【作者】 杨磊；

【导师】 曹农；

【作者基本信息】 兰州大学 ， 普通外科， 2011， 硕士

【摘要】 目的探讨精氨酸加压素(arginine vasopressin,AVP)通过中枢及外周对脓毒症大鼠动脉压力反射(arterial baroreflex,ABR)的影响,及精氨酸加压素(AVP)对脓毒症大鼠的肝、肾的保护作用。为进一步探讨AVP在脓毒症发病中的作用机制提供实验基础。方法1.雄性SD大鼠通过盲肠结扎穿刺术(CLP)制作脓毒症大鼠模型；2.以假手术组(n=4)为对照,部分CLP大鼠(n=18)术后4h、8h、12h测ABR功能；3.通过免疫组化测定CLP后4h、8h、12h大鼠下丘脑室上核(SON)和室旁核(PVN)AVP阳性神经元的表达；4.部分大鼠CLP术后8小时通过侧脑室注射AVP的方式中枢补充AVP(n=6)侧脑室注射人工脑脊液(aCSF,n=4)作为对照组,另一部分大鼠CLP术后6小时通过静脉持续泵入AVP(n=6),经脉泵入生理盐水(n=4)作为对照组,分别于停药后5分钟和30分钟各测一次ABR功能；5.实验结束后通过颈总动脉插管抽取每只大鼠的血液约5ml,离心取血清,全自动生化仪检测血清ALT、AST、ALP、BUN及Cr。结果1.CLP术后随时间推移大鼠ABR功能逐渐降低；CLP术后大鼠下丘脑室上核(SON)和室旁核(PVN)AVP阳性细胞的表达随时间推移逐渐减少；2.与对照组相比CLP术后8小时侧脑室注射AVP (50ng)后可明显升高脓毒症大鼠的血压(BP),改善动脉压力反射(ABR),加快心率(HR); CLP术后6小时静脉持续泵入AVP (2 ng/kg/h) 2小时与静脉泵入生理盐水2小时组相比,压力敏感性反射显著改善；3.CLP术后4h后大鼠血浆ALT、AST、ALP、BUN及Cr开始升高,CLP术后8h有统计学意义,后ALT、AST、ALP、BUN及Cr逐渐升高,CLP术后6小时静脉持续泵入AVP[(2 ng/(kg·h)]2小时与静脉泵入生理盐水2小时组相比大鼠血浆ALT、AST、ALP、BUN及Cr明显降低；但CLP术后8h侧脑室给予AVP后大鼠血浆ALT、AST、ALP、BUN及Cr与对照组比较明显升高。结论1.脓毒症发病过程中中枢AVP的减少导致ABR功能降低,中枢AVP的减少可能是脓毒症早期向脓毒症休克期进展的关键因素；2.脓毒症早期给予外源性的AVP可改善脓毒症大鼠的ABR,延缓脓毒症大鼠向脓毒症休克期的进展；3.脓毒症大鼠肝肾功能受损可能与血浆AVP水平有关,早期静脉给予AVP可改善肝肾功能,具有器官保护作用。更多还原

【Abstract】 ObjectiveTo investigate the effects of central and peripheral supplement of arginine vasopressin (AVP) on arterial baroreflex (ABR) function in sepsis rats, and explore the effect of arginine vasopressin (AVP) on protecting organic function in septic rats.Methods1. The sepsis model was induced in Male SD rats by cecal ligation puncture (CLP).2. The ABR functions were determined and AVP-like immunoreactivities were detected by immunohistochemical method in supraoptic and paraventricular nucleus of CLP (n=18) or sham operation (n=4) rats after 4 h,8 h or 12 h of CLP.3. In another 20 CLP rats, AVP was supplemented by continuous intravenous infusion or intracerebroventricular injection before ABR functions were determined.4. After injection, all rats were killed, and leaving each animal’s blood, then ALT,AST,ALP,BUN and Cr to be determinated.Results1. Sepsis produces a gradual decrease in ABR function, as well as a gradual reduction in AVP expression ratio in supraoptic and paraventricular nucleus.2. Compared with sham operation group, inject AVP(50 ng) into lateral ventricles(LV) 8 hours after CLP caused an increase in ABR, MAP and HR. Continuous infusion of AVP at a rate of 2 ng/kg/h 6 hours after CLP generated a profound increase in MAP and ABR, as well as a decrease in HR.3. Sepsis produce a gradual increase in ALT,AST,ALP,BUN and Cr from 4 h after CLP, and more significantly after. Compared with sham operation group,continuous infusion of AVP at a rate of 2 ng/kg/h 6 hours after CLP generated a profound decrease in ALT,AST,ALP,BUN and Cr. But inject AVP(50 ng) into lateral ventricles(LV) 8 hours after CLP caused an increase in ALT,AST,ALP,BUN and Cr.Conclusion1. In sepsis, the reduction of AVP expression ratio in supraoptic and paraventricular nucleus induces a decrease in ABR, and that this may contribute to promote sepsis to septic shock..2. Continuous infusion of AVP in the initial phase of sepsis can facilitate ABR function and prolong the time from sepsis to septic shock.3. We assessed the function of liver and renal in relation to plasma vasopressin levels in the rats with endotoxemia. Continuous infusion of AVP at the initial phase of septic shock can protect some organs’ function.更多还原