【作者】 唐力；

【导师】 吕国荣； 李伯义；

【作者基本信息】 福建医科大学 ， 内科学， 2009， 博士

【摘要】 目的采用多普勒超声检测胎羊炎症反应综合征(FIRS)血流动力学变化,同时分析各种动力学参数与TNF-α、IL-6之间的相关性。并初步探讨FIRS时胎羊心功能改变可能机理。方法22只晚孕山羊分成3组:1.对照组;2.脐静脉给内毒素(LPS)组;3.羊膜腔内给LPS组。两给LPS组行超声引导下脐静脉穿刺术和羊膜腔穿刺术,注射LPS,并分别于注射LPS前后不同时间点采用多普勒超声心动图检测胎羊各种血流动力学参数,同时取胎羊血检测TNF-α、IL-6含量以及丙二醛(MDA)、心肌肌钙蛋白I(cTnI)含量,评价各种血流动力学参数与TNF-α、IL-6之间的相关性。检测心肌组织Fas mRNA表达水平及心肌细胞核转录因子(NF-κB p65)蛋白含量,免疫组化测量心肌组织胱门蛋白酶3(caspase3)表达。结果1.实验组给LPS后TNF-α、IL-6随时间升高(P＜0.05),与对照组比较差异有统计学意义(P＜0.05)。2.外周血管中脐动脉(UmA)、肾动脉(RA)、静脉导管(DV)搏动指数(PI)均随时间升高(P＜0.05),并且高于对照组(P＜0.05);大脑中动脉(MCA)PI随时间持续下降(P＜0.05),并且低于对照组(P＜0.05)。3.心功能指标中,左心室、右心室(LV、RV)Tei指数随时间升高(P＜0.05),与对照组比较差异有统计学意义(P＜0.05);三尖瓣、二尖瓣(TV、MV)E/A值、(LV、RV)射血分数(EF)先升高,随后持续下降(P＜0.05),与对照组比较差异有统计学意义(P＜0.05)。4.胎羊UmAPI,RAPI,DV PI,(LV、RV)Tei指数,与血TNF-α水平呈正相关(r=0.724,r=0.668,r=0.784,r=0.765,r=0.683,P＜0.01),与血IL-6水平呈正相关(r=0.771,r=0.760,r=0.823,r=0.805,r=0.749,P＜0.01),MCA PI与血TNF-α、IL-6水平呈负相关性(r=-0.727,r=-0.728,P＜0.01)。LV EF、RV EF、TV E/A、MV E/A与血TNF-α水平没有相关性(r=-0.195,r=-0.157,r=-0.204,r=-0.156,P＞0.05),与血IL-6水平也没有相关性(r=-0.157,r=-0.128,r=-0.199,r=-0.228,P＞0.05)。5.实验组给LPS后MDA、cTnI随时间升高(P＜0.05),与对照组比较差异有统计学意义(P＜0.05)。6.实验组给LPS后心肌组织的NF-κB p65蛋白含量增加、Fas mRNA表达上调、caspase3表达增加(P＜0.05),与对照组比较差异有统计学意义(P＜0.05)。结论1.外周血管中DV PI与胎羊血TNF-α、IL-6水平之间的相关性最强;心功能指标中Tei指数与胎羊血TNF-α、IL-6水平之间的相关性最强。因此,DV PI与Tei指数可作为预测FIRS简单而有效的参考指标。2.LPS引发胎羊体内炎症级联反应,多种因素参与其中,导致胎羊发生SIRS,最终能导致多器官功能衰竭(MOF)。3.心肌细胞的凋亡在SIRS胎羊心肌损伤中可能起着重要的作用。更多还原

【Abstract】 Objective To evaluate the changes of hemodynamic during fetal inflammatory response syndrome(FIRS) period by Doppler ultrasound,and assess the corrlation between hemodynamic paratmeters and fetal plasma TNF-αand IL-6 concentration, and explore its possible mechanism in fetal cardiac function.Methods 22 near-term pregnant sheep were used in this study,Uuder ultrasound guidance,10 animals were performed with LPS-cordocentesis,7 animals were performed with LPS-amniocentesis and another 5 animals as a control group.In experiment groups animal,LPS was injected into the umbilical cord vein(10μg/kg of fetal body weight) and amniotic cavity(200μg/kg of maternal body weight) at 120(range 116-130) days gestation(term=145 days ),respectively.Doppler echocardiography were performed at different time during LPS administration.Fetal umbilical cord blood samples were collected and measured for TNF-α,IL-6,MDA and cTnI.The correlation coefficient was calculated to established the relationship between the TNF-α,IL-6 concentation and Doppler scanning values.The mRNA of Fas and protein of nuclear factor-K B p65(NF-κB p65 ) and caspase3 of fetal myocardium were examined with immunohistochemistry.Results 1.After LPS administration,the fetal plasma TNF-α,IL-6 level significantly increased with time(P<0.05),and still significantly increased as compared with the control animals(P<0.05).2.In the peripheral vessels,the fetal umbilical artery (UmA),renal artery(RA),ductus venous(DV) waveform pulsatility index(PI) values significantly increased with time(P<0.05),and still significantly increased as compared with the control animals(P<0.05).However,the fetal middle cerebral artery(MCA) PI values significantly reduced with time(P<0.05),and still significantly reduced as compared with the control animals(P<0.05).3.In the cardiac function values,left and right ventricle(LV,RV) Tei indices significantly increased with time(P<0.05),and still significantly increased as compared with the control animals (P<0.05),however,LV ejection fraction(EF),RV EF,tricuspid valve(TV) E/A ratio and mitral valve(MV) E/A ratio significantly increased and thus reduced(P<0.05),and still significantly different as compared with the control animals(P<0.05).4.There were significantly positive correlation between UmA PI,RA PI,DV PI,LV Tei index, RV Tei index and TNF-α(r=0.724,r=0.668,r=0.784,r=0.765,r=0.683,P<0.01) and IL-6(r=0.771,r=0.760,r=0.823,r=0.805,r=0.749,P<0.01 ).There were significantly negative correlation between MCA PI and TNF-α,IL-6(r=-0.727, r=-0.728,P<0.01 ).And there were no correlation between LV EF,RV EF,TV E/A ratio,MV E/A ratio and TNF-α(r=-0.195,r=-0.157,r=-0.204,r=-0.156, P>0.05) and IL-6(r=-0.157,r=-0.128,r=-0.199,r=-0.228,P >0.05).5.After LPS administration,the fetal plasma MDA,cTnI level significantly increased with time(P<0.05),and still significantly increased as compared with the control animals (P<0.05).6.FIRS could upregulating the express of Fas mRNA,enhancing the protein quantity of NF-κB p65,increasing the express of caspase3 in fetal myocardium(P<0.05),and still significantly different as compared with the control animals(P<0.05).Conclusions 1.Mostly Doppler parameters were significantly associated with TNF-αand IL-6 concentration.DV PI exhibits the strongest relationship in peripheral vessels,and Tei index exhibits the strongest relationship in cardiac function values,respectively.Therefore,DV PI and Tei index might be an useful quantitative parameters for assessing FIRS.2.Apotosis of myocardial cell might be associated with cardiac dysfunction.更多还原