血清C5a在尿源性脓毒血症中的变化及其阻断对感染性休克的影响

发布时间：2018-01-16 02:21

  本文关键词：血清C5a在尿源性脓毒血症中的变化及其阻断对感染性休克的影响　出处：《浙江大学》2017年硕士论文　论文类型：学位论文

  更多相关文章： 腔内碎石术 尿源性脓毒血症 感染性休克 C5a PMX-53 动物模型

【摘要】：目的:尿源性脓毒血症是腔内碎石术后的严重并发症之一,早期诊断和治疗对改善预后非常重要。我们通过建立肾盂内高压伴感染的动物模型,研究尿源性脓毒血症的发展过程中血清补体成分C5a的变化,分析C5a对感染性休克的早期预警价值,探究早期用PMX-53阻断C5a与其受体的结合能否改善感染性休克的预后。方法:首先,将40只雌性新西兰兔随机分为A1、A2、A3及A4四组,向各组兔的肾盂内注入等量生理盐水或不同浓度梯度的标准大肠杆菌溶液,分别监测术前、术后的平均动脉压和血清C5a浓度,以探索肾盂内高压伴感染致急性感染性休克的标准模型浓度。其后,将另40只新西兰兔随机分为B、C、D1及D2四组。对B组,肾盂内注入生理盐水,对C、D1、D2组,肾盂内注入致感染性休克浓度的标准大肠杆菌溶液;术后,对B、C组,在术后1小时静脉注射生理盐水,对D1、D2组注射等量但不同浓度的PMX-5生理盐水溶液,监测实验兔的平均动脉压、血清C5a的浓度和存活时间。结果:肾盂内注射生理盐水组的实验兔术后8小时内平均动脉压较基础动脉压无明显下降。随着注入细菌浓度的升高和术后时间的延长,各注射大肠杆菌组的实验兔术后平均动脉压呈现下降趋势,其中A4组在术后6小时的血压较基础血压的下降有统计学显著性。因此选择A4组所用大肠杆菌浓度作为新西兰兔尿源性休克的标准模型浓度。生理盐水组在术后8小时内血清C5a浓度较术前相比无明显差异,各注射大肠杆菌组在术后8小时内血清C5a浓度呈逐渐升高趋势,且随着大肠杆菌溶液浓度的升高,血清C5a升高的幅度增大。其中,A3组与A4组,与术前相比术后6小时血清C5a、8小时血清C5a均显著性升高。B组术后血压无明显下降(除外麻醉影响),术后24h存活;血清C5a浓度较术前相比无明显差异。C组在术后8.5±0.7小时出现休克,11.3±1.1小时死亡;术后8小时内血清C5a浓度呈逐渐升高趋势。D1、D2组在术后出现休克及死亡时间均晚于C组;术后C5a升高幅度小于C组。结论:该动物模型研究表明血清C5a升高程度与感染程度密切相关,监测术后血清C5a的浓度有助于判断术后脓毒血症的发生及严重程度。早期用PMX-53阻断C5a与其受体C5aR的结合可以延缓术后的感染进程,从而推迟感染性休克的发生。通过优化PMX-53的用量及给药时间,有可能进一步控制感染的进展,甚至可能避免尿源性感染性休克的发生,但这需要进一步的实验验证。
[Abstract]:Objective: urine derived sepsis is one of serious complications after endoscopic lithotripsy, early diagnosis and treatment is very important for improving the prognosis. We through the establishment of animal model of hypertension and renal pelvic infection, changes of serum complement C5a development process research of urosepsis in the analysis of C5a for the early warning value of septic shock the inquiry, early PMX-53 blocking the binding of C5a to its receptors can improve the prognosis of septic shock. Methods: first, 40 female New Zealand rabbits were randomly divided into A1, A2, A3 and A4 four groups, injected into the standard Escherichia coli solution saline or different concentration gradient to rabbit renal pelvis, respectively. Monitoring the preoperative, postoperative mean arterial pressure and serum concentration of C5a, to explore the renal pelvis with high concentration of standard model of infection caused by acute septic shock. Later, the other 40 New Zealand rabbits were randomly divided into B, C D1, and D2 four groups. In group B, intrapelvic injection of saline, C, D1, D2 group, the renal pelvis into standard E. coli solution induced septic shock concentration; after the operation, the B, C group, 1 hours after intravenous injection of saline, D1 group, D2 injection but with different PMX-5 saline solution concentration, mean arterial pressure monitoring in rabbits, the concentration of serum C5a and survival time. Results: the intrapelvic injection of saline group rabbits after 8 hours compared with the mean arterial pressure of arterial pressure decreased significantly. With increasing injection of bacteria concentration and time after operation and the injection of Escherichia coli group in rabbits after operation the mean arterial pressure decreased, the A4 group 6 hours after the blood pressure is the basis of blood pressure was statistically significant. So the choice of group A4 with the concentration of E. coli as the concentration of New Zealand rabbits urogenic shock in the standard model. The saline group in serum within 8 hours postoperatively compared with the preoperative C5a concentration showed no significant difference, the injection of Escherichia coli group. The serum C5a concentration in 8 hours after operation gradually increased, and increased with the increasing concentration of Escherichia coli solution, elevated serum C5a increased. Among them, A3 group and A4 group, compared with 6 hours after surgery and preoperative serum C5a, serum C5a 8 hours were significantly increased after operation in.B group decreased significantly (except blood pressure without anesthesia), survival after 24h; the concentration of serum C5a compared with preoperative.C group showed no significant difference in postoperative 8.5 - 0.7 hours to shock, 11.3 - 1.1 hours of death; the serum C5a concentration increased with.D1 within 8 hours after operation, group D2 shock and death time were later than in the C group after surgery; postoperative C5a was significantly less than that of C group. Conclusion: the study showed that the animal model is closely related to the increased serum C5a level and the degree of infection, monitoring of postoperative serum C The concentration of 5A is helpful in judging the postoperative sepsis incidence and severity. Early PMX-53 blocking C5a binding to its receptor C5aR can delay the progress of infection after surgery, which delayed septic shock occurs. Through the optimization of PMX-53 dosage and administration time, may further control the progression of the infection, and may even avoid urine and septic shock occurred, but this needs further experimental verification.

【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R459.7

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