Cheng F, Feng L, Li S, Tan J, Cao L, He Y, Ye Z, Li Y
Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, People's Republic of China.
Transplant Proc. 2006 Sep;38(7):2210-3. doi: 10.1016/j.transproceed.2006.06.100.
Major histocompatability complex class I chain-related antigen A, B (MICA, B) functions as ligands for human NKG2D receptors, which may play a role in graft rejection and cellular stress. In this study we explored the effect of ischemia/reperfusion injury (IRI) on the expression of H60 and RAE-1 (MICA, B homologues) in mice to study the protective effect of Yisheng injection (YS), an herbal preparation developed from traditional Chinese medicine.
Male BALB/c mice were divided into sham, ischemic, and YS-treated groups using 90 minutes of left liver lobe ischemia. Sham control mice underwent the same operation, but without vascular occlusion. In the treated group, YS (20 mg/kg) was given before ischemia and after reperfusion for 7 days. Liver samples collected at 7 days postoperation were used for real-time quantitative polymerase chain reaction analysis, Western blotting, and immunohistochemical assays.
Compared with the sham group, H60 and RAE-1 mRNA levels were increased by sevenfold and 4.5-fold in the ischemic group, respectively. After YS treatment, they were reduced by 76% and 70%, respectively. Western blotting and immunohistochemical assays showed that there was absent or faint H60 and RAE-1 expression in sham liver, but they were apparently increased in ischemic liver; however, the expressions were significantly decreased in the presence of YS.
Hepatic IRI significantly increased H60 and RAE-1 expression in mouse liver. YS treatment effectively reduced this increase, seeming to attenuate NKG2D-ligand-mediated immune responses caused by IRI. This may suggest a new concept to prevent IRI and graft rejection.
主要组织相容性复合体I类链相关抗原A、B(MICA、B)作为人类NKG2D受体的配体,可能在移植排斥和细胞应激中发挥作用。在本研究中,我们探讨了缺血/再灌注损伤(IRI)对小鼠H60和RAE-1(MICA、B同源物)表达的影响,以研究中药制剂益盛注射液(YS)的保护作用。
雄性BALB/c小鼠采用左肝叶缺血90分钟的方法分为假手术组、缺血组和YS治疗组。假手术对照组小鼠接受相同手术,但不进行血管阻断。在治疗组中,在缺血前和再灌注后7天给予YS(20mg/kg)。术后7天收集的肝脏样本用于实时定量聚合酶链反应分析、蛋白质印迹法和免疫组织化学分析。
与假手术组相比,缺血组H60和RAE-1 mRNA水平分别增加了7倍和4.5倍。YS治疗后,它们分别降低了76%和70%。蛋白质印迹法和免疫组织化学分析显示,假手术肝脏中不存在或仅有微弱的H60和RAE-1表达,但在缺血肝脏中明显增加;然而,在YS存在的情况下,表达显著降低。
肝脏IRI显著增加了小鼠肝脏中H60和RAE-1的表达。YS治疗有效地降低了这种增加,似乎减弱了IRI引起的NKG2D配体介导的免疫反应。这可能为预防IRI和移植排斥提出了一个新的概念。