目的 探討脂聯(lián)素對(duì)氣道平滑肌細(xì)胞( AMSCs) 增殖的影響及相關(guān)機(jī)制的研究。方法 體外培養(yǎng)大鼠氣道平滑肌細(xì)胞株; RT-PCR 法檢測(cè)ASMCs 脂聯(lián)素受體的表達(dá); 不同濃度的脂聯(lián)素( 5、10、20、40 及80 μg/mL) 作用于體外培養(yǎng)的大鼠ASMCs, 孵育不同時(shí)間, MTT 法檢測(cè)吸光值, 計(jì)算細(xì)胞抑制率; 不同濃度脂聯(lián)素( 5、10、20 及40 μg/mL) 作用于氣道平滑肌細(xì)胞48 h 后提取蛋白,Western blot 法檢測(cè)一磷酸腺苷活化蛋白激酶( AMPK) 及磷酸化一磷酸腺苷活化蛋白激酶( pho-AMPK) 的表達(dá)。結(jié)果 5 ~80 μg/mL 脂聯(lián)素在不同時(shí)間( 1、12、24、48 及72 h) 明顯抑制ASMCs 增殖, 并存在濃度依賴性( r =0. 324, P lt;0. 01) 和時(shí)間依賴性( r =0. 607, P lt;0. 01) ; Western blot 法檢測(cè)顯示空白對(duì)照組無(wú)pho-AMPK表達(dá), 干預(yù)組隨著脂聯(lián)素濃度的升高AMPK 的活性增強(qiáng)( r =0. 907, P lt;0. 01) , pho-AMPK/AMPK 比值分別為( 27. 66 ±1. 03) %、( 31.91 ±0. 86) % 、( 75. 52 ±2. 67) % 和( 84. 50 ±1. 05) %, 差異有統(tǒng)計(jì)學(xué)意義( P lt;0. 05) 。結(jié)論 脂聯(lián)素可能通過(guò)激活A(yù)MPK來(lái)抑制體外培養(yǎng)的ASMC 增殖。
引用本文: 郭茂清,朱述陽(yáng). 脂聯(lián)素對(duì)氣道平滑肌細(xì)胞增殖作用及一磷酸腺苷活化蛋白激酶活性的影響. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(3): 264-267. doi: 復(fù)制
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13. | Nagata D, Takeda R, Sata M, et al. AMP-activated protein kinase inhibits angiotensin II-stimulated vascular smooth muscle cell proliferation. Circulation, 2004, 110 : 444-451 . |
14. | Ratnovsky A, Mellema M, An SS, et al. Airway smooth muscle proliferation and mechanics: effects of AMP kinase agonists. Mol Cell Biomech, 2007 , 4: 143-157. |
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- 1. Woodruff PG, Dolganov GM, Ferrando RE, et al. Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression. Am J Respir Crit Care Med, 2004 , 169 :1001-1006.
- 2. 蔡紹曦, 趙海金. 氣道重塑成為哮喘新的治療靶點(diǎn)還有多遠(yuǎn)?中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2006, 5: 404 -407.
- 3. Taylor B, Mannino D, Brown C, et al. Body mass index and asthma severity in the National Asthma Survey. Thorax, 2008, 63: 14 -20 .
- 4. Shore SA. Obesity and asthma: implications for treatment. Curr Opin PulmMed, 2007 , 13 : 56-62.
- 5. Ouchi N, Kihara S, Funahashi T, et al. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol, 2003, 14: 561-566.
- 6. James A. Airway remodeling in asthma. Curr Opin PulmMed, 2005 ,11: 1-6.
- 7. Ammit AJ, Panettieri RA Jr. Airway smooth muscle cell hyperplasia:a therapeutic target in airway remodeling in asthma. Prog Cell Cycle Res, 2003, 5 : 49-57.
- 8. Shore SA, Fredberg JJ. Obesity, smooth muscle, and airway hyperresponsiveness. J Allergy Clin Immunol, 2005 , 115: 925-927 .
- 9. Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun, 2006,345: 271-279.
- 10. Cong L, Gasser J, Zhao J, et al. Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells,HEC-1-A and RL95-2. Endocr Relat Cancer, 2007, 14; 713-720.
- 11. Konturek PC, Burnat G, Rau T, et al. Effect of adiponectin and ghrelin on apoptosis of barrett adenocarcinoma cell line. Dig Dis Sci, 2008, 53: 597 -605.
- 12. Igata M, Motoshima H, Tsuruzoe K, et al. Adenosine monophosphateactivated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res, 2005, 97: 837 -844.
- 13. Nagata D, Takeda R, Sata M, et al. AMP-activated protein kinase inhibits angiotensin II-stimulated vascular smooth muscle cell proliferation. Circulation, 2004, 110 : 444-451 .
- 14. Ratnovsky A, Mellema M, An SS, et al. Airway smooth muscle proliferation and mechanics: effects of AMP kinase agonists. Mol Cell Biomech, 2007 , 4: 143-157.
- 15. Motoshima H, Goldstein BJ, Igata M, et al. AMPK and cell proliferation-AMPK as a therapeutic target for atherosclerosis and cancer. J Physiol, 2006, 574( Pt 1) : 63-71.