M3受体亚型介导内毒素诱导兔离体肺动脉舒张反应的研究  

Endotoxin Decreases the Relaxation Response to Acetylcholine Mediated by M3 Receptor Subtype in Isolated Rabbit Pulmonary Arteries

作　　者：索良源[1] 于泓波[2] 张锦[3] 

机构地区：[1]中国医科大学肿瘤医院辽宁省肿瘤医院麻醉科,辽宁沈阳110042 [2]沈阳市骨科医院麻醉科,辽宁沈阳110044 [3]中国医科大学附属盛京医院麻醉科,辽宁沈阳110004

出　　处：《中国呼吸与危重监护杂志》2016年第5期506-510,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：沈阳市重点应用基础课题(编号:071021;F14-231-60)

摘　　要：目的 探讨M毒蕈碱受体（muscarinic receptor M）亚型M3对内毒素诱导的肺动脉环张力的调节作用及在内毒素作用下M3受体的变化,以探讨感染性休克肺动脉血管反应性改变的机制。方法 选择健康雄性新西兰大白兔26只,体重2.0-2.5 kg,随机分2组：盐水加达非那新正常组（N组,n=45）,内毒素加达非那新组（L组,n=48）。通过离体血管环技术观察正常及M3受体亚型阻断剂达非那新不同剂量（100、10、1、0.1和0.01μmol/L）分别预孵育后血管对苯肾上腺素（PE1μmol/L）及乙酰胆碱（ACH 1、10和100μmol/L）的张力变化。结果 （1）正常组肺动脉对ACH累计曲线的舒张百分比分别为（0.095±0.034）%,（0.150±0.036）%,（0.445±0.090）%,用内毒素（4μg/m L,4 h）处理后分别为（0.044±0.016）%,（0.093±0.029）%,（0.311±0.028）%。（2）达非那新对不同浓度ACH（1、10和100μmol/L）反应得出的EC50值分别为正常组1.483、2.757和2.958,内毒素组6.015、6.242和6.411。（3）达非那新对不同浓度的ACH（1、10和100μmol/L）反应得出的内在活性a值分别为正常组0.014 6、0.032 3和0.082 5,内毒素组0.012 4、0.024 5和0.055 6。结论 内毒素孵育降低了肺动脉对ACH的舒张反应,M3受体亚型介导了此舒张反应;内毒素减低了M3受体亚型的内在活性。内毒素使M3受体亚型内在活性降低是内毒素作用下肺动脉对ACH舒张反应降低的作用机制之一,也可能是感染性休克时肺动脉高压形成的作用机制之一。Objective To investigate the regulatory roles and changes of M3 receptor subtype in lipopolysaccharide （LPS） -preincubated rabbit pulmonary arteries, and assess the mechanism of altered vascular reactivity in septic shock. Methods Pulmonary arteries with intact endothelium were isolated from 26 male New Zealand white rabbits weighing 2. 0 to 2. 5kg. The isolated pulmonary arteries were randomized into two grouops, including a normal group with normal saline and darifenacin adminstration, and an endotoxin group with LPS-preineubation and darifenacin adminstration. The response of arteries to phenylephrine （100μmol/L） and acetylcholine（ACH） （ 11μmol/L, 10μmol/L, 100μmol/L） were measured in normal and darifenacin-preincubated circumstances. Results The percentages of ralaxation to ACH （1μmol/L, 10μmol/L, 100μ mol/L） were （0.095 ±0.034）% ,（0. 150 ±0.036）% ,and （0.445 ±0.090）% in the normal group, and （ 0. 044 ± 0. 016 ） %, （ 0. 093 ± 0. 029 ） %, （ 0. 311 ± 0. 028 ） % in the endotoxin （ LPS 4μg/mL, 4h） group. After pretreatment with M3 receptor antagonist darifenacin on different concentrations, the EC50 values responding to ACH （ 1 μmol/L, 10μmol/L, 100μmol/L） were 1. 483,2. 757,2. 958 in the normal group, and 6.015,6. 242, 6.411 in the endotoxin group. After pretreatment with M3 receptorantagonist darifenacin on different concentrations, the inherent activity of a value to ACH （1μmol/L, 10μmol/L, 100μmol/L） were 0. 0146,0. 0323,0. 0825 in the normal group,and 0. 0124,0. 0245,0. 0556 in the endotoxin group. Conclusions LPS pre-incubation can reduce the relaxation response to ACH,and M3 receptor subtypes mediated this relaxation response. LPS also reduce the M3 receptor subtype intrinsic activity,which may be one of the mechanisms of decreased relaxation response to ACH in pulmonary arteris after LPS pretreatment, and also one of the mechanisms of pulmonary hypertension in septic shock.

关 键 词：舒张反应 M3受体 内在活性 内毒素休克 内毒素诱导 感染性休克 受体亚型 阻断剂 血管反应性 毒蕈碱受体 

分 类 号：R614[医药卫生—麻醉学]