치유 효과를 확인하였으며, 본 시험결과로 rhEGF가 방사선에 의해 유발된 구내염을 치료할 수 있는 임상제제로써의 가능성을 볼 수 있었다. Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGFtreated groups. Rats were topically applied with rhEGF (15 or 30μg/oral cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or 30μg/day) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

Human 성장호르몬을 도입한 Transgenic Rats의 작출과 번식표현형에 관한 연구 II. 형질전환된 Rats의 hGH수준이 번식표현형에 미치는 영향

장규태,김성현,성환후,주학진,박미령,윤창현 한국동물번식학회 1998 Reproductive & developmental biology Vol.22 No.2

The effects of continuous GH(hGH) secretion on the female reproduction was studies in adults female transgenic rats expressing the hGH gene with a mouse whey acid protein (mWAP) promotor. Two line of transgenic female rats carrying the mWAP/hGH gene were established and used in the study. One was characterized by relatively high levels of serum hGH (high line), and the other had relatively low levels (low line). 1. High line female rats had recurring, Pseudopregancy-like estrous cycles accompanied by increased serum progesterone level for 2 weeks after ovulation, and they were fertile. 2. In the rats, luteinization occurred spontaneously without cervical stimulation, probably due to high levels of serum hGH, which has prolactin (PRL)-like activity in the rat. 3. Low line female rats had recurring, regular 4-days estrous PRL surge following cervical stimulation were not, detected and PRL secretion was not induced by a dopamine antagonist. 4. The ovarian tissue in this line had a much higher number of corpora lutea and grew much heavier than in normal littermates, suggesting impairment of PRL induced structural luteolized. Su, pp.ession of PRL secretion in the low line rats was, at least in part, due to a marked decrease in the number of lactotrophs in the pituitary. The present study shows that the serum hGH level plays a crucial role in regulating luteal function in female transgenic rats expressing the hGH gene.

WHW®의 랫드에서의 반복경구투여 독성에 관한 연구

오태우,배효상,윤철호,박용기 대한본초학회 2010 大韓本草學會誌 Vol.25 No.3

Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity. Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

SD rats의 성별에 따른 형개 열수추출물의 방사선 방호효과

이지은(Ji-Eun Lee),김장오(Jang-Oh Kim),이윤지(Yoon-Ji Lee),전찬희(Chan-hee Jeon),허성회(Sung-Hoe Heo),민병인(Byung-In Min) 한국방사선학회 2021 한국방사선학회 논문지 Vol.15 No.3

본 연구는 형개 열수추출물이 흰 쥐의 성별에 따라 미치는 방사선 방호효과를 평가하는 것이다. 형개는 활성산소를 제거하는 대표적인 물질인 polyphenol과 flavonoid를 함유하고 있다. 이에 따라 방사선 방호효과를 알아보기 위해 형개 열수추출물을 SD rat 수컷과 암컷에 2 주 동안 경구투여 한 후 혈액학적 분석, 소장 융모 길이 변화 분석, SOD 활성 평가를 실시하였다. 수컷 SD rat ST+IR군은 IR군에 비해 혈소판의 회복능력이 조금 더 증가한 것으로 나타났다. 암컷 또한 ST+IR군이 IR군에 비해 혈소판 회복능력이 더 높게 나타났다. 림프구 수치도 혈소판 수치와 마찬가지로 수컷과 암컷 SD rat ST+IR군이 IR군보다 회복능력이 더 높게 나타났다. 방사선 조사 후 수컷 SD rat과 암컷 SD rat의 소장 융모 길이가 IR군보다 ST+IR군이 덜 감소한 것으로 보아 모든 성별의 SD rat 소장 융모가 손상이 적은 것을 확인하였다. 이 결과를 통해 형개 열수추출물이 방사선 방호효과가 있음을 확인 할 수 있었다. This study evaluates the radiation protection effects of Schizonepeta tenuifolia water extract on white rat by gender. Schizonepeta tenuifolia contains polyphenol and flavonoid, which are typical substances that remove free radical. Thus, to determine the effectiveness of radiation protection, the Schizonepeta tenuifolia water extract was administered to Sparaqu-Dawely (SD) rat males and females for two weeks, followed by hematological analysis, analysis of changes in the length of the small intestine villi length, and SOD activity evaluation. The male rat in ST+IR group showed a slightly greater recovery of platelets than the IR group. The ST+IR group also showed a higher platelet recovery capability than the IR group. lymphocyte showed that male and female rat ST+IR groups have higher resilience than IR groups likewise platelet. After irradiation, the villi length of the male rat and female rat decreased less in ST+IR group than in the IR group, indicating that the villi length of all genders was less damaged. This result confirmed that the Schizonepeta tenuifolia water extract had a radiation protection effect.

