• Journal of Ginseng Research
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• 제13권2호
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• pp.202-210
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• 1989

인삼 성분이 prostaglandin 등 arachidonic acid 대사산물 생성에 미치는 영향을 실험함으로써 인삼의 약리학적 작용기전을 간접적으로 모색하였다. 즉, [$^3H$]-arachidonic acid를 기질로 넣어주고 토끼 신장 micorsome, 소의 대동맥 microsome, 정상 성인의 혈소판 homogenate 등을 효소원으로 한 in vitro 생합성 과정에 변화를 주는 수종 인삼 saponin 성분의 효과를 검정하였다. 실험에 사용한 인삼 saponin 성분은 panaxadiol, panaxatriol 및 protopanaxadiol계 soponin류인 Ginsenoside $Rb_2$(G-$Rb_2$), Ginsenoside Rc(G-Rc) 및 protopanaxatriol계 saponi류인 Ginsenoside (G-$Rb_2$)이었다. 1. Arachidonic acid로부터 생성된 총 cycoloxygenase 반응생성물 및 malondialdehyde의 양은 실험에 사용한 인삼 saponin 성분의 전 농도 범위에서 유의적인 변화를 보이지 않았는데 이는 인삼 saponin 성분들은 cyclooxygenase에 직접 작용하지 않는다는 것을 설명해 준다. 2. Panaxdiol($500{\mu}g$/ml)은 $PGE_2$ 생성에는 영향이 없으나 $PGF_2$ 및 $TXB_2$의 생성을 감소시켰으며 동시에 6-keto-$PGF_{1{\alpha}}$의 생성은 증가시켰다. Panaxatriol도 유사한 양상을 보였다. 3. G-$Rb_2$, Rc, Re에 의해 $TXB_2$의 생성은 농도 의존적으로 감소하였으나 6-keto-$PGF_{1{\alpha}}$의 생성은 유의적으로 증가하였다. 또한 arachidonic acid와 $TXA_2$ 유사제인 U46619(9,11-methanoepoxy $PGH_2$)로 유도한 혈소판 응집 현상은 세 ginsenoside에 의해 억제되었다. G-Re의 6-keto-$PGF_{1{\alpha}}$생성증가 효과는 prostacyclin 합성효소억제제에 의해 길항하였다. 이상의 결과와 같이 인삼saponin 성분들은 arachidonic acid로부터 cyclooxygenase를 통해 일단 생성된 endoperoxide에서 각각의 prostaglandin을 생성하는 효소, 특히 G-$Rb_2$는 $TXA_2$ synthetase에 강력한 억제제로, G-Re는 prostacyclin 생합성에 촉진데로 심혈관계 균형에 기여하리라 생각된다.

• 한국영양학회:학술대회논문집
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• 한국영양학회 1997년도 추계학술대회 초록
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• pp.42-42
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• 1997

• 대한약리학회지
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• 제20권1호
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• pp.41-46
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• 1984

카드뮴중독으로 혈소판응집이 항진되어 고혈압 또는 동맥경화증이 발생한다는 연구보고를 감안하여 가토와 흰쥐의 생체내 실험으로서 미세혈전의 형성, Malondialdehyde(MDA) 및 thromboxane $B_2(TXB_2)$치에 미치는 카드뮴의 효과를 검토하고, in vitro실험으로 카드뮴을 처치한 가토 대동맥절편이 혈소판응집에 미치는 영향을 관찰하였으며, prostacyclin의 합성능력을 측정하여 그 결과를 다음과 같이 요약하였다. 1)Cadmium chloride 2mg/kg을 매주 동물의 복강내에 주입하였을 때 미세혈전형성이 증가되었다. 2) 카드뮴 중독동물의 platelet-rich plasma (PRP)는 MDA와 $TXB_2$형성이 정상동물에서 보다 현저히 증가되었다. 3) 카드뮴을 중독시킨 가토의 platelet-poor plasma (PPP)에서의 lipid peroxide치는 대조군과 차이가 없었다. 4) In vitro 실험으로, 가토대동맥 절편에서의 6-keto-$PGF_{1{\alpha}}$의 생성은 카드뮴 농도에 비례하여 억제되었고 이때 혈소판 응집률의 증가와 평행하였다. 5) 이상의 결과로서 카드뮴은 동맥내피세포에서 prostacyclin 합성을 억제할 뿐만 아니라 혈소판에서 $TXA_2$합성을 촉진시켜 그 결과로 혈소판 응집률을 증가시켰음을 알 수 있었다.

