利用 Verapamil 引發斑馬魚胚胎心衰竭模式並探討臨床心衰竭用藥 Dapagliflozin 和 Valsartan 之成效與機制
本研究利用 Verapamil 誘導斑馬魚胚胎心衰竭模式,並探討 Dapagliflozin 對斑馬魚胚胎表皮離子細胞的調控機制,以加深對 SGLT2 inhibitors 機制的了解。受精後第四天的斑馬魚在暴露於Verapamil 24小時後,除了抑制卵黃囊吸收以及造成心包膜水腫以外,對心臟整體功能(HR, EDV,ESV, SV, EF, CO)具負面影響。以粒線體染劑標記離子細胞,發現Verapamil使其密度上升,使用掃描式電子顯微鏡觀察,則可看到離子細胞頂端開口有明顯的萎縮,影響到正常功能。以抗體標記染色的方式檢測不同離子細胞亞型,顯示 Dapagliflozin 使富含 Na⁺-K⁺ ATPase 的 HR 細胞和富含 H⁺-ATPase 的 NaR 細胞密度上升。同時,心臟功能診斷標誌物的 mRNA 水平(naap, nppb,gata4, vmhc)暴露於Verapamil後上升,促進離子細胞代償性上調。
大「逆」不道—局部逆境下植物體內傳訊與物質分配機制
When a leaf of a plant encounters stress, how does the plant convey the stress signal to other tissues and manage nutrient distribution? This field of study has been largely unexplored. However, the unique interconnected frond structure of Lemna trisulca, along with the use of a divided Petri dish, is very suitable for handling localized stress and investigating the mechanisms of intracellular signaling and nutrient distribution. Research has shown that when the mother leaf experiences localized stress, it releases healthy daughter leaves to minimize collateral damage to the daughter leaves. Conversely, when the daughter leaves face localized stress, the mother leaf chooses to retain them and continues supplying them with nutrients to support their survival. In-depth studies revealed that stressed daughter leaves accumulate Reactive Oxygen Species (ROS), triggering nutrient distribution by sending a distress signal to the mother leaf. This prompts the mother leaf to use Ca2+ as a signaling molecule to deliver nutrients to the daughter leaves. Selective detachment is regulated and triggered by the interaction between Ca2+ and ROS within the mother leaf. When the mother leaf undergoes stress, Ca2+ acts upstream to induce ROS accumulation at the nodes, sending a unidirectional detachment signal to the daughter leaves. This causes ROS accumulation at the daughter leaf nodes, inducing detachment and thereby reducing the collateral damage the daughter leaf could experience due to the mother leaves.