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目的缺血再灌注损伤(IRI,ischemia/reperfusion injury)对于供体心脏是有害的。其机制与在急性或慢性移植失败过程中炎症反应达到高峰有关。多奈哌齐,一个乙酰胆碱酯酶抑制剂,可以通过抑制炎症反应从而保护移植术后的供体心脏。方法我们对Lewis大鼠进行了同种心脏移植,术后对接受移植的大鼠给予单剂量多奈哌齐(donepezil,DO),结果提示多奈哌齐可以预防急性或慢性移植失败。结果初次给药24小时后,多奈哌齐可以有效抑制细胞因子(TNF,IL-1β,IL-6)释放,CD11b/18阳性细胞筛选及心肌细胞凋亡。DO给药组的术后1个月存活率较其它组高(P<0.05);DO给药组的FS值也较其它组高(P<0.05)。给药组的胶原蛋白纤维化体积分数也明显降低(P<0.05)。结论我们的动物研究提示给予受体DO治疗可以保护供体心脏免于炎症及炎症介导的一系列病理生理反应,提示DO可以作为一个新的,可行的供体心脏保护的有效药物。
Purpose Ischemia / reperfusion injury (IRI) is detrimental to the donor’s heart. The mechanism is related to the peak of inflammatory reaction in the process of acute or chronic transplantation failure. Donepezil, an acetylcholinesterase inhibitor, protects the donor’s heart after transplantation by inhibiting the inflammatory response. Methods We performed allograft heart transplantation in Lewis rats. After transplantation, a single dose of donepezil (DO) was given to the transplanted rats. The results suggested that donepezil could prevent acute or chronic graft failure. Results Donepezil can effectively inhibit the release of cytokines (TNF, IL-1β, IL-6), CD11b / 18 positive cells and cardiomyocyte apoptosis 24 hours after the first administration. Compared with the other groups, the survival rate of DO administration group was higher than that of other groups (P <0.05). The DO value of DO administration group was also higher than other groups (P <0.05). The collagen fibrosis volume fraction in the treated group was also significantly reduced (P <0.05). Conclusions Our animal studies suggest that administration of DO may protect donor hearts from a series of pathophysiological responses mediated by inflammation and inflammation, suggesting that DO may serve as a new and viable drug for cardioprotection in donor hearts.