目的 探討不同劑量阿托伐他汀對(duì)博萊霉素( BLM) 所致大鼠肺纖維化的治療作用。方法 健康雌性SD 大鼠75 只隨機(jī)分為對(duì)照組、模型組、10 mg /kg 治療組、20 mg/ kg 治療組及40 mg / kg治療組, 每組15 只。模型組和治療組動(dòng)物均一次性氣管內(nèi)灌注BLM( 5 mg / kg) , 對(duì)照組灌注等體積生理鹽水。于灌注BLM后第2 d 開(kāi)始, 治療組按照分組劑量每日給予阿托伐他汀灌胃治療,對(duì)照組和模型組給予生理鹽水灌胃。各組于造模后第1、2 和4 周分別隨機(jī)選取5 只大鼠腹主動(dòng)脈采血查動(dòng)脈血?dú)? 隨后處死動(dòng)物取肺組織, 行HE 染色和Masson 染色。免疫組化檢測(cè)肺組織中轉(zhuǎn)化生長(zhǎng)因子β1 ( TGF-β1 ) 和結(jié)締組織生長(zhǎng)因子( CTGF) 變化。結(jié)果 各時(shí)間點(diǎn)治療組大鼠PaO2 均隨治療劑量增大逐漸升高, 同一組內(nèi)則隨時(shí)間延長(zhǎng)逐漸升高; 肺組織中TGF-β1 和CTGF 的表達(dá)量隨時(shí)間延長(zhǎng)逐漸減少。各時(shí)間點(diǎn)治療組TGF-β1 和CTGF 的表達(dá)量均較模型組明顯減少, 且治療劑量越大TGF-β1 和CTGF 的表達(dá)減少越明顯。結(jié)論 阿托伐他汀對(duì)博萊霉素所致的大鼠肺纖維化具有明顯治療作用, 且呈劑量依賴性及療程依賴性。
引用本文： 張曉萍,邵潤(rùn)霞,李付華. 不同劑量阿托伐他汀對(duì)肺纖維化大鼠的治療作用. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2009, 09(6): 580-584. doi: 復(fù)制
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- 1. Nègre-Aminou P, van Vliet AK, van Erck M, et al. Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibitors; comparison with other human cell types. Biochim Biophys Acta, 1997, 1345: 259-268.
- 2. Snider GL, Celli BR, Goldstein RH, et al. Chronic interstitial pulmonary fibrosis produced in hamasters by endotracheal bleomycin.Am Rev Respir Dis, 1978, 117: 289-297.
- 3. Wen FQ, Kohyama T, Sk ld CM, et al. Glucocorticoids molecular TGF-beta production by human fetal lung fibroblast. Inflammation,2003, 27: 9-19.
- 4. Crean JK, Finlay D,Murphy M, et al. The role of p42 / p44 MAPKand protein kinase B in connective tissue growth factor induced extracellular matrix protein production, cell migration, and actin cytoskeletal rearrangement in human mesangial Cells. J Biol Chem,2002, 277: 44187-44194.
- 5. 王浩凌, 謝敏, 劉濤. γ干擾素對(duì)博萊霉素誘導(dǎo)的大鼠肺纖維化的干預(yù)作用. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2007, 6: 105-109.
- 6. Bellosta S, Ferri N, Arnaboldi L, et al. Pleiotropic effects of statins in athero sclerosis and diabetes. Diabetes Care, 2000, 23 : B72 -B78 .
- 7. Watts KL, Sampson EM, Schultz GS, et al. Simvastatin Inhibits Growth Factor Expression and modulates profibrogenic markers in lung fibroblasts. AmJ Respir Cell Mol Biol, 2005, 32: 290- 300.