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Title: | 肢體刺激誘發神經反射所引起之特異性血流變化 Neural reflex-mediated specific blood flow change after limb stimulation |
Authors: | Chung-Shin Huang 黃忠信 |
Advisor: | 蔡元奮(Yuan-Feen Tsai) |
Co-Advisor: | 王淑芬(Shwu-Fen Wang) |
Keyword: | 軸突反射,局部熱充血反應,電刺激,皮膚血流,交感神經反射, axon reflex,local thermal hyperemia,electrical stimulation,skin blood flow,somato-sympathetic reflex, |
Publication Year : | 2013 |
Degree: | 博士 |
Abstract: | 動物為了生存所需,會經由神經系統的作用不斷對內外環境的變動進行監控與調適。其對於外來刺激所產生的反應有很大的部分與血流量的改變有關。這些反應有些是廣泛性的,有些則具有局部特異性。如能釐清各神經系統之間刺激反應的對應關係,以及其所產生的特異性血流量改變,就有可能藉由人為施予物理性的刺激,來產生預期的反應,以達到調控神經功能與改善生理功能的目的。
本研究嘗試建構此種刺激反應研究所需的方法學,並利用其驗證某些刺激反應關聯性的規則。研究的檢測方法係採用局部熱充血反應(local thermal hyperemia)測試來觀察加熱後的局部血流增加現象,此反應被認為與感覺神經的功能有關,且受到交感神經活性與一氧化氮基礎濃度所調控。治療的方法則採用目前已廣泛應用於臨床與研究的電刺激(electrical stimulation),觀察電刺激對目標部位所產生的血流量改變情形。 以往運用的局部熱充血反應測試採用隨機選取的測量部位來進行,其加熱時間需超過30分鐘。雖然採用最大血管擴張量(maximal dilatation)來校正各部位微血管密度的差異性,但採用單點式雷射杜普勒血流計(single-point laser Doppler flowmetry)量測的再測信度(reproducibility)不佳。本研究改良上述之缺點,使用單點式雷射杜普勒血流計,在同一個部位進行測試,且加熱時間縮短為5分鐘。結果顯示,在只間隔45分鐘的同一測期裡,針對前臂背面同一個部位進行重複測試,其軸突反射熱充血反應具有良好的再測信度。此外,本研究進一步發現,如測試部位以預先界定的規則來重新定位,在間隔一至三日後重複再測試,則短時間局部加熱所引發的軸突反射充血反應仍具有良好的再測信度。但在其右前臂與左前臂的局部熱充血反應具有不同的再測信度,而延長環境適應的時間則可提高再測信度。 上下肢的解剖結構具有對稱性,為了維持肢體的正常移動,上下肢之間有非常即時而良好的互動協調。因此,本研究第二部份係採用此種具有再測信度而使用方便的測試方法,以上下肢之間的刺激反應,來探討是否兩者之間存在特異性的刺激與反應關聯性,以及其對應的規則為何。方法是利用辣椒素紗布敷貼於人體單側小腿皮膚來誘發局部發炎反應,並使用雷射杜普勒血流計測量兩側前臂解剖上的對應部位與非對應部位兩處的局部熱充血反應。結果顯示右小腿的辣椒素刺激會增強右前臂對應部位的局部熱充血反應,而左小腿的辣椒素刺激則對左右兩側前臂的局部熱充血反應都不影響。推測此種反應可能是經由體交感神經反射,使交感神經活性提高,進而影響軸突反射強度。此結果顯示上下肢之間可能存在特異性的刺激反應作用,其作用不僅具有解剖上特異性之對應關係,且左右側的反應並不相同。 為探討人為施加刺激可否在上下肢對應部位產生調整生理功能的作用,本研究的第三部份採用大鼠兩側後肢缺血60分鐘,於24小時之後在單側前肢進行30分鐘不同頻率的電刺激(3、45或 45 Hz),以雷射杜普勒影像儀觀察兩側後肢體表血流的變化。結果發現前肢電刺激可以造成後肢特定部位的血流量產生特異性的改變。以125 Hz電刺激左前肢可改善兩側後肢血流,而電刺激右前肢則對兩側後肢的血流量都無作用。不同頻率電刺激與電刺激在不同側前肢所產生的後肢血流改變效應不同。推測其效應可能來自體交感神經反射,使後肢特定部位的交感神經張力下降,進而增加血流。 綜合以上實驗結果,本研究改良了局部熱充血反應測試方法,不但大幅減少檢測所需之時間,亦提高其再測信度,可用來評估單純由神經媒介的軸突反射。此方法也藉由辣椒素體表刺激後,於上下肢之間的解剖對應部位得到局部熱充血反應量的顯著改變。因此,今後在進一步研究確認此種改變是經由體交感神經反射的作用後,此方法未來可針對有興趣的目標部位進行測試,以了解該部位的交感神經活性之變化。本研究也發現上肢電刺激可以在下肢產生特異性血流改變,故亦有機會應用在分析體交感神經反射之刺激反應部位的關聯性。 經由發現局部熱充血反應與電刺激之較佳參數,本研究結果顯示這兩項技術可以用來檢測與驗證特異性的體表刺激與反應規則。在進一步探究以確認其刺激反應是經由體交感神經反射的作用後,可利用此等技術繼續探討與建立刺激反應的對應規則,進而發展實用的標靶神經調節(targeted neuromodulation)技術,臨床上有潛力可運用於治療各種與神經與血液循環系統功能失調有關的疾病。 Animals adjust their physiological conditions through the nervous systems to accommodate the internal and external environmental challenges, and their stimuli-responses act according to certain mechanisms. The responses are majorly related to the changes of blood flow which are either generalized or specific. If the mechanisms of stimuli-responses could be clarified, we can use certain artificial physical stimuli to regulate the physiological functions through neural modulation. The previously used protocols of LTH tested the randomly selected recording sites and the heating time was longer than 30 min. Although the axon reflex (AR) flare has been normalized by maximal vasodilatation to adjust the spatial heterogeneity of capillary density, the reproducibility of previous method using single-point laser Doppler flowmetry (LDF) was poor. The results of this study demonstrated that single-point LDF is a reproducible technique of assessing AR flare on dorsal surface of the forearm twice with 45 min apart when the heating