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Studies of non-investigate evaluation and development of therapy for ischemic injury of the liver using new technic of near-infrared specroscopy

近红外光谱新技术非研究评价缺血性肝损伤治疗方法的研究

基本信息

批准号：
07457253
负责人：
DOHI Kiyouhiko
金额：
$ 4.48万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Near-infrared spectroscopy (NIRs) was applied to rat liver for assessing nitric oxide (NO) synthesis and tissue oxygenation as a means of monitoring the rejection response and ischemic injury following liver transplatation. 1. NIRs was performed on the grafts in recipients, and the relative changes in nitrosyl-Hb, oxy-Hb, and oxidized cytochrome oxidase (Cyt.aa_3) were obtained. A significant rise in the level of nitrosyl-Hb was detected from the early phase of acute rejection in the untreated allogeneic group, and the increase was suppessed by deoxy-spergualin treatment. NO synthesis was also increased after long cold preservation in syngeneic liver transplants until day 3. Our NIRs method have a sensitivity to detect NO in the tissues at the level over 10^<-4>M NO,which was analyzed by use of in vivo assay using a spontaneous NO releaser (FK409). Levels of oxy-Hb and oxidized Cyt.aa_3 in the untreated allogeneic group were significantly decreased when parenchymal disorder was confirmed histologically, compared with those in syngeneic group, which remained constant. Thus, our NIRs technique was shown to be capable of assessing simultaneously both the immune resoponse and the degree of immune-induced destruction of graft tissue following liver transplantation through monitoring of NO synthesis and tissue oxygenation. 2. We developed a new rinse solution containing nafamostat mesilate (NM) (a serine protease inhibitor), and NM rinse and Kuppfer cell blockade exert synergistic effect in preventing ischemic injury in cold-preserved liver transplantation. We also reported that livers from fasted rats acquire tolerance to ischemic injury following transplantation. We examined heat shock protein (GRP78, HPS70) and TNF alpha section into the ascitic fluid of fasted rats is markedly suppressed. These findings suggest that induction of cytoprotective substances in the liver may contribute to the tolerance to ischemic injury.

应用近红外光谱(NIRS)检测大鼠肝脏一氧化氮(NO)合成和组织氧合情况，作为监测肝移植后排斥反应和缺血性损伤的手段。1.对受体移植物进行近红外光谱分析，观察移植肾组织亚硝基-Hb、氧合-Hb和氧化细胞色素氧化酶(Cyt.aa_3)的相对变化。在未治疗的同种异体移植组中，从急性排斥反应早期开始，亚硝基-Hb水平显著升高，这种升高可被脱氧精原鸟苷治疗所抑制。同种异体肝移植冷保存至第3天，NO合成也增加。我们的NIRS方法对检测组织中的NO水平超过10^&lt；-4&gt；M NO具有敏感性，这是使用自发的NO释放剂(FK409)进行体内分析的结果。当组织学证实实质功能紊乱时，未治疗同种异体组的oxy-Hb和氧化Cyt.aa3水平显著低于同种异体组，而同种异体组无明显变化。因此，我们的NIRS技术被证明能够通过监测NO合成和组织氧合来同时评估肝移植后的免疫应答和免疫诱导的移植组织破坏的程度。2.我们研制了一种含有丝氨酸蛋白酶抑制剂甲磺酸那法莫他(NM)的新型冲洗液，NM冲洗液与Kuppfer细胞阻断液在预防冷保存肝移植缺血损伤方面具有协同作用。我们还报道，禁食大鼠的肝脏在移植后获得了对缺血损伤的耐受性。我们检测了热休克蛋白(GRP78、HPS70)和肿瘤坏死因子α段进入腹水的禁食大鼠明显受到抑制。这些发现提示，肝脏中细胞保护物质的诱导可能有助于对缺血损伤的耐受。