Department of Pharmacy, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, PR China.
Phytomedicine. 2008 Nov;15(11):923-31. doi: 10.1016/j.phymed.2008.09.003.
A new standardized Ginkgo extract (ginaton) destined for i.v. injection was investigated in rats for its protective effect on renal ischemia/reperfusion injury. We report on the elucidation of the downstream mechanism of action of JNK on the renal ischemia/reperfusion injury, which can be explained as the decrease in JNK phosphorylation at 20 min and c-Jun phosphorylation (Ser63/73) at 3h after renal ischemia. At the same time, ginaton attenuated the increased expression of FasL at 3h and caspase3 immunoreactivity at 6h after renal ischemia. Furthermore, ginaton significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that ginaton could suppress the JNK-c-Jun-FasL-caspase3 signaling cascade, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by JNK signal pathway.
一种新的标准化银杏提取物（金纳多），旨在用于静脉注射，在大鼠中研究其对肾缺血/再灌注损伤的保护作用。我们报告了 JNK 在肾缺血/再灌注损伤中的下游作用机制，这可以解释为肾缺血后 20 分钟 JNK 磷酸化和 c-Jun 磷酸化（Ser63/73）减少。同时，金纳多可减轻肾缺血后 3 小时 FasL 表达增加和 caspase3 免疫反应性。此外，金纳多可显著减少肾缺血/再灌注诱导的肾小管上皮细胞凋亡，减轻肾缺血/再灌注损伤。这些结果表明，金纳多可能通过抑制 JNK-c-Jun-FasL-caspase3 信号级联反应，抑制肾缺血/再灌注诱导的肾小管上皮细胞凋亡，从而保护肾脏，这意味着抗氧化剂可能是通过抑制 JNK 信号通路诱导的细胞外凋亡信号通路，预防缺血/再灌注损伤的一种潜在有效的药物。
