【摘要】：目的:早期肺部炎癥和肺上皮間質(zhì)轉(zhuǎn)化(EMT)在肺纖維化過程起重要作用。越來越多的證據(jù)表明,骨化三醇(即活化型維生素D3)具有抗炎作用。本研究的目的是調(diào)查維生素D3對博來霉素誘導的早期肺部炎癥和隨后EMT的抑制效應。方法:成年C57BL/6J雄性小鼠(8周,24-26g),隨機分為PBS對照組(Control),BLM模型組(BLM),不同劑量維生素D3保護組(BLM+Vit D)。對照組給予氣管插管注射PBS,單純BLM組小鼠氣管內(nèi)插管注射BLM(3.0毫克/千克),不同劑量維生素D3保護組小鼠腹腔內(nèi)(i.p)注射不同劑量維生素D3(0.2、1.0或5.0 mg/kg)予以預處理。維生素D3預處理時間均為給予LPS前48 h、24 h、1h。BLM注射后24小時,7天和14天,取肺組織。部分肺臟組織經(jīng)4%多聚甲醛固定后制備石蠟包埋組織切片,用HE染色法觀察病理學改變,用Western Blot檢測肺組織p Akt/Akt,pp38,NF-κB p65水平,通過免疫組化檢測A-SMA和NF-κB p65水平,RT-PCR檢測各種細胞炎性因子表達。結果:維生素D3減輕BLM誘導的肺部炎癥細胞浸潤。BLM誘導肺部炎性細胞因子也被維生素D3抑制。,維生素D3減少BLM誘導NF-k B p65入核、減輕肺p38 MAPK和Akt磷酸化。進一步分析表明,BLM誘導的平滑肌肌動蛋白(a-SMA也被維生素D3抑制。維生素D3抑制BLM誘導的轉(zhuǎn)化生長因子1(TGF-b1)上調(diào)和Smad磷酸化。結論:維生素D3抑制BLM-誘導的早期肺部炎癥和隨后的EMT轉(zhuǎn)化。
[Abstract]:Objective: early pulmonary inflammation and pulmonary epithelial interstitial transformation (EMT) play an important role in the process of pulmonary fibrosis. There is growing evidence that calcitriol, or activated vitamin D 3, has anti-inflammatory effects. The aim of this study was to investigate the inhibitory effects of vitamin D 3 on bleomycin induced early pulmonary inflammation and subsequent EMT. Methods: adult C57BL/6J male mice (8-week-24 ~ 26g) were randomly divided into PBS control group (Control) / BLM model group), (BLM), treated group with different doses of vitamin D _ 3 (BLM Vit D). The control group was injected with endotracheal intubation, the mice of BLM group were injected with BLM (3.0 mg / kg), and the mice of different doses of vitamin D _ 3 (i.p) were pretreated with different doses of vitamin D _ 3 (0.2g 1.0 or 5.0 mg/kg). The pretreatment time of vitamin D _ 3 was 24 hours, 7 days and 14 days after administration of LPS. Paraffin-embedded tissue sections were prepared from some lung tissues fixed with 4% paraformaldehyde. Pathological changes were observed by HE staining, and the level of p65 in p Akt / AktP38 and NF- 魏 B p65 in lung tissue was detected by Western Blot. The levels of A-SMA and NF- 魏 B p65 were detected by immunohistochemistry and RT-PCR was used to detect the expression of various cytokines. Results: vitamin D _ 3 alleviated the infiltration of pulmonary inflammatory cells induced by BLM. BLM-induced pulmonary inflammatory cytokines were also inhibited by vitamin D _ 3. Vitamin D _ 3 decreased BLM induced NF-k B p65 entry into the nucleus and reduced p38 MAPK and Akt phosphorylation. Further analysis showed that smooth muscle actin (a-SMA) induced by BLM was also inhibited by vitamin D 3. Vitamin D 3 inhibits BLM induced up-regulation of transforming growth factor 1 (TGF-b1) and Smad phosphorylation. Conclusion: vitamin D 3 inhibits early lung inflammation induced by BLM- and subsequent EMT transformation.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R563

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