本文選題：丙泊酚 + 人肺內(nèi)小動脈　； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的丙泊酚因起效快,作用迅速,持續(xù)時間短,消退快常用于麻醉的誘導(dǎo)和維持,成為臨床麻醉應(yīng)用最廣泛的靜脈麻醉藥物。與此同時,丙泊酚對循環(huán)系統(tǒng)的影響受到麻醉工作者廣泛關(guān)注。目前研究已證明,丙泊酚能降低體循環(huán)血管床阻力,引起體動脈呈濃度依賴舒張,然而其對于肺循環(huán)的作用卻存在較大爭議。本研究擬探究丙泊酚對經(jīng)U46619預(yù)收縮的離體人肺內(nèi)小動脈血管張力影響及其機(jī)制。方法1.選取因肺腫瘤行肺葉切除手術(shù)的病人腫瘤周圍正常肺組織作為實驗標(biāo)本,體式顯微鏡下分離人肺內(nèi)小動脈。1.將分離好的人肺內(nèi)小動脈環(huán)隨機(jī)分為內(nèi)皮完整組(n=24)和去內(nèi)皮組(n=24)。每組分別包括:丙泊酚處理組(n=8)②100nmol/L U46619+丙泊酚處理組(n=8)③100nmol/L U46619+丙泊酚+吲哚美辛處理組(n=8)。2.內(nèi)皮完整的血管環(huán):(1)格列本脲10μmol/L+1000μmol/L吲哚美辛+100 nmol/L+U46619+丙泊酚處理組(n=8)(2)BaCl2 10μmol/L+100 μmol/L 吲哚美辛+100 nmol/L U46619+丙泊酚處理組(n=8)(3)TEA+10μmol/L+100 μmol/L吲哚美辛+100 nmol/L U46619+丙泊酚處理組(n=8)(4)60mmol/L高鉀+丙泊酚處理組(n=8)。使用微血管張力測定技術(shù),采用累計加藥法加入丙泊酚(10-300μmol/L),觀察不同濃度丙泊酚對預(yù)收縮的人肺內(nèi)小動脈張力的影響及機(jī)制;3.將制備好的人肺內(nèi)小動脈環(huán)(n=12)置于無鈣高鉀溶液中分為三組,每組(n=4)分別經(jīng)不同濃度異丙酚(0-100μmol/L)孵育后,累計加藥法加入鈣離子,觀察鈣離子引起的收縮反應(yīng);4.分離人離體肺內(nèi)小動脈血管平滑肌細(xì)胞,通過激光共聚焦熒光顯微鏡分析肺動脈血管平滑肌細(xì)胞經(jīng)丙泊酚孵育后加入鈣離子時細(xì)胞內(nèi)鈣離子濃度的變化。結(jié)果1.丙泊酚對于靜息狀態(tài)下肺內(nèi)小動脈張力無明顯作用;2.丙泊酚對U46619預(yù)收縮人離體肺內(nèi)小動脈產(chǎn)生低濃度(10-100μmol/L)收縮高濃度(100-300μmol/L)舒張雙相作用,且去內(nèi)皮組在低濃度產(chǎn)生收縮幅度(Emax=31.19±5.10%)高于內(nèi)皮完整組(Emax=30.44±2.92%),P0.05;3.吲哚美辛可阻斷丙泊酚引起的收縮反應(yīng),引起舒張反應(yīng)最大舒張率內(nèi)皮完整組(Emax=98.72±0.34%)高于去內(nèi)皮組(Emax=94.56±0.53%),P0.05;格列本脲、BaC12、TEA+對丙泊酚引起的舒張效應(yīng)沒有影響4.丙泊酚對60 mmol/L高鉀預(yù)收縮內(nèi)皮完整的人離體肺內(nèi)小動脈產(chǎn)生濃度依賴舒張作用,其最大舒張率Emax=(98.57 ± 1.18)%5.不同濃度異丙酚(0-100μmol/L)孵育后,鈣離子在無鈣高鉀溶液中引起收縮反應(yīng)曲線明顯右移;6.使用fluo-4的Ca2+的熒光成像顯示,異丙酚(10-300 μmol/L)孵育10分鐘,呈濃度依賴性的抑制鈣離子進(jìn)入肺動脈血管平滑肌細(xì)胞,降低細(xì)胞內(nèi)[Ca2+]i。結(jié)論丙泊酚對經(jīng)U46619收縮的人肺內(nèi)小動脈呈低濃度收縮高濃度舒張雙相作用。其收縮作用可能與丙泊酚作用于肺動脈平滑肌COX源性收縮或舒張有關(guān),舒張作用部分由內(nèi)皮細(xì)胞參與,主要與抑制L型VGCC相關(guān)鈣內(nèi)流有關(guān)。
[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 鹵5.10) at low concentration, which was higher than that of endothelium-intact group (30.44 鹵2.922). Indomethacin could block the contraction response induced by propofol, and the maximal diastolic rate was 98.72 鹵0.34 in the intact endothelium group, which was higher than that in the endothelium-free group (94.56 鹵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 鹵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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R614

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