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研究生:鄭喻仁
研究生(外文):Cheng, Yuh-Ren
論文名稱:粉防己鹼慢性治療對門脈高壓大白鼠的效應
論文名稱(外文):Hemodynamic effects of chronic tetrandrine administration on portal hypertensive rats
指導教授:黃怡超黃怡超引用關係林漢傑林漢傑引用關係
指導教授(外文):Huang, Yi-TsauLin, Han-Chieh
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:傳統醫藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:1997
畢業學年度:85
語文別:中文
論文頁數:105
中文關鍵詞:傳統醫學中國醫學中藥粉防己鹼門脈高壓
外文關鍵詞:TRADITIONAL-MEDICINECHINESE-MEDICINEHERB-MEDICINE
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  • 收藏至我的研究室書目清單書目收藏:1
慢性肝臟疾病佔台灣十大死因之第六位,其所伴隨門脈高壓進而衍生之胃、食道靜脈瘤破裂出血,更高達40%之致死率,因此如何有效降低門脈壓力並預防及治療食道靜脈瘤出血便成為當今重要的研究主題之一。
雖然目前中西醫藥皆有許多治療門脈高壓的方法,但其大多有使用上限制、明顯的副作用、部分作用機轉亦不清楚,且都未能完全矯正門脈高壓的高血流動力學狀態,本論文之研究主要是藉由評估中藥純化物及幾種不同的合併療法,嘗試找尋更適合的門脈高壓治療方式。
粉防己鹼是由中藥防己所純化出來的一個有效成分,慢性給予粉防己鹼,能有效降低PVL組大白鼠門脈壓力,並降低其臟俯血液灌流量、增加臟俯血管阻力、矯正PvL大自鼠部分高血流動力狀態,但此一投予無論對Sham組或PVL組大白鼠皆有降低平均動脈壓、增加心輸出指數之效應。
單獨慢性給予粉防己鹼對PVL大白鼠全身臟俯血液動力學參數有矯正之效果,但在周邊血液動力學參數部分我們也看到某些不利於門脈高壓治療的副作用,因此嘗試以慢性給予粉防己鹼合併octreotide來治療,結果發現單獨慢性給予octreotide能有效的矯正門脈高壓的高血流動力狀態,但並不能使PVL大白鼠恢復至與Sham組大白鼠相同,而慢性給予粉防己鹼合併octreotide治療時,加強了粉防己鹼對PVL大白鼠全身臟俯高血流動力狀態的矯正作用,並且使得粉防己鹼在周邊血液動力學參數部分的副作用消失,轉變為對門脈高壓周邊血液動力學有幫助的效果,但慢性給予粉防己鹼合併octreotide似乎並未提供比單獨慢性給予octreotide更大的治療效應。
在慢性給予propranolol合併octreotide治療方面,單獨慢性給予octreotide或propranolol能有效的降低門脈壓並矯正門脈高壓在周邊及全身臟俯的高血流動力狀態,慢性給予propranolol合併octreotide治療時,雖亦能有效的降低門脈壓並矯正門脈高壓的大部分高血流動力狀態,但似乎並未再提供更多的治療效應。
在我們的研究中發現無論單獨慢性給予isosorbide dinitrate或octreotide,皆能降低PVL大白鼠之門脈壓,並改善門脈高壓所形成之高血流動力狀態,而慢性給予octreotide合併isosorbide dinitrate治療,可能在降低門脈壓及矯正高血流動力狀態上提供了部分較具單獨給藥更有利的治療效果。
給予單一劑量10 mg/kg lanreotide-SR後一週,可有效的降低PVL大白鼠之門脈壓,與未給藥組有顯著之差異,lanreotide-SR可能是一個極具潛力之長效門脈高壓治療藥物,但其療效及影響仍須有更進一步的研究來加以探討。
Portal hypertension is a major complication of chronic liver disease. In Taiwan, liver diseases rank as a leading cause of mortalities. In portal hypertension patients, variceal bleeding is one of the main causes of death. The treatment of portal hypertension or its complication, variceal bleeding, has long been the focus of surgeons as well as physicians involved.
Tetrandrine is a calcium channel antagonist with reported anti-hypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The first part of study aimed to investigate the hemodynamic effects of chronic tetrandrine treatment on portal hypertensive rats. After 8 days treatment of tetrandrine reduced portal venous pressure and alleviated splanchnic hyperaemia in portal hypertensive rats, without affecting the portal systemic shunting.
Octreotide is an effective portal hypotensive drug in the control of variceal bleeding. The second part of study was undertaken to investigate the hemodynamic effects of octreotide and tetrandrine, alone or in combination, in portal hypertensive rats. The portal venous pressure and portal tributary blood flow were significantly reduced, while portal tributary and renal vascular resistances significantly enhanced, by octreotide, tetrandrine, or octreotide plus tetrandrine in portal hypertensive rats, as compared to vehicle group. After long-term administration of octreotide, tetrandrine, or octreotide plus tetrandrine led to portal hypotensive effects in portal hypertensive rats, but octreotide alone exerted better anti-hyperdynamic effects as compared to tetrandrine alone. Combination of octreotide and tetrandrine offered no major beneficial anti-hyperdynamic effects as compared to octreotide alone.
The third part of study was undertaken to investigate the hemodynamic effects of octreotide and propranolol, alone or in combination, in portal hypertensive rats. After long-term administration of octreotide, propranolol, or octreotide plus propranolol led to portal hypotensive and anti-hyperdynamic effects in portal hypertensive rats. Octreotide treatment alone resulted in better anti-hyperdynamic profiles then propranolol treatment alone. The combination of octreotide and propranolol, despite lack of synergistic or additive portal hypoetnsive and anti-hyperdynamic effects as compared to either drug alone, corrected portal venous pressure, portal tributary as well as hepatic aryerial blood flow, hepato-collateral, renal and systemic vascular resistances as well as cardiac index toward those in sham-operated rats.
The fourth part of study was undertaken to investigate the hemodynamic effects of octreotide and isosorbide dinitrate, alone or in combination, in portal hypertensive rats. After long-term administration of octreotide, isosorbide dinitrate, or octreotide plus isosorbide dinitrate led to portal hypotensive and anti-hyperdynamic effects in portal hypertensive rats. The combination of octreotide and isosorbide dinitrate, maybe offered some synergistic or additive portal hypoetnsive and anti-hyperdynamic effects compared to either drug alone.
Lanreotide-SR is a long-term somatostatin analogue. The final part of study aimed to investigate the portal hypotensive effects of chronic lanreotide-SR treatment on portal hypertensive rats. When 7 days after single dose of lanreotide-SR treatment, portal venous pressure in portal hypertensive rats was reduced. Lanreotide-SR maybe can offered longer portal hypotensive effects compared to the other drugs, now be used.



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