90% pancreatectomized rats 에서 w-6 다중불포화지방과 비타민 E 섭취가 인슐린 저항성에 미치는 영향

최수봉(Soo Bong Choi),박선민(Sun Min Park) 대한내과학회 1999 대한내과학회지 Vol.56 No.4

N/A High intake of -6 polyunsaturated fat (PUFA) can increase oxidative stress, which may in turn increase insulin resistance and be the cause of metabolic syndrome X (diabetes mellitus). One of the ways to reduce oxidative stress is through the consumption of antioxidants, such as vitamin E. However, it is controversial whether the consumption of vitamin E alleviates insulin resistance. The purpose of this study was to determine whether the excessive intake of -6 polyunsaturated fat and vitamin E influences the whole body glucose disposal rate (GDR), glycogen deposits in the liver and muscles, and the triglyceride content of muscles in 90% pancreatectomized rats. Methods : Mildly diabetic rats were produced by removing 90% of the pancreas from Sprague Dawley rats aged 8 weeks. One week after surgery, the blood glucose levels of rats were more than 9.4 mmol/L, according to which the rats are considered to be diabetic. Two factors were examined in the 90% pancreatectomized rats: polyunsaturated fat levels with 40% and 10% of total energy intakes, and vitamin E contents with 300 IU and 30 IU per kg of diet mixture. Four different diets were given for 8 weeks. After 7 weeks of diet consumption indwelling catheters were inserted in the carotid artery and jugular vein of all rats so that the GDR could be measured while the rats were awake and in a relaxed state. Results : Daily calorie and PUFA fat intake levels were higher in the high PUFA groups of diabetic rats. Daily vitamin E intake of the high vitamin E groups was ten times higher than that of the low vitamin E groups (p<0.0001). The GDR was lower in high PUFA groups, and the high intake of vitamin E tended to decrease the GDR in diabetic rats. The GDR of DHPHE was significantly lower than that of DLPLE (p<0.05). Sham operated rats (the control group) had a higher GDR by 44% than diabetic rats. Vitamin E deposits in the liver in DHPHE were higher in DLPLE (p<0.05). Glycogen deposits in the liver of diabetic rats were significantly higher in DLPLE than DHPLE. Muscle glycogen content showed a similar tendency to liver glycogen content in different diet groups of diabetic rats. Triglyceride deposits in muscles did not differ according to dietary fat and vitamin E contents in diabetic rats. Conclusions : High intake of -6 PUFA increased insulin resistance, and high vitamin E intake did not alleviate insulin resistance. Thus, increased oxidative stress may be an independent factor for increased insulin resistance in high intake of -6 PUFA. It is necessary to consume a minimum amount of -6 PUFA as well as the Recommended Daily Allowance of vitamin E.