• Journal of Chest Surgery
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• 제20권4호
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• pp.643-654
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• 1987

The effect of prostacyclin[PGI, ] on myocardial preservation during global ischemia was studied in the isolating working rabbit heart model. Forty hearts underwent a 15 minute period of retrograde nonworking perfusion with Krebs-Henseleit buffer solution [37*C] and were switched over to the working mode for 15 minutes. After baseline measurement of heart rate, peak aortic pressure, aortic flow, and coronary flow, all hearts were subjected to 60 minutes of ischemic arrest at 10*C induced with St. Thomas Hospital cardioplegic solution: Group I had single dose cardioplegia, Croup II double dose, Croup III oxygenated double dose, and Group IV single dose with PCI, infusion [10ng/min./gm heart weight]. Hearts were then revived with 15 minute period of nonworking reperfusion at normothermia, followed by 30 minutes of working perfusion. Repeat measurements of cardiac function were obtained and expressed as a percent of the preischemic baseline values. Oxygen content of arterial perfusate and coronary effluent was measured by designed time interval. Leakage of creatine kinase was determined during post-ischemic reperfusion period. Finally wet hearts were weighed and placed in 120*C oven for 36 hours for measurement of dry weight. In the PGI, treated group [IV], heart rate increased consistently throughout the period of reperfusion from 100*5.0% [p<0.001] to 107*6.2% [p<0.001]. The percent recovery of aortic flow showed 95*5.7% [p<0.001] at the first 3 minute and full recovery through the subsequent time. Coronary flow was augmented significantly in the 3 minute [96*6.2%, p<0.001] and then sustained above baseline values. Among the Croup I, II, and III, all hemodynamic values were significantly below preischemic levels. PGI2 relatively increased oxygen delivery [1.22*0.19ml/min, p<0.001] and myocardial oxygen consumption [0.90*0.13ml/min, p<0.001] during reperfusion period. Leakage of creatine kinase in the PGI2 group was 9.3*1.58IU/15min [p<0.001]. This was significantly lower than Group I [33.0*2.68 IU/15min]. The water content of PCI2 treated hearts [81*0.9%, p<0.001] was also lower than the other groups.

• 한국식품영양과학회지
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• 제27권1호
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• pp.175-181
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• 1998

The relation between lipid peroxidation and thrombotic reaction were investigated in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 100$\pm$10gm were randomly assigned to normal and STZ-induced diabetic group(DM). Diabetes was experimentally induced by intravenous injection of 55mg/kg of body weight of STZ in citrate buffer(pH 4.3) after 4 weeks feeding of basal diet. Animals were sacrificed at the 6th day of diabetic states. Body weight gains were lower in diabetic group after STZ injection. Serum levels of thiobarbituric acid reacting substances(TBARS) that were markedly increased in DM group compared with of normal group. TBARS levels of HDL and LDL were similar patterns to total TBARA of serum. Activities of platelet phospholipase A2(PLA2) were higher in diabetic group than those of normal group. Activities of platelet cyclooxygenase were 106% in DM group than normal group. Platelet thromboxane A2(TXA2) formation was increased in DM group than normal group. Production of aortic prostacyclin(PGI2) was lower in diabetic group than that of normal group. PGI2/TXA2 ratios were decreased by 55% in DM groups than those of normal group. The present results indicate that STZ-induced diabetic rats are more sensitive to oxidative stess which leads to acceleration of lipid peroxidation and platelet aggregability. In conclusion, accelerating effect of lipid peroxidation and thrombogenesis in diabetic state is regareded to be resulted from enhancement of PLA2 activity and arachidonic acid metabolism, inhibition of antiaggrgating agent and aortic PGI2 formation.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.331-343
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• 1998

