| 摘要: | 癲癇；是一種中樞神經系統 (CNS) 疾病它會導致頻繁身體不由自主全身顫抖發作，若不妥善治療最後很容易導致心臟猝死。 由於癲癇發作會引發大腦產生突發性劇烈電流活動，導致行為、運動或感覺暫時改變。 超極化活化的環核苷酸門控 (HCN) 通道家族包含在心臟和神經系統中表達的四個成員 (HCN1-4)。 此外；心臟的節律活動主要由起搏器通道、環核苷酸門控 4 型 (HCN4) 通道控制。 過去幾年裡有新研究的臨床數據表明，功能失調的 HCN 通道可能在癲癇中導致病源發生。然而 HCN 通道與癲癇發作之間的潛在連接機制仍不清楚。之前的研究顯示煙酰胺單核苷酸（NMN）具有保護心臟與預防心血管疾病和抗衰老能力而聞名。然而，癲癇發生後多數死於心律不齊而導致心臟猝死，對於 NMN 是否對癲癇與心臟疾病有保護作用直到如今並不清楚。我們希望透過這一次的實驗知道癲癇發生後與心臟連結的病症狀況，再透過 NMN 的使用讓我們能了解它對癲癇與心臟的保護機制在哪？藉此希望透過這一次的實驗我們的研究使用 4 至 6 個月大的成年 A、B 斑馬魚通過給予服用保健用品接受 500μg 與 250μg NMN 40 分鐘。 『結果顯示不同的給予 NMN 劑量的斑馬魚暴露於 10mM 戊四唑 (PTZ) 20 分鐘後的癲癇發作階段。爾後；通過 Real-time-PCR 看 (HCN4) 在心臟細胞的 mRNA 的表現量來了解其相關的穩定度，再透過 ELISA 來知道 ROS 表達蛋白質和基因表達水平，神經細胞的不穩定也會讓心臟不穩定，癲癇也會讓自由基升高而導致心臟衰竭猝死。在實驗過程中；我們的確認了 NMN 使神經元更能預防癲癇發作。我們的結果表現， NMN 可能成為未來治療癲癇的天然物的良好選擇。
Epilepsy is a central nervous system (CNS) disorder that leads to frequent involuntary full-body tremors. If left untreated, it can ultimately result in sudden cardiac arrest. Epileptic seizures trigger sudden intense electrical activity in the brain, causing temporary changes in behavior, movement, or sensation. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel family, comprising four members expressed in both the heart and nervous system (HCN1-4), plays a role. Additionally, the cardiac rhythm relies primarily on pacemaker channels, specifically the hyperpolarization-activated cyclic nucleotide-gated type 4 (HCN4) channels.
Recent clinical data from new research suggest that dysfunctional HCN channels might contribute to the onset of epilepsy. However, the potential mechanisms linking HCN channels to epileptic seizures remain unclear. Previous studies have highlighted Nicotinamide Mononucleotide (NMN) for its reputed heart-protective, cardiovascular disease preventive, and anti-aging properties. However, whether NMN offers protection against epilepsy and cardiac diseases post-seizures, which often result in arrhythmia and sudden cardiac arrest, remains uncertain.
Through this experiment, we aim to understand the post-seizure symptoms connecting epilepsy with the heart and explore NMN's protective mechanisms on epilepsy and the heart. In this study, adult A and B zebrafish, aged between 4 to 6 months, will receive health supplements containing 500μg and 250μg NMN, respectively, administered 40 minutes prior to exposure to 10mM pentylenetetrazole (PTZ) for 20 minutes. Subsequently, we will analyze the results using Real-time PCR to assess mRNA expression levels of HCN4 in cardiac cells for stability, and ELISA to determine ROS protein and gene expression levels. The instability of nerve cells may affect heart stability, while elevated free radicals due to epilepsy could lead to heart failure and sudden death.
Throughout the experiment, we confirmed that NMN enhances neuronal resistance to epileptic seizures. Our findings suggest that NMN could be a promising natural treatment option for epilepsy in the future. |
