丙泊酚对离体人肺内小动脉张力的作用及机制

发布时间：2018-05-09 07:05

本文选题：丙泊酚 + 人肺内小动脉　；参考：《南方医科大学》2017年硕士论文

【摘要】：目的丙泊酚因起效快,作用迅速,持续时间短,消退快常用于麻醉的诱导和维持,成为临床麻醉应用最广泛的静脉麻醉药物。与此同时,丙泊酚对循环系统的影响受到麻醉工作者广泛关注。目前研究已证明,丙泊酚能降低体循环血管床阻力,引起体动脉呈浓度依赖舒张,然而其对于肺循环的作用却存在较大争议。本研究拟探究丙泊酚对经U46619预收缩的离体人肺内小动脉血管张力影响及其机制。方法1.选取因肺肿瘤行肺叶切除手术的病人肿瘤周围正常肺组织作为实验标本,体式显微镜下分离人肺内小动脉。1.将分离好的人肺内小动脉环随机分为内皮完整组(n=24)和去内皮组(n=24)。每组分别包括:丙泊酚处理组(n=8)②100nmol/L U46619+丙泊酚处理组(n=8)③100nmol/L U46619+丙泊酚+吲哚美辛处理组(n=8)。2.内皮完整的血管环:(1)格列本脲10μmol/L+1000μmol/L吲哚美辛+100 nmol/L+U46619+丙泊酚处理组(n=8)(2)BaCl2 10μmol/L+100 μmol/L 吲哚美辛+100 nmol/L U46619+丙泊酚处理组(n=8)(3)TEA+10μmol/L+100 μmol/L吲哚美辛+100 nmol/L U46619+丙泊酚处理组(n=8)(4)60mmol/L高钾+丙泊酚处理组(n=8)。使用微血管张力测定技术,采用累计加药法加入丙泊酚(10-300μmol/L),观察不同浓度丙泊酚对预收缩的人肺内小动脉张力的影响及机制;3.将制备好的人肺内小动脉环(n=12)置于无钙高钾溶液中分为三组,每组(n=4)分别经不同浓度异丙酚(0-100μmol/L)孵育后,累计加药法加入钙离子,观察钙离子引起的收缩反应;4.分离人离体肺内小动脉血管平滑肌细胞,通过激光共聚焦荧光显微镜分析肺动脉血管平滑肌细胞经丙泊酚孵育后加入钙离子时细胞内钙离子浓度的变化。结果1.丙泊酚对于静息状态下肺内小动脉张力无明显作用;2.丙泊酚对U46619预收缩人离体肺内小动脉产生低浓度(10-100μmol/L)收缩高浓度(100-300μmol/L)舒张双相作用,且去内皮组在低浓度产生收缩幅度(Emax=31.19±5.10%)高于内皮完整组(Emax=30.44±2.92%),P0.05;3.吲哚美辛可阻断丙泊酚引起的收缩反应,引起舒张反应最大舒张率内皮完整组(Emax=98.72±0.34%)高于去内皮组(Emax=94.56±0.53%),P0.05;格列本脲、BaC12、TEA+对丙泊酚引起的舒张效应没有影响4.丙泊酚对60 mmol/L高钾预收缩内皮完整的人离体肺内小动脉产生浓度依赖舒张作用,其最大舒张率Emax=(98.57 ± 1.18)%5.不同浓度异丙酚(0-100μmol/L)孵育后,钙离子在无钙高钾溶液中引起收缩反应曲线明显右移;6.使用fluo-4的Ca2+的荧光成像显示,异丙酚(10-300 μmol/L)孵育10分钟,呈浓度依赖性的抑制钙离子进入肺动脉血管平滑肌细胞,降低细胞内[Ca2+]i。结论丙泊酚对经U46619收缩的人肺内小动脉呈低浓度收缩高浓度舒张双相作用。其收缩作用可能与丙泊酚作用于肺动脉平滑肌COX源性收缩或舒张有关,舒张作用部分由内皮细胞参与,主要与抑制L型VGCC相关钙内流有关。
[Abstract]:Objective propofol is the most widely used intravenous anesthetic in clinical anesthesia because of its quick effect, quick action, short duration and fast extinction. At the same time, the influence of propofol on the circulatory system has been widely concerned by anesthesiologists. It has been proved that propofol can reduce the flow resistance of systemic circulation and induce concentration-dependent vasodilation. However, the effect of propofol on pulmonary circulation is controversial. The aim of this study was to investigate the effect of propofol on vascular tension of isolated human pulmonary arterioles via U46619 and its mechanism. Method 1. The normal lung tissue around the tumor of patients undergoing lobectomy for lung tumor was selected as the experimental specimen. The arterioles of human lung were separated under the posture microscope. The isolated human pulmonary arterioles were randomly divided into two groups: the intact endothelium group and the endothelium-free group. Each group included: propofol treatment group (n = 8) 2100nmol / L U46619 propofol treatment group (n = 3100nmol / L U46619) and propofol indolomethacin treatment group (n = 8100nmol / L). Vascular ring: 1) glibenclamide 10 渭 mol/L 1000 渭 mol/L indomethacin 100 nmol/L U46619 propofol treatment group (n = 8) BaCl 2 10 渭 mol/L 100 渭 mol/L indomethacin 100 