period is reduced to as short as 5 min and the recording sites are fixed. In addition, the AR flare induced by short local heating is reproducible with 1-3 days apart when the recording sites are relocated by a predefined rule. The reproducibility of LTH on the right forearm is different from that on the left forearm, and the increase of acclimation period can improve the reproducibility. The anatomical structures of upper and lower limb are symmetrical. There is timely and good coordination between upper and lower limbs to keep the free motion of limbs. In this study, the stimuli-responses between upper and lower limbs were investigated. Capsaicin epidermal stimulation was applied on the unilateral leg and LTH was measured by LDF on the corresponding and non-corresponding position of bilateral forearm. The results demonstrated that stimulation on the right leg enhanced the LTH response on the corresponding position of right forearm. Stimulation on the left leg did not affect the LTH response of bilateral forearm. This effect may be attributed to that the LTH response was enhanced by increased sympathetic tone which was mediated by somato-sympathetic reflex. These results showed that an anatomically specific stimulus-response may exist between upper and lower limbs. Electrical stimulation (ES) with 3, 45 or 125 Hz for 30 min was applied to unilateral forelimb 24 hrs after bilateral hindlimb ischemia for 60 min to explore whether this stimulation could adjust the physiological condition on the corresponding region of hindlimb. Laser Doppler imager was used to measure the blood flow change on bilateral hindlimb during and after ES. The results showed that ES on forelimb may induce specific blood flow change on specific region of hindlimb. ES with 125 Hz on left but not right forelimb could induce significant blood flow increase on bilateral hindlimb. It may infer that the blood flow increase may be attributed to the decreased sympathetic tone which was mediated by somato-sympathetic reflex. These results showed that short-heatng LTH method can be reproducible and be used to evaluate the simple nerve-mediated AR. Capsaicin stimulation induced a specific LTH change of the anatomical corresponding positions between upper and lower limb. Hence, after further verifying the response was mediated through somato-sympathetic reflex, this method can be used to evaluate the change of sympathetic activity on the region of interest. Finally, these results indicated that ES on forelimb may induce a specific blood flow change on hindlimb. Therefore, after further verifying the blood flow change is mediated through somato-sympathetic reflex, the topographical relationship of somato-sympathetic reflex may be established. These results suggested that the techniques of both LTH and ES can be used to investigate the specific rule of stimuli-responses after adopting better parameters. Therefore, they can be applied to further explore and establish the corresponding rules of stimuli-responses and to develop a targeted neuromodulation therapy with a potential to treat the disorders of nervous and blood circulatory system. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6344 |
Fulltext Rights: | 同意授權(全球公開) |
Appears in Collections: | 生理學科所 |
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