• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.263-273
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• 1999

The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

• 한국발생생물학회지:발생과생식
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• 제28권1호
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• pp.21-28
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• 2024

Present study aimed to investigate the temporal changes in expression of some reproductive hormones in testis, originally found in hypothalamus and pituitary. Rats were sacrificed on postnatal day 23 (PND23; immature), pubertal (PND53) and PND 81 (young adult). The testicular RNAs were extracted, and semi-quantitative PCRs for gonadotropin-releasing hormone (GnRH), kisspeptin 1 (KiSS1), pituitary adenylate cyclase-activating polypeptide (PACAP), LH subunits and LH receptor were performed. Transcript levels of GnRH and KiSS1 at PND23 were significantly higher than levels of PND53 and PND81 (p<0.001). PACAP mRNA level at PND23 was significantly lower than those of PND53 and PND81 (p<0.001). The mRNA levels of both testis type and pituitary type luteinizing hormone β subunit (tLHβ and pLHβ, respectively) at PND23 were significantly lower than levels of PND53 and PND81 (p<0.001). The mRNA level of glycoprotein hormone common alpha subunit (Cgα) at PND23 was significantly lower than those of PND53 and PND81 (p<0.001). Present study revealed the intratesticular expression of KiSS1 and GnRH showed a very similar trend while the expression of PACAP in the testis showed reversed pattern. The expressions of LHβ subunits (tLHβ and pLHβ) were very low during immature stage then increased significantly during puberty and early adulthood. Our attempt to study the local role(s) of intratesticular factors will be helpful to achieve precise understanding on the testis physiology and pathology.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.603-611
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• 1997

The motor evoked potentials (MEPs) have been advocated as a method of monitoring the integrity of spinal efferent pathways in various injury models of the central nervous system. However, there were many disputes about origin sites of MEPs generated by transcranial electrical stimulation. The purpose of present study was to investigate the effect of major extrapyramidal motor nuclei such as lateral vestibular nucleus (VN) and medullary reticular nucleus (mRTN) on any components of the MEPs in adult Sprague-Dalwey rats. MEPs were evoked by electrical stimulation of the right sensorimotor cortex through a stainless steel screw with 0.5mm in diameter, and recorded epidurally at T9 - T10 spinal cord levels by using a pair of teflon-coated stainless steel wire electrodes with 1mm exposed tip. In order to inject lidocaine and make a lesion, insulated long dental needle with noninsulated tips were placed stareotoxically in VN and mRTN. Lidocaine of $2{\sim}3\;{\mu}l$ was injected into either VN or mRTN. The normal MEPs were composed of typical four reproducible waves; P1, P2, P3, P4. The first wave (P1) was shown at a mean latency of 1.2 ms, corresponding to a conduction velocity of 67.5 m/sec. The latencies of MEPs were shortened and the amplitudes were increased as stimulus intensity was increased. The amplitudes of P1 and P2 were more decreased among 4 waves of MEPs after lidocaine microinjection into mRTN. Especially, the amplitude of P1 was decreased by 50% after lidocaine microinjection into bilateral mRTN. On the other hand, lidocaine microinjection into VN reduced the amplitudes of P3 and P4 than other MEP waves. However, the latencies of MEPs were not changed by lidocaine microinjection into either VN or mRTN. These results suggest that the vestibular and reticular nuclei contribute to partially different role in generation of MEPs elicited by transcranial electrical stimulation.