Sublethal dose of bacterial lipopolysaccharide (LPS) would induce protection against cardiac ischemic/reperfusion (I/R) injury. This study examines the following areas: 1) the temporal induction of the cardio-protection produced by LPS; and 2) the relations between a degree of protection and the myocardial prostacyclin ($PGI_2$) production. Rats were administered LPS (2 mg/kg, i.v.), and hearts were removed 1, 4, 8, 14, 24, 48, 72,and 96 h later. Using Langendorff apparatus, haemodynamic differences during 25 min of global ischemia/30 min reperfusion were investigated. The concentration of $PGI_2$ in aliquots of the coronary effluent was determined by radioimmunoassay as its stable hydrolysis product $6-keto-PGF1_{\alpha}$ and lactate dehydrogenase release were measured as an indicative of cellular injury. LPS-induced cardiac protection against I/R injury appeared 4 h after LPS treatment and remained until 96 h after treatment. $PGI_2$ release increased 2-3 fold at the beginning of reperfusion compared to basal level except in hearts treated with LPS for 48 and 72 h. In hearts removed 48 and 72 h after LPS treatment, basal $PGI_2$ was increased. To determine the enzymatic step in relation to LPS-induced basal $PGI_2$ production, we examined prostaglandin H synthase (PGHS) protein expression, a rate limiting enzyme of prostaglandin production, by using Western blot analysis. LPS increased PGHS protein expression in hearts at 24, 48, 72, 96 h after LPS treatment. Induction of PGHS expression appeared in both isotypes of PGHS, a constitutive PGHS-1 and an inducible PGHS-2. To identify the correlationship between $PGI_2$ production and the cardioprotective effect against I/R injury, indomethacin was administered in vivo or in vitro. Indomethacin did not inhibit LPS-induced cardioprotection, which was not affected by the duration of LPS treatment. Taken together, our results suggest that $PGI_2$ might not be the major endogenous mediator of LPS-induced cardioprotection.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.435-441
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• 1998

We examined effects of interleukin $1{\alpha}$ ($IL1{\alpha}$) and phorbol 12, 13 dibutyrate (PDB), an activator of protein kinase C, on mRNA for Prostaglandin H synthase (PGHS) and prostanoid production in cultured ovine meningeal fibroblasts. Immuno- and morphologically-identified fibroblasts were derived from cerebral cortex and white matter from fetal lambs (approximately 120 days gestation) and grown to confluence on glass coverslips in 12 well plates. Levels of prostaglandin $F_{2{\alpha}}$ and the stable hydrolysis product of prostacyclin (i.e., $6-keto-PGF_{1{\alpha}}$) were determined using enzyme immunoassay. Relative amounts of mRNA were determined by in situ hybridization using ovine cDNA for PGHS1. $IL1{\alpha}$ (10 ng/ml) increased mRNA levels over baseline by $62{\pm}19%$ (p＜0.05) at 60 min., $37{\pm}12%$ (NS) at 120 min., and $36{\pm}18%$ (NS) at 240 min (n=12). Levels of $6-keto-PGF_{1{\alpha}}$ were $148{\pm}18%$ pg/ml during baseline, $246{\pm}41%$ pg/ml at 60 min., $248{\pm}40%$ pg/ml at 120 min., and $259{\pm}62%$ pg/ml at 240 min (all p＜0.05) (n=12). $PGF_{2{\alpha}}$ was increased although it wasn't statistically significant. However, $IL1{\alpha}$ decreased $PGE_2$ level significantly (all p＜0.05). PDB $(10^{-6}M)$ increased mRNA levels over baseline by $25{\pm}6%$ after 30 min., $40{\pm}6%$ after 60 min., and $20{\pm}8%$ after 90 min. (n=9) (all p＜0.05). Levels of $6-keto-PGF_{1{\alpha}}$ were $200{\pm}43%$ pg/ml during baseline, $202{\pm}43%$ pg/ml after 30 min. (NS), $268{\pm}58%$ pg/ml after 60 min. (p＜0.05), and $296{\pm}60%$ pg/ml after 90 min. (p＜0.05) (n=9). Levels of $PGF_{2{\alpha}}$ were $178{\pm}26%$ pg/ml during baseline, $300{\pm}30%$ pg/ml after 30 min., $299{\pm}35%$ pg/ml after 60 min., and $355{\pm}32%$ pg/ml after 90 min (all p＜0.05) (n=6). Actinomycin-D (1 mg/ml) prevented increases in mRNA, $6-keto-PGF_{1{\alpha}}$, and $PGF_{2{\alpha}}$ at 60 min. for both $IL1{\alpha}$ and PDB. We conclude that cerebral fibroblasts are avid producers of prostanoids, and that enhanced production of PGHS is responsible for augmented $PGF_{2{\alpha}}$ and prostacyclin production in the presence of an activator of protein kinase C and for decreased $PGE_2$ and increased prostacyclin production in the presence of $IL1{\alpha}$.

