用活大肠杆菌建立脓毒性休克大鼠模型及对去甲肾上腺素的反应

Q4 Pharmacology, Toxicology and Pharmaceutics Indian journal of physiology and pharmacology Pub Date : 2022-08-10 DOI:10.25259/ijpp_449_2021
Sajo Thomas, Soosai A. Manickam, F. A. Mukadam, A. V, S. Subramani
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引用次数: 0

摘要

常见的感染性休克动物模型包括注射内毒素(细菌脂多糖)。其他诱导败血症的方法通常耗时且需要长期监测设施。此外,使用不同菌株的个体模型可以加深我们对脓毒症病理生理学的理解。因此,我们的目标是利用活的大肠杆菌菌株建立急性功能性脓毒性休克Wistar大鼠模型,然后给药去甲肾上腺素(一种已知的拟交感神经药物),研究反应是否符合预期。随机分为三组(第一组-大肠杆菌,n=7;第2组-大肠杆菌,随后给予去甲肾上腺素(n = 7),第3组-对照组(n = 4),给予生理盐水注射,麻醉Wistar大鼠,颈动脉导管记录动脉内压。活大肠杆菌悬浮在生理盐水(5麦克法兰浓度;剂量为650 uL/100 g体重),经尾静脉注射致脓毒症。当平均动脉压降至注射大肠杆菌前的50%时,第2组注射去甲肾上腺素。脓毒性休克发生的平均时间(t1, n = 14)约为1.94±0.97 h, 7只大鼠中有6只(1组)在未干预的情况下于60 min内死亡。第2组在低血压后加入去甲肾上腺素可使大鼠死亡时间明显延长约170 min。本研究采用大肠杆菌建立的大鼠感染性休克模型是研究感染性休克各方面的急性、稳定、功能性模型。如预期的那样,去甲肾上腺素延长了感染性休克动物的寿命。未来的研究使用其他常见的败血症药物在诊所可以进行类似。
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A rat model of septic shock using live Escherichia coli and response to Noradrenaline
Popular animal models of septic shock involve injections of endotoxin (bacterial lipopolysaccharide). Other methods that induce sepsis are often time-consuming and require long-term monitoring facilities. Further, individual models using different bacterial strains can deepen our understanding of sepsis pathophysiology. Hence, our objective was to develop an acute and functional Wistar rat model of septic shock using live strains of Escherichia coli and then administer Noradrenaline, a known sympathomimetic drug, to study if the response is along expected lines. After random allocation to one of three groups (Group 1 – E. coli alone, n=7; Group 2 – E. coli followed by Noradrenaline, n = 7 and Group 3 – control (n = 4), which received saline injections), Wistar rats were anesthetised and intra-arterial pressure was recorded from carotid artery catheter. Live E. coli suspended in normal saline (5 Mcfarland concentration; dose – 650 uL/100 g body weight) was injected through the tail vein to induce sepsis. When mean arterial pressure dropped to 50% of its value before E. coli injection, Noradrenaline was injected in Group 2. The average time (t1, n = 14) for the septic shock to set in was about 1.94 ± 0.97 h. Six out of seven rats (Group 1) died within 60 min without intervention. The addition of Noradrenaline after hypotension in Group 2 prolonged the time to death significantly by about 170 min. The rat septic shock model using E. coli described in the study is an acute, stable, and functional model to study various aspects of septic shock. Administration of Noradrenaline prolonged the animal’s life in septic shock as expected. Future studies using other common sepsis agents encountered in clinics can be undertaken similarly.
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来源期刊
Indian journal of physiology and pharmacology
Indian journal of physiology and pharmacology Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
0.50
自引率
0.00%
发文量
35
期刊介绍: Indian Journal of Physiology and Pharmacology (IJPP) welcomes original manuscripts based upon research in physiological, pharmacological and allied sciences from any part of the world.
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