Cai Songjie, Ichimaru Naotsugu, Zhao Mingyi, Fujino Masayuki, Ito Hidenori, Ota Urara, Nakajima Motowo, Tanaka Tohru, Nonomura Norio, Li Xiao-Kang, Takahara Shiro
1 Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. 2 Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan. 3 AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. 4 SBI Pharmaceuticals Co., Ltd., Tokyo, Japan. 5 Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
Transplantation. 2016 May;100(5):1032-40. doi: 10.1097/TP.0000000000001079.
One of the major events in ischemia-reperfusion (I/R)-induced heart injury in cardiac transplantation is the generation of reactive oxygen species. We hypothesized that a novel preservation solution called SBI-SEIIKU II (SS-II) contains 3 antioxidant reagents: L-cysteine, glycine, ascorbic acid/ascorbic acid-2-phosphate magnesium, which can block the generation of reactive oxygen species to result in a prolongation of the cold storage time via attenuating I/R injury.
C57BL/6CrSlc(B6) mice underwent syngeneic mice heterotopic heart transplantation, and the animals were derived into 3 groups: recipients with nonpreserved grafts (control group), recipients with grafts preserved in histidine-tryptophan-ketoglutarate (HTK) for 24 and 48 hours (HTK group), and recipients with grafts preserved in SS-II for 24 and 48 hours (SS-II group).
After 48 hours of preservation, there were no grafts that survived in the HTK group; however, the SS-II group had a high survival rate. After 24 hours of preservation, SS-II decreased the oxidative damage, myocardial apoptosis, and the infiltration of macrophages and neutrophils in the cardiac grafts in the early phase and suppressed the development of myocardial fibrosis in long-term grafts compared with HTK.
The SS-II prolongs the acceptable cold storage time and protects the myocardium from I/R injury via inhibiting oxidative stress-associated damage. We believe that this novel preservation solution may be simple and safe for use in the clinical transplantation field.
心脏移植中缺血再灌注（I/R）诱导的心脏损伤的主要事件之一是活性氧的产生。我们假设一种名为SBI-SEIIKU II（SS-II）的新型保存液含有3种抗氧化剂：L-半胱氨酸、甘氨酸、抗坏血酸/抗坏血酸-2-磷酸镁，它们可以通过减轻I/R损伤来阻断活性氧的产生，从而延长冷保存时间。
C57BL/6CrSlc（B6）小鼠接受同基因小鼠异位心脏移植，动物被分为3组：接受未保存移植物的受体（对照组）、接受在组氨酸-色氨酸-酮戊二酸（HTK）中保存24小时和48小时的移植物的受体（HTK组），以及接受在SS-II中保存24小时和48小时的移植物的受体（SS-II组）。
保存48小时后，HTK组没有存活的移植物；然而，SS-II组有较高的存活率。与HTK相比，保存24小时后，SS-II在早期减少了心脏移植物中的氧化损伤、心肌细胞凋亡以及巨噬细胞和中性粒细胞的浸润，并在长期移植物中抑制了心肌纤维化的发展。
SS-II延长了可接受的冷保存时间，并通过抑制氧化应激相关损伤保护心肌免受I/R损伤。我们认为这种新型保存液在临床移植领域的使用可能简单且安全。
