目的 觀察COPD 大鼠氣道平滑肌細(xì)胞( ASMCs) 的鈣激活性鉀通道( KCa ) 的活性變化, 以及11, 12-表氧化二十碳三烯酸( 11, 12-EETs) 對氣道平滑肌細(xì)胞KCa 的作用。方法 40 只雄性SD 大鼠隨機分為正常對照組和COPD 組, 每組20 只。在相對密閉艙內(nèi)吸入紙煙建立COPD 動物模型, 采用急性酶分離法分離大鼠ASMCs, 應(yīng)用膜片鉗技術(shù), 分離出KCa 電流, 測定KCa 開放概率( Po) 、平均開放時間( To) 和平均關(guān)閉時間( Tc) 。比較COPD 組和正常對照組KCa上述活性指標(biāo)的變化, 以及應(yīng)用3 μmol / L 的11, 12-EETs 對COPD 組ASMCs 細(xì)胞進(jìn)行灌流后KCa活性的變化。結(jié)果 與正常對照組比較, COPD 組ASMCs 的KCa 通道Po 明顯降低( 0. 084 ±0. 028 比0. 198 ±0. 029, P lt;0. 01) , To 顯著縮短[ ( 0.732 ±0. 058) ms 比( 1. 648 ±0. 152) ms, P lt; 0. 01] , Tc 顯著延長[ ( 12. 259 ±2. 612) ms 比( 6. 753 ±1. 237) ms, P lt; 0. 01] 。而用11, 12-EETs 灌流ASMCs 細(xì)胞后可明顯激活KCa活性, Po 增加( 0.227 ±0. 059 比0. 084 ±0. 028, P lt; 0. 01) , To 延長[ ( 2.068 ±0. 064) ms 比( 0. 732 ±0. 058) ms, P lt;0. 01] , Tc 縮短[ ( 4. 273 ±0. 978) ms 比( 12. 259 ±2. 612) ms, P lt; 0. 01] 。結(jié)論 COPD大鼠ASMCs 細(xì)胞KCa通道活性降低可能在COPD 發(fā)病機制中起著一定作用, 11, 12-EETs 可以直接激活COPD大鼠ASMCs 細(xì)胞KCa活性, 提高膜電位穩(wěn)定性, 從而松弛COPD大鼠氣道平滑肌。
引用本文： 肖欣榮,彭華生,徐賢華,胡猛,閆翔,張汝,孫梅芹. 11, 12-表氧化二十碳三烯酸對COPD 大鼠氣道平滑肌細(xì)胞鈣激活性鉀通道的作用. 中國呼吸與危重監(jiān)護雜志, 2009, 09(2): 122-126. doi: 復(fù)制
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| 3. | 肖欣榮, 陳文彬, 程德云, 等. 脫氫表雄甾酮對缺氧慢性大鼠肺動脈平滑肌細(xì)胞鈣激活性鉀通道的作用. 中華結(jié)核和呼吸雜志, 2004, 27: 41-45. |
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| 5. | Wellman GC, Bonev AD, Nelson MT, et al. Gender differences in coronary artery diameter involve estrogen, nitric oxide and Ca2 +dependent K + channels. Circ Res, 1996, 79: 1024-1030. |
| 6. | Bonnet S, Savineau JP, Barillot W, et al. Role of Ca( 2 + ) -sensitive K( + ) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases. Cardiovas Res, 2003, 60 :326-336. |
| 7. | Capdevila J, Chacos N, Werringloer J, et al. Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc Natl Acad Sci USA, 1981, 78: 5362-5366. |
| 8. | Fisslthaler B, Popp R, Kiss L, et al. Cytochrume P-450 2C is an EDHF synthase in coronary arteries. Nature, 1999, 401: 493-497. |
| 9. | Knot HJ, Standen NB, Nelson MT. Ryanodine receptors regulate arterial diameter and wall [ Ca2 + ] in cerebral arteries of rat via Ca2+ -dependent K+ channels. J Physiol, 1998, 508: 211-221. |
| 10. | Brayden JE, Nelson MT. Regulation of arterial tone by activation of calcium-dependent potassium channels. Science, 1992 , 256 : 532 -535. |
- 1. Marc D, Dany S, Sophie B, et al. Epoxyeicosatrienoic acids relax airway smooth muscles and directly activate reconstituted KCa channels. AmJ Physiol Lung Cell Mol Physiol, 1998, 275: 423-431.
- 2. 王慧, 程德云, 關(guān)鍵, 等. 單核細(xì)胞趨化蛋白-1 與COPD 大鼠氣道炎癥的研究. 四川大學(xué)學(xué)報( 醫(yī)學(xué)版) , 2004, 35: 634-637.
- 3. 肖欣榮, 陳文彬, 程德云, 等. 脫氫表雄甾酮對缺氧慢性大鼠肺動脈平滑肌細(xì)胞鈣激活性鉀通道的作用. 中華結(jié)核和呼吸雜志, 2004, 27: 41-45.
- 4. Peng W, Hoidal JR, Karwande SV, et al. Effect of chronic hypoxia on K + channels: regulation in human pulmonary vascular smooth muscle cells. Am J Physiol, 1997, 272: C1271-C1278.
- 5. Wellman GC, Bonev AD, Nelson MT, et al. Gender differences in coronary artery diameter involve estrogen, nitric oxide and Ca2 +dependent K + channels. Circ Res, 1996, 79: 1024-1030.
- 6. Bonnet S, Savineau JP, Barillot W, et al. Role of Ca( 2 + ) -sensitive K( + ) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases. Cardiovas Res, 2003, 60 :326-336.
- 7. Capdevila J, Chacos N, Werringloer J, et al. Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc Natl Acad Sci USA, 1981, 78: 5362-5366.
- 8. Fisslthaler B, Popp R, Kiss L, et al. Cytochrume P-450 2C is an EDHF synthase in coronary arteries. Nature, 1999, 401: 493-497.
- 9. Knot HJ, Standen NB, Nelson MT. Ryanodine receptors regulate arterial diameter and wall [ Ca2 + ] in cerebral arteries of rat via Ca2+ -dependent K+ channels. J Physiol, 1998, 508: 211-221.
- 10. Brayden JE, Nelson MT. Regulation of arterial tone by activation of calcium-dependent potassium channels. Science, 1992 , 256 : 532 -535.