渭 mol/L nmol/L U46619 propofol treatment group (n = 8) 3TEA 10 渭 mol/L 10 渭 mol/L 100 渭 mol/L indomethacin 100 nmol/L U46619 propofol group. The effect of propofol at 10 ~ 300 渭 mol 路L ~ (-1) on the tension of precontracted human pulmonary arterioles and its mechanism were observed by microvascular tension measurement and cumulative addition of propofol (10-300 渭 mol 路L ~ (-1) 路L ~ (-1)). The prepared human pulmonary arterioles were divided into three groups. Each group was incubated with different concentrations of propofol (0-100 渭 mol / L). The calcium ion was added into the cumulative dosing method to observe the contractile response induced by Ca ~ (2 +). Human pulmonary arteriole vascular smooth muscle cells were isolated. The changes of intracellular calcium concentration in pulmonary artery smooth muscle cells treated with propofol were analyzed by confocal fluorescence microscopy. Result 1. Propofol has no obvious effect on pulmonary arteriole tension in resting state. Propofol had a low concentration of 10-100 渭 mol / L (10 ~ 100 渭 mol / L) contraction and 100 ~ 300 渭 mol 路L ~ (-1) diastolic biphasic effect on U46619 precontracted human pulmonary arterioles, and the contraction amplitude of endothelium-free group was 31.19 卤5.10) at low concentration, which was higher than that of endothelium-intact group (30.44 卤2.922). Indomethacin could block the contraction response induced by propofol, and the maximal diastolic rate was 98.72 卤0.34 in the intact endothelium group, which was higher than that in the endothelium-free group (94.56 卤0.53 P 0.05), but the relaxation effect of propofol was not affected by BAC 12TEA. Propofol had a concentration-dependent relaxation effect on the isolated pulmonary arterioles with 60 mmol/L hyperkalemic precontracted endothelium, and its maximal relaxation rate was Emax=(98.57 卤1.18 ~ 5. After different concentrations of propofol (0-100 渭 mol / L) were incubated, the contraction response curve of calcium ion in the solution without calcium and potassium was obviously shifted to the right by 6%. Fluorescence imaging of Ca2 from fluo-4 showed that propofol (10-300 渭 mol / L) was incubated for 10 min and inhibited calcium ions entering pulmonary vascular smooth muscle cells in a concentration-dependent manner, which decreased [Ca2] I in the cells. Conclusion propofol has a low concentration contraction and high concentration diastolic biphasic effect on human pulmonary arterioles contracted by U46619. The contractile effect of propofol may be related to the contraction or relaxation of pulmonary artery smooth muscle COX induced by propofol, which is partly mediated by endothelial cells and mainly related to the inhibition of L-type VGCC related calcium influx.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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