• Clinical and Experimental Pediatrics
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• 제51권10호
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• pp.1102-1111
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• 2008

목 적: Resveratrol은 주로 포도나무의 과실이나 잎 부위에서 추출되는 성분으로, 주로 심질환에서 암 예방 효과, 항염증 효과, 항산화 효과의 기능이 밝혀지고 있다. 최근 성인에 대한 신경보호 효과가 있는 것으로 알려졌지만. 신생아에서 연구는 아직까지 없다. 그래서 본 연구에서는 resveratrol이 신생 백서의 저 산소 허혈 뇌손상에서 신경보호 효과가 있는지를 알아보고자 실험하였다. 방 법: 재태기간 18일된 태아 백서의 대뇌피질 세포를 배양하여 1% $O_2$ 배양기에서 저 산소 상태로 뇌세포손상을 유도하여 저 산소군, 저 산소 30분 전 resveratrol 투여군 (1, 10, $30{\mu}g/mL$)으로 나누어 정상 산소군과 비교하였다. 또한, 동물 모델에서는 생후 7일된 백서의 좌측 총 경동맥을 결찰한 후 저 산소 (8% $O_2$) 상태로 2.5시간 노출시켜서 저 산소 허혈 뇌 손상을 유발하였고, 뇌손상 전후 30분에 resveratrol을 체중 kg당 30 mg을 복막내로 투여하였다. 세포사멸사의 관련을 알아보기 위해 Bcl-2, Bax, caspase-3 primer를 이용한 실시간 중합효소연쇄반응과 동일 항체를 이용한 Western blotting을 시행하였다. 결 과: 태아 백서 뇌세포 배양 실험에서 저 산소군의 경우 Bcl-2의 발현이 정상 산소군에 비해 감소하였고, Bax의 발현과 caspase-3의 발현, 그리고 Bax/Bcl-2의 비율은 증가하였다. Reaveratrol을 투여한 실험군의 경우에서는 Bcl-2 발현은 증가하였고, Bax의 발현과 caspase-3의 발현, Bax/Bcl-2의 비율은 저 산소군에 비하여 감소하는 결과를 보였다. 또한 이는 저 산소 허혈 뇌손상 동물 모델에서도 같은 결과를 보였다. 결론: 본 연구에서 resveratrol은 주산기 저 산소 허혈 뇌손상에서 세포사멸사 작용의 억제를 통하여 신경보호 역할을 하는 것을 알 수 있었다.

• Clinical and Experimental Reproductive Medicine
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• 제21권1호
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• pp.121-130
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• 1994

Expression of gonadotropin releasing hormone(GnRH) has been described in the rat ovary. It remains, however, unkown whether GnRH is synthesized as a prohormone. Therefore, this study was performed to verify the expression of pro-GnRH by in situ hybridization and further to investigate the effect of gonadotropin on GnRH or GnRH mRNA in rat ovary by immunohistochemical and in situ hybridization techniques. Adult female Sprague-Dawely rats were used and the estrous cycle was synchronized by intraperitoneal injection of pregnant mare's serum gonadotropin(PMSG). Ovaries were fixed with 4% paraformaldehyde and embedded with G.C.T. compound and cut by cryostat. For immunohistochemistry, avidin-biotin peroxidase complex(ABS) method was employed and for in situ hybridization, $^{35}S$-end labeled oligonucleotide was used and followed by autoradiography. By in situ hybridization using GnRH oligomer and GAP(GnRH associated protein) oligomer, GnRH mRNA and GAP mRNA were co-localized in the fullicular cells, luteal cells, interstitial cells and theca cells. GnRH or GnRH mRNA signals in the ovary increased by human chorionic gonadotropin(hCG) injection. At the 3 and 6 hrs after hCG injection, the number of GnRH and GnRH mRNA containing cells increased rapidly and the density of GnRH and GnRH mRHA culminated at 9 hrs after heG injection. With the follicular development, the high expression of GnRH and GnRH mRNA was also observed within the follicles. After ovulation, the density of GnRH or GnRH mRNA decreased in the follicles but increased in the corpus lutea.

