【作者】 马小娟；

【导师】 王红梅； 张建龙；

【作者基本信息】 新疆医科大学 ， 病理学及病理生理学， 2007， 硕士

【摘要】 目的:探讨肝缺血再灌注损伤时血清内毒素变化对心脏的影响及其可能的发生机制。方法:建立肝缺血再灌注损伤动物模型,选健康雄性Wistar大鼠56只,随机分为对照组(CTL组)、缺血30min组(I组)、缺血30min再灌注即刻组(I/R组)、缺血30min再灌注2h组(I/R2h组)、缺血30min再灌注4h组(I/R4h组)、缺血30min再灌注6h组(I/R6h组)和缺血再灌注4h预处理组(654-2组),每组8只。用BL-420生物信号采集系统来测定心功能,用偶氮显色法测定血清内毒素,用放射免疫法测定心肌组织胰岛素和胰岛素抗体,取心肌制备组织匀浆测丙二醛(MDA)、髓过氧化物酶(MPO)及乳酸。结果:心率(HR)在I组和I/R组明显下降,随着再灌注时间的延长开始回升,与I/R组比较差异有统计学意义(P＜0.05),但与对照组比较差异无统计学意义(P＞0.05);654-2组与对照组和I/R4h组比较,差异无统计学意义(P＞0.05)。左室收缩压(LVSP)在I组和I/R组下降,与对照组相比,差异有统计学意义(P＜0.05),在I/R2h组回升至正常水平,而在I/R4h组和I/R6h组明显下降,与对照组比较差异有统计学意义(P＜0.05);654-2组与对照组、I/R4h组比较,差异有统计学意义(P＜0.05)。左室舒张末期压力(LVEDP)在I/R4h组和I组比较明显上升,差异有统计学意义(P＜0.05),I/R6h组与各组相比差异均有统计学意义(P＜0.05);654-2组与对照组和I/R4h组比较明显下降,差异有统计学意义(P＜0.05)。左室内压最大上升速率(+dp/dtmax)虽在不同的组有所波动,但仅在I/R6h组与对照组、I组、I/R组和I/R2h组比较明显下降,差异有统计学意义(P＜0.05);654-2组与对照组和I/R4h组比较明显上升,差异有统计学意义(P＜0.05)。左室内压最大下降速率(-dp/dtmax)呈上升趋势,在I/R组、I/R6h组均和对照组比较明显上升,差异有统计学意义(P＜0.05);654-2组与对照组和I/R4h组比较明显下降,差异有统计学意义(P＜0.05)。血清内毒素的变化在不同组均与对照组比较明显增加,差异有统计学意义(P＜0.05),并且在I组和I/R组达到高峰,随着再灌注时间的延长,逐渐降低,但仍高于对照组(P＜0.05);654-2组与对照组和I/R4h组比较,差异有统计学意义(P＜0.05)。心肌组织中MDA自I组开始,各组含量明显增加,与对照组比较,差异有统计学意义(P＜0.05),在I/R2h组、I/R4h组、I/R6h组与I组和I/R组比较,差异有统计学意义(P＜0.05);654-2组与对照组和I/R4h组比较,差异有统计学意义(P＜0.05)。心肌组织中MPO在再灌注各组与对照组和I组比较明显增加,差异有统计学意义(P＜0.05);而再灌注各组间差异无统计学意义(P＞0.05);654-2组与对照组和I/R4h组比较,差异有统计学意义(P＜0.05)。心肌组织中乳酸的变化在I/R2h组、I/R4h组、I/R6h组分别与对照组、I组、I/R组比较明显增加,差异有统计学意义(P＜0.05);654-2组与对照组比较,差异无统计学意义(P＞0.05),但和I/R4h组比较明显下降,差异有统计学意义(P＜0.05)。胰岛素在心肌组织中的变化为I/R组与I组比较明显降低,差异有统计学意义(P＜0.05),而在I/R2h组明显升高,与I/R组比较,差异有统计学意义(P＜0.05),I/R4h组和I/R6h组分别与对照组、I组及I/R2h组比较,差异有统计学意义(P＜0.05);654-2组与对照组比较,差异无统计学意义(P＞0.05),但和I/R4h组比较,差异有统计学意义(P＜0.05)。而心肌组织胰岛素抗体在各组间差异均无统计学意义(P＞0.05)。结论:肝缺血再灌注损伤过程中,肠源性内毒素吸收入血及肝脏解毒功能的降低所致的内毒素血症是引起心脏功能、代谢和结构改变的始动环节之一;654-2在缺血再灌注损伤中具有一定的保护效应。更多还原