STZ-당뇨쥐에서 운동부하가 골격근 및 간의 항산화효소 활성도에 미치는 영향

석광호,이석강 영남대학교 의과대학 2000 Yeungnam University Journal of Medicine Vol.17 No.1

당뇨쥐에서 운동부하가 골격근과 간의 항산화효소 활성도에 미치는 영향과 산소유리기에 의한 조직손상 여부를 관찰한 연구 결과를 요약하면 다음과 같다. Streptozotocin으로 유도한 당뇨군의 혈당농도(㎎/dL)는 344±14.8로서 대조군의 117±2.7보다 높았으며(p<0.001) 운동부하에 의해서 유의하게 감소하였다(p<0.01). 혈장 인슐린 농도(μU/mL)는 당뇨군에서 8.5±0.5로서 대조군의 20.6±1.4보다 유의하게 낮았으며(p<0.001) 운동부하후에는 운동부하전과 비교하여 차이가 없었다. 당뇨군에서 실제운동부하의 정도를 평가하기 위해서 측정한 운동부하후 골격근과 간의 당원농도(mg/100 g wet wt.)는 각각 1.0±0.1과 7.7±0.8로서 운동부하전과 비교시 모두 유의하게 감소하였다(p<0.001, p<0.01). 당뇨군의 골격근과 간의 항산화효소 즉 superoxide dismutase(SOD), glutathione peroxidase(GPX) 및 catalase(CAT)의 활성도는 운동부하에 의해서 각기 다른 반응을 보였다. 골격근의 SOD 활성도(unit/mg protein)는 대조군에서 6.3±0.2였으며 당뇨군에서는 5.8±0.2로서 대조군과의 사이에 유의한 차이를 발견할 수 없었으나 운동부하후에는 5.0±0.1로서 대조군과 운동부하전 당뇨군보다 유의하게 감소하였다(p<0.001, p<0.01). GPX 활성도(nmol/min/mg protein)는 당뇨군에서 운동부하전후에 각각 2.3±0.2와 1.8±0.1로서 대조군의 1.6±0.0보다 다같이 높았으나(p<0.05, p<0.05) 운동부하에 의해서 영향을 받지 않았다. CAT 활성도(μmol/min/mg protein)는 당뇨군에서 7.6±0.7로서 대조군의 6.3±0.7과 비교하여 차이가 없었으나 운동부하후에는 4.6±0.3으로서 대조군보다 감소하였으며(p<0.05) 당뇨군의 운동부하전보다도 감소하였다(p<0.01). 당뇨군의 MDA 농도는 대조군과 비교하여 차이가 없었으며 당뇨군에서 운동부하에 의한 영향도 받지 않았다. 간의 SOD 활성도는 대조군에서 11.3±0.2였으며 운동부하전 당뇨군에서는 9.6±0.3으로서 유의하게 감소하였다(p<0.01). 당뇨군에서 운동부하전후 측정한 SOD 활성도는 대조군과 비교하여 다같이 감소하였으나(p<0.01, p<0.001), 운동부하에 의한 영향은 없었다. 당뇨군의 GPX와 CAT의 활성도는 대조군과 비교하여 유의한 차이가 없었으며 당뇨군에서 운동 부하에 의한 변화도 없었다. 운동부하전 당뇨군의 MDA 농도(nmol/g wet wt.)는 38.5±1.3으로서 대조군의 24.8±0.9에 비해서 유의하게 증가하였으며(p<0.001) 운동부하에 의해서는 대조군보다는 높았으나(p<0.001) 운동부하전과 비교하여서는 차이가 없었다. 이상의 결과를 종합하면 당뇨쥐에서 골격근은 운동부하로 인한 산화 스트레스에 대한 적응과정을 통해서 손상이 없었으나, 간 조직은 당뇨병 자체로 인한 산소유리기의 발생으로 손상의 위험이 있었으나 운동부하에 의한 더 이상의 손상은 없었다. Background : The purpose of the present study was to investigate the effect of exercise on the activities of antioxidant enzymes, superoxide dismutase(SOD), glutathione peroxidase(GPX) and catalase(CAT) of skeletal muscle(gastrocnemius) and liver in streptozotocin(STZ) induced diabetic rats. The malondialdehyde(MDA) concentration was also measured as an index of lipid peroxidation of the tissues by exercise-induced oxidative stresses in diabetic rats. Material and Methods : Male Sprague-Dawley rats were randomly divided into control and STZ-induced diabetic rats. The STZ in citrate buffer solution was injected twice at 5 days intervals intraperitoneally(50, 70 mg/kg respectively). On the 28th day after the first STZ injection, the diabetic animals were randomly divided into pre- and post-exercise groups. The exercise was introduced to the rats of post-exercise group by treadmill running until exhaution with moderate intensity (V_O2max : 50-70%) of exercise. The duration of average running time was 2 hours and 19 minutes. Results : The blood glucose concentration was increased(p<0.001) and plasma insulin concentration was decreased(p<0.001) in the diabetic rats. The glycogen concentration in the muscle and liver was decreased by exhaustive exercise in the diabetic rats(p<0.001). In the skeletal muscle, the activities of GPX was increased(p<0.05) and the activities of SOD and CAT were not changed in the diabetic rats compare to those of the control rats. The activities of GPX was not changed by exercise but the activities of SOD(p<0.01) and CAT(p<0.01) were decreased by exercise in the diabetic rats. The concentration of MDA was not changed by exercise in diabetic rats, and the values of pre-exercise and post-exercise diabetic rats were not different from the value those of control rats. In the liver, the activities of SOD was decreased(p<0.01), and the activities of GPX and CAT were not changed in diabetic rats compared to the values of control rats. The activities of SOD, GPX and CAT were not changed by exercise in diabetic rats but the activity of SOD seemed to decrease slightly. The MDA concentration was increased in the diabetic rats compared to the values of control rats(p<0.001), but there was no change of MDA concentration by exercise in diabetic rats. Conclusions : In summary, exhaustive physical exercise did not seem to impose oxidative stress on thee skeletal muscle because of due to oxygen free radicals, regardless of the decrease in SOD and CAT in the diabetic rats. In liver tissue, the tissue damage by oxidative stress was observed in diabetic rats but the additional tissue damage by exhaustive physical exercise was not observed.