• 한국식품영양과학회지
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• 제37권3호
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• pp.309-316
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• 2008

본 연구에서는 알코올을 이용하여 만성위궤양 실험동물 모델을 확립하고 설정된 동물모델을 대상으로 비타민 E 투여 수준(결핍 0 mg/mL oil/day, 정상 1 mg/mL oil/day, 보충 10 mg/mL oil/day)에 따른 위궤양 치유효과를 살펴보고자 수행되었다. 비타민 E를 투여시킨 기간은 총 7일로서 위의 조직학적 검사, 혈청의 gastrin 농도, 위 조직의 histamine 농도, 위 조직 내의 항산화 효소인 GPx 활성도와 catalase 농도 및 MPO 활성도를 측정하였으며 그 결과를 요약하면 다음과 같다. 만성군에서 식이섭취량과 15% 에탄올 식수섭취량에는 유의적인 차이가 없었으나 체중증가량은 비타민 E 결핍군에서 유의적으로 낮았다. 급성군에 비해 만성군에서 위 무게가 유의적으로 낮게 나타났다. 또한 급성군에서 다량의 출혈과 선상의 괴사가 나타났으며 비타민 E 결핍군 또한 약간의 출혈과 선상의 궤양이 남아있었으나 비타민 E 정상군과 보충군의 경우 출혈이나 궤양은 관찰되지 않았다. 혈청 gastrin의 경우 비타민 E 결핍군에서 유의적으로 높았으며 비타민 E 투여수준에 따라 유의적으로 낮아졌다. 또한 위 조직에서 histamine 농도는 급성군보다 만성군에서 유의적으로 높게 나타났지만 만성군에서 비타민 E의 투여수준에 따른 histamine 농도의 차이는 나타나지 않았다. 위 조직에서의 MDA 농도는 비타민 E 결핍군과 정상군에 비해 보충군에서 유의적으로 높게 나타났으며 급성과 만성유도에 따른 MDA 농도 차이는 관찰되지 않았다. 또한 대표적인 항산화 효소인 GPx와 catalase의 경우 비타민 E 정상군과 보충군에서 유의적으로 낮게 나타났다. 위 조직에서의 MPO 활성도는 비타민 E 결핍군에 비해 정상군과 보충군에서 유의적으로 낮게 나타났다. 결론적으로 알코올로 유도한 만성위궤양 실험동물 모델에서 비타민 E의 보충은 위궤양 치유효과가 있는 것으로 평가되었다. 비타민 E 보충은 혈청 gastrin 농도를 감소시켜 위에서의 산 분비를 감소시키며 또한 위 조직 내의 MPO 활성도를 감소시켜 proinflammatory cytokine을 방출을 억제시키고 결과적으로 위 세포내로의 호중구 침투를 감소시켜 위궤양 치유과정을 촉진시키는 것으로 보인다. 따라서 비타민 E의 결핍상태보다 비타민 E를 보충하였을 때 빠른 위궤양 치유효과가 있는 것으로 사료되며, 평소 권장량을 충족시킬 수 있는 비타민 E의 충분한 식이섭취가 중요하다고 생각한다.

• 대한의생명과학회지
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• 제2권1호
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• pp.71-90
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• 1996