【Abstract】 Objective: To investigate the effect and mechanism of serum endotoxin on heart during liver I/R injury. Methods: A model of liver I/R injury was established by imitation. 56healthy Wistar male rats were randomly divided into 7 groups as following(n=8):the control group(CTL), simply ischemia 30min without reperfusion (I group), reperfusion following ischemia 30min (I/R group), 2 hours reperfusion following ischemia 30min (I/R2h group), 4 hours reperfusion following ischemia 30min (I/R4h group), 6 hours reperfusion following ischemia 30min (I/R6h group) and pretreatment group (654-2 group). The cardiac function were measured by BL-420 E~+data acquisition and analysis system. The level of serum endotoxin was measured. The level of insulin and insulin antibody in heart were measured by radioimmunoassay. The changes of MDA, MPO and lactic acid in heart were measured by kit. Results: HR decreased obviously in the I group and the I/R group, but the amount increase gradually with the prolongation of reperfusion, there was a statistic significance in I/R2h group, I/R4h group, I/R6h group compared with I/R group(P<0.05), there was no statistic significance compared with CTL(P>0.05), there was no statistic significance in 654-2 group compared with CTL and I/R4h group(P >0.05). The decrease of LVSP has statistic significance in I group and I/R group compared with CTL(P<0.05), the level of LVSP rise to normal in I/R2h group, the decrease of LVSP has statistic significance in I/R4h group and I/R6h group compared with CTL(P<0.05), there was a statistic significance in 654-2 group compared with CTL and I/R4h group(P<0.05). The increase of LVEDP has statistic significance in I/R4h group compared with I group(P<0.05), there was a statistic significance between I/R6h group and the other groups (P<0.05), the decrease of LVEDP has statistic significance in 654-2 group compared with CTL and I/R4h group (P<0.05). Although the level of +dp/dtmax fluctuated in the different group, the decrease of +dp/dtmax has statistic significance in I/R6h group compared with CTL, I group, I/R group and I/R2h group(P< 0.05), there was a statistic significance in 654-2 group compared with CTL and I/R4h group(P<0.05). The rising of-dp/dtmax has statistic significance in I/R group and I/R6h group compared with CTL(P<0.05), there was a statistic significance in 654-2 group compared with CTL and I/R4h group (P<0.05). The increase of endotoxin has obviously statistic significance in CTL compared with the other groups (P<0.05), the level of endotoxin reach to peak in I group and I/R group, the amount decrease gradually with the prolongation of reperfusion, but still higher than CTL(P<0.05), there was a statistic significance in 654-2 group compared with CTL and I/R4h group(P<0.05). From I group, the increase of MDA in cardiac organization has statistic significance in CTL compared with the other groups(P<0.05), there was a statistic significance in I/R2h group, I/R4 group, I/R6h group compared with I group and I/R group(P<0.05), there was a statistic significance in 654-2 group compared with CTL and I/R4h group(P<0.05). The level of MPO obviously increased in every reperfusion group, there was a statistic significance compared with CTL and I group(P<0.05), but there was no statistic significance among them(P>0.05), there was a statistic significance in 654-2 group compared with CTL and I/R4h group(P<0.05). The change of lactic acid is that the rising of lactic acid has statistic significance in I/R2h group, I/R4h group, I/R6h group compared with CTL, I group, I/R group(P<0.05), there was no statistic significance in 654-2 group compared with CTL(P>0.05), but the decrease of lactic acid in 654-2 group has a statistic significance compared with I/R4h group(P<0.05). The decrease of insulin in cardiac organization was statistic significance in I/R group compared with I group(P<0.05), however, the level of insulin increased obviously in I/R2h group, there was a statistic significance compared with I/R group(P<0.05), there was a statistic significance in I/R4h group and I/R6h group compared with CTL and I group and I/R2h group(P<0.05), there was no statistic significance in 654-2 group compared with CTL (P>0.05), but there was a statistic significance compared with I/R4h group(P<0.05). The change of insulin antibody is that there was no statistic significance among every group(P > 0.05). Conclusion: During the process of liver I/R injury, endotoxin was absorbed from intestine and reducement of deintoxication of hepatic led to endotoxemia which plays one of the roles in the changes of the cardiac function, metabolism and structure. 654-2 plays a role in protecting the heart during ischemia reperfusion injury.更多还原