臺灣博碩士論文加值系統

對肛門內括約肌鬆弛功能的調控是治療若干肛門直腸疾病成功與否的關鍵。本論文以傳統中醫溫灸中局部溫熱刺激及中藥成分吳茱萸次鹼來達到鬆弛肛門內括約肌的目的並探討其機轉。
我們利用水傳導的肛門壓力測量系統來監測肛門壓力。動物實驗時是用電熱棒作為局部溫熱刺激的熱源，置於紐西蘭白兔右側後膝窩正中（委中穴）距離皮膚表面一公分處。溫熱刺激一分鐘後白兔之肛門內括約肌活性（包括基礎壓力、相位收縮壓力及收縮波頻率）明顯受到抑制。此效應不因先前加入交感、副交感抑制劑 Atropine, Phentolamine, Propranolol而受影響。但如先前加入一氧化氮合成之抑制劑Ng-nitro-L-arginine methyl ester (L-NAME) 則鬆弛效應消失。若於L-NAME之前先加入L-arginine則鬆弛效應會再出現，然而D-arginine則無此作用。
在人體實驗中則是以溫敷包置於右側臀下皮膚皺折正中處（承扶穴）的皮膚上。溫熱刺激引起之反應與病人本身肛門內括約肌所處的功能狀態有關；溫熱刺激三分鐘後有超短波的病人其超短波波幅會明顯減小，而無超短波之病人則肛門基礎壓力會明顯下降。此外對溫熱刺激有反應組病人的基礎壓力比沒反應組來得高，肛門內括約肌活性愈高的病人組（例如肛裂患者）對溫熱刺激有反應的比例愈高。
為研究吳茱萸次鹼對肛門內括約肌之作用，我們取下紐西蘭白兔的肛門內括約肌條在組織溶液 (organ bath)中作實驗。結果顯示吳茱萸次鹼會使內括約肌條鬆弛，此反應不因加入L-NAME, guanylate cyclase及adenylate cyclase之抑制劑methylene blue及N-ethylmaleimide而受影響。其次黏膜層及其下組織存在與否亦不影響內括約肌條之反應。但若加入鈣離子阻斷劑 (nifedipine) 及無鈣狀態下加ethylene diaminetetraacetic acid (EDTA)則會抑制吳茱萸次鹼之肌肉鬆弛效應。當利用人類之肛門內括約肌條作實驗，吳茱萸次鹼可以引發比白兔內括約肌條更明顯的鬆弛反應。
由本實驗結果我們發現局部溫熱刺激會經由非交感非副交感 (NANC) 神經元釋出之一氧化氮造成肛門內括約肌之鬆弛；而吳茱萸次鹼則經由對肛門內括約肌細胞鈣離子之調控使其放鬆。這兩項發現展示傳統中醫藥對肛門內括約肌功能調控的模式，並提供臨床上對肛門內括約肌壓力異常增高疾病的另一治療選擇。

Modulation the relaxant function of the internal anal sphincter (IAS) plays a key role in successful treatment of several anorectal disorders. It is our purpose to demonstrate whether and how the traditional Chinese medicine "moxibustion" -- local somatothermal stimulation and one of the ingredients of a Chinese medicinal herb, rutaecarpine, modulate the function of internal anal sphincter.
The activity of internal anal sphincter was measured by using continuously water perfused open-tip manometric method. In animal study, local somatothermal stimulation was achieved by applying an electroheating rod 1 cm away and above the skin area over center of the right side popliteal fossa (Acupoint Weuzhong, BL-40, 委中穴) of New Zealand white rabbits. The activity of IAS, in terms of basal tonic pressure, phasic contraction pressure and peak-to-peak interval were significantly suppressed about one minute after thermal stimulation. The local somatothermal stimulation induced IAS-relaxation was not inhibited by pretreatment with atropine, propranolol, phentolamine. However, pretreatment with L-NAME (a nitric oxide synthesis inhibitor) blocked the IAS relaxation, which was reversed by pretreatment with L-arginine, but not by D-arginine.
In clinical study, a heat pad was applied to the skin area at the middle of right side infragluteal skin crease (Acupoint Chengfu, BL-36, 承扶穴). The human IAS responded to local somatothermal stimulation differently according to the functional status of the IAS; in patients with ultraslow wave the amplitude of ultraslow wave began to decrease about three minutes after thermal stimulation, whereas, in those without ultraslow wave, the tonic pressure dropped. Besides, the higher the anal tone, the higher the percentage of heat-sensitive individuals in each group of the patients. The basal tonic pressure of the heat-sensitive individuals was significantly higher than that of the nonresponding patients.
IAS strips from rabbits were used for studying the muscular relaxation effect of rutaecarpine. Rutaecarpine produced a concentration-dependent muscular relaxation effect which was not affected by treatment with L-NAME (a nitric oxide synthase inhibitor), methylene blue (a guanylate cyclase inhibitor), N-ethylmaleimide (an adenylate cyclase inhibitor), or by removal of the mucosa and submucosa tissue. Pretreatment with nifedipine (a calcium channel blocker) or extracellular Ca+2 removal by ethylenediaminetetraacetic acid (EDTA) greatly attenuated the relaxation effect. In experiments using strips from human internal anal sphincter, an even more prominent relaxation effect was shown.
We conclude that local somatothermal stimulation inhibits the IAS motility through the activation of nonadrenergic noncholinergic neural release of nitric oxide, whereas the muscular relaxation effect of rutaecarpine is not related to NO-cGMP pathway, instead calcium ion might play an important role. Models of manipulation the function of internal anal sphincter by Chinese medicine - moxibustion and ingredient of Chinese medicinal herb, rutaecarpine, are successfully demonstrated and shed insight into clinical implications for those anorectal disorders with hyperactive anal tone.

封面
目錄
中文摘要
英文摘要
第壹章 緒論
第貳章 局部溫熱刺激對白兔肛門內括約肌之調控
2-1 前言
2-2 實驗方法
2-2-1 動物及肛門壓力測量
2-2-2 局部溫熱刺激
2-2-3 肛門內括約肌鬆弛機轉之探討
2-3 實驗結果
2-3-1 局部溫熱刺激對肛門內括約肌之鬆弛作用
2-3-2 局部溫熱刺激引發肛門內括肌鬆弛之機轉
2-4 圖與表
第參章 局部溫熱刺激對人體肛門內括約肌之調控
3-1 前言
3-2 實驗方法
3-2-1 病人及方法
3-2-2 局部溫熱刺激
3-2-3 肛門直腸壓力監測
3-3 實驗結果
3-3-1 肛門壓力測量結果
3-3-2 肛門內括肌對局部溫熱刺激之反應
3-4 圖與表
第肆章 吳茱萸次鹼肛門內括約肌之鬆弛作用及機轉
4-1 前言
4-2 實驗方法
4-2-1 白兔肛門內括約肌條之分離
4-2-2 內括約肌肌條收縮活性之記錄
4-2-3 吳茱萸次鹼肌肉鬆弛作用
4-2-4 吳茱萸次鹼肌肉鬆弛作用之機轉
4-2-5 吳茱萸次鹼在人類肛門內括約肌之作用
4-3 實驗結果
4-3-1 吳茱萸次鹼肌肉鬆弛作用
4-3-2 吳茱萸次鹼肌肉鬆弛作用之機轉
4-3-3 吳茱萸次鹼在人類肛門內括約肌之作用
4-4 圖與表
第伍章 討論
第陸章 結論與展望
參考文獻
附錄 本研究已發表之期刊論文

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