흰쥐의 샘창자 발생에 대한 Lectin 결합양상

최병태,조운복 대한해부학회 1997 Anatomy & Cell Biology Vol.30 No.5

인슐린 비의존성 당뇨병 동물모델에서 미토콘드리아 DNA 복제수의 감소

송지현,임선희,김영미,한복기,이홍규,박경수,Suzuki, S. 국립보건연구원 1999 국립보건원보 Vol.36 No.-

정상 혈압쥐와 본태성 고혈압쥐 노화 적혈수에서의 Na, K-ATPase에 관한 연구

정성훈,박창길,허강민,석정호,이재흔 충남대학교 의과대학 지역사회의학연구소 1992 충남의대잡지 Vol.19 No.1

To study the change of Na, K-ATPase of aged erythrocytes in the normotensive and hypertensive rats, the young and aged erythrocytes of Sprague-Dawley rats or spontaneously hypertensive rats were fractionized by density gradient, and ouabain sensitive Rb-uptake and [^3H] ouabain binding sites were measured. 1. In the spontaneously hypertensive rats, blood pressure was significantly increased to 151.5/110.0mmHg(systolic/diastolic). Mean corpuscular volume and membrane protein(mg/10^9 RBC) were decreased and hemoglobin content was increased in the aged erythrocytes. 2. In the normotensive rats, ouabain sensitive Rb-uptake of young erythrocyte was increased as increase of Rb concentration from 4 mM to 8 or 16 mM in the reaction medium, but that of aged erythrocyte was lower than that of young erythrocyte. 3. In the spontaneously hypertensive rats, ouabain sensitive Rb-uptake of young erythrocyte was also increased as increase of Rb concentration in the medium, but lower than that of young erythrocyte of normotensive rats, and that of aged erythrocyte was also decreased compared to that of young erythrocyte and that of aged erythrougte of normotensive ratc. 4. [^3H] ouabain binding sites of aged erythrocyte of normotensive rats and young or aged erythrocyte of spontaneously hypertensive rats were lower than that of young erythrocyte of normotensive rats. From the above results, it is suggested that the decreased activity of Na, K-ATPase in the aged erythrocyte of normotensive and spontaneously hypertensive rats may due to the decreased numbers of enzymes, and these enzymes in the erythrocytes of spontaneously hypertensive rats would changed from the younger erythrocytes than those of normotensive rats or one-kidney Goldblatt hypertensive rats.

본태성 고혈압쥐의 성장에 따른 뇌신경 세포막 Na, K-ATPase변동에 관한 연구

류석천,허강민,석정호,이재흔 충남대학교 의과대학 지역사회의학연구소 1992 충남의대잡지 Vol.19 No.1

To investigate the development change of synaptosomal Na, K-ATPase of hypertensive rat, Na, K-ATPase activity and ouabain binding sites were measured in the synaptosomal membrane prepared from 3 days-, 2 weeks-, 20 weeks- old Sprague-Dawley rats and spontaneously hypertensive rats Resulrs are as follows; 1. in the synaptosomal Na, K-ATPase of the normotensive and hypertensive rats, there were 2 kinds of isozymes, high affinity site(IC_(50):80-260 nM) and low affinity site(IC_(50):30-60 μM) 2. Synaptosomal Na, K-ATPase activity was increased in 2 and 20 weeks(high affinity site) or 2 weeks(low affinity site) old compared to that in 3 days old rat, and showed a tendency of decrease in 33 weeks old compared to that in 20 weeks old rats(high affinity site) in both groups. 3. Synaptosomal Na, K-ATPase activities of hypertensive rats were low in 3 days and 2 weeks old(high affinity site) or 3 days old (low affinity site) compared to that age groups of normotensive rats. 4. In the ouabain binding experiments, Kd value(0.1-0.2 μM) for ouabain was slightly increased with increase of age, but no difference between normotensive and hypertensive rats was detected. 5. The numbers of ouabain binding sites were increased in 2 weeks and 20 weeks old compared to those in 3 days old rats, and showed a tendency of decrease in 33 weeks old compared to that in 20 weeks old rats. 6. In the hypertensive rats, the number of ouabain binding sites was low in 3 days, compared to that of the correponding age group of normotensive rats. From the above results, it is suggested that in the spontaneously hypertensive rat, 1) synaptosomal Na, K-ATPase of high affinity site or low affinity site is increased significantly after birth as well as in the normotensive rat, 2) but significantly less than that of normotensive rats in early periods after birth and this may due to the low concentration in both high and low affinity Na, K-ATPase isozymes for ouabain.