| 摘要: | 風者，善行而數變。又風者，百病之長，風邪中人，本皆表證，而人臥血歸於肝。肝主風，若肝血不足，呈現肝血虛時，則會產生肝陽上亢，或肝火上炎，而導致肝風內動。因此，風有內風如肝風內動，和外風如風邪外感。肝風內動的形成是來自於肝系統陰陽間的不平衡而引起，即興奮與抑制間的失衡其導致疾病的臨床特徵相當於現代醫學的發作性疾病如癲癇發作、神經病性疼痛和偏頭痛等。因此，本研究的目的是以癲癇發作和神經病性痛為例，探討中醫藥治療發作性疾病的療效和機轉。研究分為實驗一：以鉤藤和鉤藤鹼前治療三天，然後以卡英酸( kainic acid, KA 12 mg/kg)於Spragrue-Dawley（SD）大鼠腹腔注射誘發癲癇發作，KA注射後3小時時將大鼠犧牲取腦，觀察大鼠腦組織大腦皮質和海馬區域中cytokines包括interleukin-1β（IL-1β）、IL-6和tumor necrosis-α；mitogen activator protein kinase（MAPK）訊息路徑和nuclear factor-κB（NF-κB）活性的變化；實驗二：用4-0的鉻腸線於SD大鼠的右坐骨神經做寬鬆的結紮，建立慢性狹縮性損傷（chronic constriction injury, CCI）神經病性痛動物模型探討電針對神經病性痛的療效及機轉，即CCI神經病性痛大鼠之行為改變，以及大腦皮質和脊髓的Transient receptor potential vanilloid type 1 （TRPV1）和TRPV4的變化。結果：鉤藤與鉤藤鹼兩者都能減少癲癇發作和減少MAPK的c-Jun-N-Terminal Kinase phosphorylation (pJNK)表現；2 Hz和15 Hz電針都能減少CCI誘發輻射熱試驗的左─右潛伏期差、減少4℃冷板試驗的抬腳次數和增加von Frey試驗的克數，以及減少大腦皮質TRPV4的表現。
結論是鉤藤和鉤藤鹼兩者都有抗癲癇作用，癲癇發作急性期的抗癲癇作用與MAPK的JNKp訊息路徑有關。2 Hz和15 Hz電針都能減少CCI誘發神經病性疼痛，他們減少神經病性疼痛的機制可能是經由多途徑，並推測與大腦皮質的TRPV4表現有關。
The character of wind is quick and easy changes, and wind causes diseases are the most common, such as common cold. The blood returns to the liver during the sleepy. Wind is belong to liver system, thus, liver blood deficiency can produced ascendant hyperactivity of liver yang, or liver fire flaming upward resulting in liver wind. Therefore, wind divides into internal wind such as liver wind, and external wind such as common cold. Liver wind is resulting from imbalance between yin and yang in liver system, i.e. imbalance between excitation and inhibition, such as epileptic seizure, neuropathic pain and migraine etc., and these are identical paroxysmal disorders in modern medicine. Therefore, the purpose of the present study was to investigate therapeutic effect and mechanism of Chinese medicine treating paroxysmal disorders focus in epileptic seizure and neuropathic pain. The study divided into experimental one: using Uncaris rhynchylla (UR) and rhynchophylline (RP) pretreatment for three days, and then induced epileptic seizure by kainic acid (KA, 12 mg/kg) i.p. in the Sprague-Dawley (SD) rats. The rat was sacrificed and the brain was removed 3 h after KA administration. Cytokines including interleukin(IL)-1β, IL-6 and tumor necrosis factor-α, (TNF-α) and mitogen activator protein kinase (MAPK) signal pathway and nuclear factor-κB (NF-κB )were observed in the cerebral cortex and hippocampal brain tissues; experimental two: the chronic constriction injury (CCI)-induced neuropathic pain animal model was established in the SD rats by using 4-0 chromic gut ligated loosely in the right sciatic nerve, and then investigated the therapeutic effect and mechanism of electroacupuncture (EA) on neuropathic pain including behavior and transient receptor potential vanilloid type 4 (TRPV4) and TRPV1. The results: both UR and RP pretreatment can reduce epileptic seizures and the expression of c-Jun-N-Terminal Kinase phosphorylation (JNKp) of MAPK; both 2Hz and 15Hz EA could reduce withdraw latency difference of left-right hind-limbs in the radiant heat test, and could reduce lift legs counts in the 4℃ cold plate test, and also could increase gram number in the von Frey test. In addition, both 2Hz and 15Hz EA could reduce the expression of TRPPV4 in the cerebral cortex.
In conclusion, both UR and RP have anticonvulsive effect, and anticonvulsive effect has relationship to JNKp of MAPK signal pathways in acute seizure stage; both 2 Hz and 15 Hz EA can reduce CCI-induced neuropathic pain, the this effect of reducing neuropathic pain is mediated via multiple pathways, and suggesting cerebral TRPV4 is involved. |
