阿托伐他汀鈣對香煙暴露大鼠肺血管炎癥模型組蛋白脫乙酰酶2的影響_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

何永鴻 ¹ ,  王宋平 ²

1. ;
2. ;

Corresponding?author：

王宋平, Email: 1808264282@qq.com

Keywords：

阿托伐他汀鈣; 蛋白脫乙酰酶2; 香煙暴露; 大鼠; 肺血管炎癥

DOI：

10.7507/1671-6205.202007090

Video：

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目的探討阿托伐他汀鈣對香煙暴露大鼠肺血管炎癥的作用及對肺組織、血清中組蛋白脫乙酰酶2（HADC2）的影響。方法將18只雌性SD大鼠隨機分為空白組（A組）、肺血管模型組（B組）、阿托伐他汀鈣干預組（C組），每組6只，使用煙熏加氣道滴入脂多糖經典造模方法對B組和C組大鼠進行香煙暴露肺血管炎癥模型制作，C組于第2天開始，每天熏煙前1 h用阿托伐他汀片灌胃治療，劑量5 mg/（kg·d），A、B組同期予以等量生理鹽水進行灌胃，35 d后處死大鼠。使用蘇木精–伊紅染色對大鼠各組病理組織進行染色，并對血管的炎癥進行評分。酶聯免疫吸附試驗檢測血清中HDAC2水平，蛋白印跡法檢查肺組織中HDAC2蛋白水平，實時熒光定量聚合酶鏈反應檢測肺組織HDAC2 mRNA水平。結果與A組比較，B、C組的肺血管炎癥明顯，但C組輕于B組。A組炎癥評分為（0.5±0.5）分，略低于C組［（1.7±0.7）分］，顯著低于B組［（2.7±1.0）分］，C組炎癥評分顯著低于B組。A組大鼠血清中HADC2水平為（12.76±0.63）ng/mL，略高于C組［（11.59±0.60）ng/mL］，但C、A組明顯高于B組［（2.27±0.42）ng/mL］，三組之間的差異有統計學意義（P<0.05）。B組大鼠肺組織中HDAC2蛋白表達明顯減少，而通過阿托伐他汀鈣干預后，C組的HDAC2表達（0.30±0.02）相較于B組（0.09±0.01）明顯增加，略低于A組（0.35±0.04）；A組（1.23±0.06）、C組（0.82±0.03）的HDAC2 mRNA水平明顯高于B組（0.27±0.02），三組之間的差異有統計學意義（P<0.05）。結論阿托伐他汀鈣可減輕香煙暴露大鼠肺血管炎癥的程度，其機制可能與增加HDAC2的表達有關。

Citation： 何永鴻, 王宋平. 阿托伐他汀鈣對香煙暴露大鼠肺血管炎癥模型組蛋白脫乙酰酶2的影響. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(12): 881-884. doi: 10.7507/1671-6205.202007090 Copy

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8.	樊梅, 鄧俊, 王宋平. 阿奇霉素對慢性阻塞性肺疾病大鼠肺血管重構的影響. 中國呼吸與危重監護雜志, 2018, 17(2): 128-133.
9.	Zhou Y, Tan X, Kuang W, et al. Erythromycin ameliorates cigarette-smoke-induced emphysema and inflammation in rats. Transl Res, 2012, 159(6): 464-472.
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11.	Lai T, Wu M, Zhang C, et al. HDAC2 attenuates airway inflammation by suppressing IL-17 A production in HDM-challenged mice. Am J Physiol Lung Cell Mol Physiol, 2019, 316(1): L269-L279.
12.	Khangura RK, Bali A, Jaggi AS, et al. Histone acetylation and histone deacetylation in neuropathic pain: An unresolved puzzle?. Eur J Pharmacol, 2017, 795: 36-42.
13.	李珊, 劉永哲, 黃慧, 等. 組蛋白去乙酰化酶在特發性肺纖維化和隱源性機化性肺炎發病機制中的作用. 中華結核和呼吸雜志, 2019, 42(5): 361-366.
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15.	Lee CS, Yi EH, Lee JK, et al. Simvastatin suppresses RANTES-mediated neutrophilia in polyinosinic-polycytidylic acid-induced pneumonia. Eur Respir J, 2013, 41(5): 1147-1156.

1. Bourbeau J, Celli BR, Criner GJ, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J, 2019, 53(5): 1900164.
2. McLaughlin VV, Shah SJ, Souza R, et al. Management of pulmonary arterial hypertension. J Am Coll Cardiol. 2015, 65(18): 1976-1997.
3. Celebi S, Celebi OO, Aydogdu S. Beyond lipids: antiarrhythmic effects of statins. Angiology, 2019, 70(3): 283.
4. Howard ML, Vincent AH. Statin effects on exacerbation rates, mortality, and inflammatory markers in patients with chronic obstructive pulmonary disease: a review of prospective studies. Pharmacotherapy, 2016, 36(5): 536-547.
5. Lu Y, Chang R, Yao J, et al. Effectiveness of long-term using statins in COPD - a network meta-analysis. Respir Res, 2019, 20(1): 17.
6. Chen F, Yang M, Wan C, et al. Efficacy and safety of statin therapy in pulmonary hypertension: a systematic review and meta-analysis. Ann Transl Med, 2019, 7(23): 786.
7. Pathak NN, Lingaraju MC, Balaganur V, et al. Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis. Inflamm Res, 2015, 64(3-4): 161-169.
8. 樊梅, 鄧俊, 王宋平. 阿奇霉素對慢性阻塞性肺疾病大鼠肺血管重構的影響. 中國呼吸與危重監護雜志, 2018, 17(2): 128-133.
9. Zhou Y, Tan X, Kuang W, et al. Erythromycin ameliorates cigarette-smoke-induced emphysema and inflammation in rats. Transl Res, 2012, 159(6): 464-472.
10. 曹路, 高寶安, 官莉, 等. 慢阻肺患者血清中組蛋白去乙酰化酶2 IL-1βIL-6及IL-17 A的水平及臨床意義. 河北醫學, 2019, 25(10): 1585-1588.
11. Lai T, Wu M, Zhang C, et al. HDAC2 attenuates airway inflammation by suppressing IL-17 A production in HDM-challenged mice. Am J Physiol Lung Cell Mol Physiol, 2019, 316(1): L269-L279.
12. Khangura RK, Bali A, Jaggi AS, et al. Histone acetylation and histone deacetylation in neuropathic pain: An unresolved puzzle?. Eur J Pharmacol, 2017, 795: 36-42.
13. 李珊, 劉永哲, 黃慧, 等. 組蛋白去乙酰化酶在特發性肺纖維化和隱源性機化性肺炎發病機制中的作用. 中華結核和呼吸雜志, 2019, 42(5): 361-366.
14. Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol, 2008, 121(3): 580-584.
15. Lee CS, Yi EH, Lee JK, et al. Simvastatin suppresses RANTES-mediated neutrophilia in polyinosinic-polycytidylic acid-induced pneumonia. Eur Respir J, 2013, 41(5): 1147-1156.

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阿托伐他汀鈣對香煙暴露大鼠肺血管炎癥模型組蛋白脫乙酰酶2的影響

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