• Nutritional Sciences
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• 제5권4호
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• pp.184-189
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• 2002

The effects of dietary Int levels on lipid metabolism under fixed P/S (1.3) and n-6/n-3 (5.1) fatty acid ratios were examined in rats using palm oil, soybean oil and perilla oil. These ratios correspond to the recommended composition of dietary fat for humans. The range of dietary fat levels was 5-20% by weight (11.8-39.3% of total energy). The levels of dietary fat did not influence the concentrations of serum and liver cholesterol, whereas the level of triglycerides was gradually elevated with increasing levels of dietary fat, especially in the liver. The fatty acid composition of tissue phosphatidylcholine seemed to vary with the different levels of fat. The ratio of linoleic acid to arachidonic acid was increased more significantly in the heart than in the liver. In adipose tissue total lipids, the percentages of saturated and monounsaturated fatty acids decreased, whereas the percentage of polyunsaturated fatty acid increased, with increasing dietary Int levels. In addition, though the level of aortic prostacyclin was not uniformly affected by increasing dietary fat levels, thromboxane A2 production by platelets tended to increase with higher levels of dietary fat, suggesting an increased risk of thrombosis in this situation. Thus, even though dietary fat may have desirable compositions of fatty acids, these excessive consumption can produce unfavorable metabolic responses.

• Biomolecules & Therapeutics
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• 제3권2호
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• pp.104-110
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• 1995

Arachidonic acid (AA, C20 : 4, $\omega$-6) and eicosapentanoic acid (EPA,C20 : 5, $\omega$-3), which are polyunsaturated fatty acids forming eicosanoids, were tested for their effects on blood pressure in Wistar rats and SHR. AA is the most important precursor for the biosynthesis of eicosanoids which include the prostaglandins, prostacyclin (PGI$_2$), thromboxane $A_2$ (TXA$_2$) and the leukotriens. TXA$_2$is a potent vasoconstrictor and a powerful inducer of platelet aggregation causing myocardial infarction and hypertention. In contrast, PGI$_2$ induces vasodilation and inhibits platelet aggregation. In this study, AA markedly increased blood pressure, but its effect was antagonized by both EPA, a structural analog of AA, and dazmegrel, a TX synthetase inhibitor. Also, AA enhanced the antihypertensive effects of hydralazine and captopril, and EPA reduced TXA$_2$ production. These results indicate that the hypotensive effects of EPA might be closely related to the decrease in TXA$_2$ biosynthesis due to competitive inhibition by structural similarity of the EPA to the AA, the precursor of TXA$_2$.

• 대한수의학회지
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• 제33권3호
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• pp.443-454
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• 1993

Shiga-like toxin-II(SLT-II)-producing Escherichia coli 0157 : H7 strain B2387이 분비하는 SLT-II가 gnotobiotic자돈에서의 뇌혈관 병변을 일으키는 pathogenesis에 관해서 실험을 했다. 제왕절개 수술로 태어난 자돈들을 두 그룹으로 나누어서, 한 그룹에는 SLT-II 중화항체를 포함한 혈청을 구강을 통해서 수동면역을 시키고, 또다른 한 그룹에는 SLT-II 중화항체가 포함되어 있지 않은 혈청을 구강을 통해서 수동면역시켰다. 24시간후 두 그룹 모두에게 SLT-II producing Escherichia coli O157 : H7 strain B2387를 구강으로 접종했다. SLT-II 중화항체가 포함되어 있지 않은 혈청으로 수동면역시킨 그룹의 자돈들은 설사와 맹결장염, 신경증상, 뇌혈관병변을 일으키고, plasma의 prostacyclin의 level이 증가했다. 하지만 SLT-II 중화항체가 포함되어 있는 혈청으로 수동면역시킨 그룹의 자돈들은 설사와 맹결장염은 유발했지만, 신경증상과 뇌혈관병변은 관찰되지 않았고, prostacyclin의 level도 증가하지 않았다. 이런 실험결과는 SLT-II 중화항체는 뇌혈관병변은 방어하지만 맹결장염은 방어하지 못한다는 의미를 나타내며, prostacylin의 증가는 뇌혈관의 endothelium의 병변을 의미한다.