장기간 반복 주행운동이 횐 쥐의 심근에 미치는 효과를 규명하기 위하여 생후 3개월,10개 월 및 20개월 된 횐 쥐를 운동군과 대조군으로 대별하여 motor driven treadmill을 이용하여 Park등이 사용한 방법에 준해서 5개월간, 주 5일 20분간 운동을 시킨 후 심근의 조직 및 세포학적 변화를 관찰하고 심근 세포 내 미세구조 변화를 입체해석학적으로 비교 분석하였다. 연령 증가에 따라 장기간 반복운동이 휜쥐 심근미세구조에 미치는 영향은 8, 15개월의 운동군과 대조군 사이에 뚜렷한 차이를 인정할 수 없으며, 15개월의 운동군에서 대조군에 비하여 변성된 사립체, 리소조옴, 지방적, 공포, 노화색소 등이 증가하는 경향이 있었다. 25개월 운동군은 같은 연령 대조군에 비하여 근원섬유 수축대, 근원섬유 소실, 윤반분리,세포간질 증식, 핵의 변성,교원섬유 근섬유내 침입 등 매우 심한 변화를 보였다. 조직상에 나타나는 early lipofusin과 미세구조상에 나타나는 노화색소는 8, 15개월의 운동군과 대조군 사이에 유의한 차이는 없었으며, 25개월 운동군은 같은 연령 대조군에 비하여 유의한 차이로 증가하였다. Glucose-6-phosphatase 활성도 8, 15개월군에서 운동군과 대조군에서 모두 활성이 높았으며 25개월의 대조군과 운동군에서는 모두 활성이 거의 나타나지 않았다. 미세구조 변화를 입체해석학적으로 분석한 결과 8, 15개월의 대조군과 운동군에서 체적 밀도의 모든 항은 양군사이에 유의한 차이가 없었다. 25개월에서는 세포간질이 대조군에 비하여 운동군이 유의한 증가를 나타내었고, 근원섬유는 유의한 차이는 없지만 증가하는 경향을 보였으며, 사립체는 대조군에 비하여 유의 한 감소를 나타내었고 근형질세망의 체적밀도는 감소하는 경향을 보였다. 사립체와 근원섬유 비는 8개월 운동군에서 유의한 차이는 없지만 대조군에 비하여 높게 나타났으며, 15개월의 운동군과 대조군 사이에서는 차이를 인정할 수 없었다. 그러나 25개월 운동군은 대조군에 비하여 유의한 차이로 감소하였다. 연령증가에 따른 사립체 내막 표면밀도와 사립체수는 대조군과 운동군 사이에는 유의한 변화는 없었다. 본 연구의 성적을 검토한 결과 젊은층(3개월군)과 중령층(10개월군)의 횐 쥐에서는 반복된 지구력운동이 심장에 미치는 역효과를 인정할 수 없었으며 젊은 층의 횐 쥐에서는 오히려 심장기능 강화를 보이는 경향이 나타났으며, 노화층(20개월군)에서 운동군에서는 스트레스로 작용하여 심장기능의 저하를 초래하였다고 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.617-628
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• 1998

In order to understand the pathogenetic mechanism of adult respiratory distress syndrome (ARDS), the role of phospholipase A2 (PLA2) in association with oxidative stress was investigated in rats. $Interleukin-1{\alpha}\;(IL-1,\;50\;{\mu}g/rat)$ was used to induce acute lung injury by neutrophilic respiratory burst. Five hours after IL-1 insufflation into trachea, microvascular integrity was disrupted, and protein leakage into the alveolar lumen was followed. An infiltration of neutrophils was clearly observed after IL-1 treatment. It was the origin of the generation of oxygen radicals causing oxidative stress in the lung. IL-1 increased tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC) in the bronchoalveolar lavage fluid, but mepacrine, a PLA2 inhibitor, did not change the levels of these cytokines. Although IL-1 increased PLA2 activity time-dependently, mepacrine inhibited the activity almost completely. Activation of PLA2 elevated leukotriene C4 and B4 (LTC4 and LTB4), and 6-keto-prostaglandin $F2{\alpha}\;(6-keto-PGF2{\alpha})$ was consumed completely by respiratory burst induced by IL-1. Mepacrine did not alter these changes in the contents of lipid mediators. To estimate the functional changes of alveolar barrier during the oxidative stress, quantitative changes of pulmonary surfactant, activity of gamma glutamyltransferase (GGT), and ultrastructural changes were examined. IL-1 increased the level of phospholipid in the bronchoalveolar lavage (BAL) fluid, which seemed to be caused by abnormal, pathological release of lamellar bodies into the alveolar lumen. Mepacrine recovered the amount of surfactant up to control level. IL-1 decreased GGT activity, while mepacrine restored it. In ultrastructural study, when treated with IL-1, marked necroses of endothelial cells and type II pneumocytes were observed, while mepacrine inhibited these pathological changes. In histochemical electron microscopy, increased generation of oxidants was identified around neutrophils and in the cytoplasm of type II pneumocytes. Mepacrine reduced the generation of oxidants in the tissue produced by neutrophilic respiratory burst. In immunoelectron microscopic study, PLA2 was identified in the cytoplasm of the type II pneumocytes after IL-1 treatment, but mepacrine diminished PLA2 particles in the cytoplasm of the type II pneumocyte. Based on these experimental results, it is suggested that PLA2 plays a pivotal role in inducing acute lung injury mediated by IL-1 through the oxidative stress by neutrophils. By causing endothelial damage, functional changes of pulmonary surfactant and alveolar type I pneumocyte, oxidative stress disrupts microvascular integrity and alveolar barrier.

