| Summary: | 碩士 === 國立臺灣大學 === 藥理學研究所 === 84 === Esculetin 中藥材茵陳的成份之一。我們利用活體動物模式來研究
esculetin在活體動物之作用，進而評估esculetin對抗動脈硬化病變之機
轉。動物分為五組：(1)正常組(2)高膽固醇飼料組(3)高膽固醇糖尿病組
(4)esculetin治療之高膽固醇飼料組(5)esculetin 治療之高膽固醇糖尿
病組。血中膽固醇及三酸甘油酯的測定，esculetin處理高膽固醇糖尿病
組可明顯的降低。光學顯微鏡觀察血管心臟形態變化，esculetin處理的
兔子會減少主動脈所發生的泡沫細胞及平滑肌細胞的增生，可改善心肌細
胞肥厚及冠狀動脈硬化的現象。逆轉錄-聚合酵素連鎖反應方法分析基因
表現。 esculetin處理可降低主動脈弓、胸主動脈PDGF-A mRNA的表現，
及腹主動脈、左心室TGF-beta1 mRNA的表現。esculetin在高血脂兔子的
藥理作用有：(1)降低血中膽固醇、三酸甘油酯濃度。(2)改善主動脈之動
脈硬化病變，心肌肥大及冠狀動脈硬化形態上之病變。(3)降低主動脈弓
、胸主動脈 PDGF-A之基因表現，及降低腹主動脈、 左心室TGF-beta1之
基因表現。血管平滑肌細胞的增生是造成動脈粥狀硬化的主要原因之一。
本研究培養 A7r5 cell為材料，來研究中藥材銀杏之成份myricetin對平
滑肌細胞增生的影響。5%胎牛血清刺激A7r5細胞增生下，myricetin能抑
制細胞增生， 100 micromolar達極大抑制作用72.2±9.0%，IC50為13.5
±7.5 micromolar。CEM cell則在10%胎牛血清下，myricetin也能抑制細
胞增生在100 micromolar達極大抑制作用為52.6 ±18.5%，IC50為25.8
±2.9 micromolar。Myricetin(1-100 micromolar)以劑量相依性抑制A7
r5細胞 protein tyrosine kinase活性(100 micromolar抑制65.5±2.8%)
。對PMA激活之分離的cytosolic protein kinase C，myricetin具有明顯
直接抑制作用(100 micromolar抑制 53.3±7.4%)。以100nM PMA刺激A7r5
細胞，PKC translocation及down-regulation的time courses發現，在
PMA處理10分鐘時，PKC活化達最高值，隨時間延長至25 分鐘時，PKC
down-regulation。 Myricetin(100 micromolar)對PMA處理10分鐘活化之
PKC translocation具有抑制作用25.0±4.8% inhibition (P＜0.01)。
Esculetin is from Artemisia scoparia. The in vivo
pharmacological actions of esculetin were investigated.Five
groups of rabbits : (1)normal(2)cholesterol-fed(CHOL)(3)
cholesterol-fed diabetic (CHOL+DM)(4)esculetin-treated
cholesterol-fed(CHOL+esculetin)(5) esculetin-treated
cholesterol-fed diabetic(CHOL+DM+ esculetin). Esculetin
treatment(5mg/kg/day, i.m.)reduced the plasma total cholesterol
and total triglyceride in CHOL+DM rabbits. Six weeks after
cholesterol feeding,the aorta and left ventricle were dissected.
In the rabbits treated with esculetin,there were fewer
pathological morphological changes found in vascular segments
and left ventricle.The reverse transcription-polymerase chain
reaction analysis of mRNAs levels demonstrated that esculetin
treatment reduced the enhanced expression of PDGF-A mRNA in
aorta arch and thoracic aorta,and TGF-beta1 mRNAs in abdominal
aorta and left ventricle in CHOL+DM rabbit.These results
suggest that esculetin protects against some alterations in the
hyperlipidaemic diabetic rabbit.The effects of myricetin is
from Ginkgo biloba.Myricetin (1-100 micromolar) dose
dependently inhibited the proliferative response in A7r5 cells
(IC50 of 13.5±7.5 micromolar;72.2±9.0% inhibition at 100
micromolar)and CEM cells (IC50 of 25.8±2.9 micromolar
;52.6±18.5% inhibition at 100 micromolar).The protein
tyrosine kinase activity stimulated by 5% FCS in the A7r5
cells was significantly reduced by myricetin treatment(65.5
±2.8%inhibition at 100 micromolar).The isolated cytosolic
protein kinase C activity stimulated by PMA was reduced by
directly incubating with myricetin (100 micromolar)(53.3±7.4%
inhibition).Myricetin (100 micromolar) inhibited the PKC
translocation after PMA treatment, the enhanced membrane PKC
was reduced by 25.0±4.8% (P＜0.01).
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