• 대한소아치과학회지
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• 제25권4호
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• pp.788-796
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• 1998

The purpose of this study was to investigate the effect of various electroacupuncture duration induced by acupuncture point-Zusanli ($S_{36}$) electrical stimulation on inhibition of amplitude of digastric electromyogram (dEMG) evoked by noxious electrical stimuli around the mental foramen. intraperitoneal sodium pentobarbital in an initial dose of 50mg/kg and maintenance doses of 4.5mg/kg/h were given through a cannula in the femoral vein using a constant infusion pump. A pair of stimulating electrodes were inserted for noxious stimuli around the mental foramen. An irritant electronic stimuli pulse (0.2 Hz, 0.1 ms duration) was produced with an intensity of about $1.5{\times}2$ times threshold for evoking the dEMG. The anterior belly of the digastric muscle was exposed and a pair of 0.1mm wire electrodes were inserted for dEMG recording. Acupuncture point stimulation on Zusanli (2 Hz, 250 ${\mu}s$, biphasic pulse, 2 V) was delivered by Dental Electronic Anesthesia (3M, U.S.A). For periods of electronic stimulation of 10, 20, and 30min, the amplitudes of dEMG were measured on the oscilloscope and on the monitor connected to the amplifier. The following results were obtained: The dEMG was decreased to 73.4% of that in the control set after 10 min electroacupunture stimulation (Group I); The dEMG was decreased to 77.1% (10min), 54.0.% (20min) of that in the control set after 20minutes of electroacupunture stimulation (Group II). The dEMG was decreased to 73.3% (10min), 61.9% (20min), 76.2% (30min) of that in the control set after 30 min of electroacupunture stimulation (Group III). From these results, it may be that in the electroacupuncture stimulation on the Zusnali resulted in a reduction of amplitude of dEMG and that the most effective electroacupuncture stimulation period was 20min.

• 생물정신의학
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• 제16권1호
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• pp.5-14
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• 2009

Objectives : Most of the mechanisms reported for antidepressant drugs are the enhancement of neurite outgrowth and neuronal survival in the rat hippocampus. Neural cell adhesion molecule 140(NCAM140) has been implicated as having a role in cell-cell adhesion, neurite outgrowth, and synaptic plasticity. In this report, we have performed to elucidate a correlation among chronic antidepressant treatments, NCAM140 expression, and activation of phosphorylated cyclicAMP responsive element binding protein(pCREB) which is a downstream molecule of NCAM140-mediated intracellular signaling pathway in the rat hippocampus. Methods : Fluoxetine(10mg/kg) was injected acutely(daily injection for 5days) or chronically(daily injection for 14days) in adult rats. RNA and protein were extracted from the rat hippocampus, respectively. Real-time RT-PCR was performed to analyze the expression pattern of NCAM140 gene and western blot analyses for the activation of the phosphorylation ratio of CREB. Results : Chronic fluoxetine treatments increased NCAM140 expression 1.3 times higher than control in rat hippocampus. pCREB immunoreactivity in the rat hippocampus with chronic fluoxetine treatment was increased 4.0 times higher than that of control. Conclusion : Chronic fluoxetine treatment increased NCAM140 expression and pCREB activity in the rat hippocampus. Our data suggest that NCAM140 and pCREB may play a role in the clinical efficacy of antidepressants promoting the neurite outgrowth and neuronal survival.