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辛伐他汀對(duì)小鼠巨細(xì)胞病毒肺炎Toll樣受體2表達(dá)的影響

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  本文關(guān)鍵詞: 辛伐他汀 巨細(xì)胞病毒 Toll樣受體 干擾素γ 單核細(xì)胞趨化蛋白 出處:《中國(guó)病理生理雜志》2017年10期  論文類型:期刊論文


【摘要】:目的:觀察辛伐他汀對(duì)小鼠巨細(xì)胞病毒(MCMV)肺炎小鼠肺組織Toll樣受體2(Toll-like receptor2,TLR-2)、干擾素γ(IFN-γ)和單核細(xì)胞趨化蛋白1(MCP-1)表達(dá)的影響,并探討辛伐他汀干預(yù)MCMV肺炎的可能機(jī)制。方法:將40只6~8周齡BALB/c小鼠隨機(jī)分成5組:正常對(duì)照(NC)組、MCMV感染組和辛伐他汀干預(yù)(SMV1、SMV2和SMV3)組。SMV1、SMV2和SMV3組分別在腹腔注射MCMV前7 d、與MCMV同時(shí)和MCMV感染后3 d給予辛伐他汀(50 mg·kg~(-1)·d~(-1),均連續(xù)給藥7 d)灌胃,NC組及MCMV組分別予以同體積的生理鹽水灌胃。HE染色觀察小鼠肺組織的病理改變,real-time PCR檢測(cè)MCMV DNA的變化,免疫組化和Western blot檢測(cè)肺組織中TLR-2的表達(dá),ELISA檢測(cè)肺組織中IFN-γ和MCP-1的變化。結(jié)果:與NC組相比,MCMV組肺組織病理染色顯示肺泡間質(zhì)水腫,肺泡壁增寬,內(nèi)可見大量炎性細(xì)胞浸潤(rùn);肺組織中TLR-2的表達(dá)增加,MCMV DNA含量升高,肺組織中炎癥因子IFN-γ和MCP-1明顯增多(P0.05)。辛伐他汀干預(yù)后,與MCMV組相比,肺組織病理改變較前減輕,TLR-2的表達(dá)下降(P0.05),MCMV DNA含量降低(P0.05),炎性因子IFN-γ和MCP-1明顯下降(P0.05),且SMV1組TLR-2的表達(dá)量及MCMV DNA含量下降較SMV2和SMV3組更明顯(P0.05),而SMV2和SMV3兩組相比差異無統(tǒng)計(jì)學(xué)顯著性。結(jié)論:辛伐他汀干預(yù)通過下調(diào)TLR-2信號(hào)通路而降低TLR-2的表達(dá),減少IFN-γ和MCP-1的分泌,并抑制MCMV DNA的復(fù)制,從而使肺組織的病理損害得以減輕;且提前給予辛伐他汀干預(yù)對(duì)預(yù)防MCMV的感染及減輕炎癥反應(yīng)具有重要作用。
[Abstract]:Objective: to observe the effect of simvastatin on Toll like receptor 2 (Toll-like receptor 2) and TLR-2 (TLR-2) in lung tissue of mice with cytomegalovirus (CMV) pneumonia. Interferon 緯 (IFN- 緯) and monocyte chemoattractant protein 1 (MCP-1). Methods: forty 6-week old BALB/c mice were randomly divided into 5 groups: normal control group. MCMV infection group and simvastatin intervention group (SMV1 + SMV2 and SMV3) group. SMV1 + SMV2 and SMV3 groups were injected MCMV 7 days before intraperitoneal injection. Simvastatin 50 mg 路kg-1) 路dan-1 was given to MCMV and MCMV 3 days after infection, and they were given intragastric administration for 7 days in a continuous dose of 5 mg 路kg ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路d ~ (-1). The pathological changes of lung tissue in NC group and MCMV group were observed by intragastric perfusion of normal saline in the same volume. The changes of MCMV DNA were detected by real-time PCR. Immunohistochemistry and Western blot were used to detect the expression of TLR-2 in lung tissue. Results: compared with NC group, the changes of IFN- 緯 and MCP-1 in lung tissue were detected by Elisa. In MCMV group, the alveolar interstitial edema was observed by pathological staining, the alveolar wall widened, and a large number of inflammatory cells were found in the alveolar wall. The expression of TLR-2 in lung tissue increased and the content of MCMV DNA increased, and the inflammatory factors IFN- 緯 and MCP-1 increased significantly. Compared with MCMV group, the pathological changes of lung tissue reduced the expression of TLR-2 and the content of MCMV DNA decreased (P0.05). The inflammatory factor IFN- 緯 and MCP-1 decreased significantly (P0.05). The expression of TLR-2 and the content of MCMV DNA in SMV1 group were significantly lower than those in SMV2 and SMV3 group (P 0.05). There was no significant difference between SMV2 and SMV3. Conclusion: simvastatin can decrease the expression of TLR-2 by down-regulating TLR-2 signaling pathway. The secretion of IFN- 緯 and MCP-1 was reduced, and the replication of MCMV DNA was inhibited, so that the pathological damage of lung tissue was alleviated. Early administration of simvastatin plays an important role in preventing MCMV infection and alleviating inflammation.
【作者單位】: 徐州市中心醫(yī)院呼吸內(nèi)科;徐州醫(yī)科大學(xué)附屬醫(yī)院呼吸內(nèi)科;
【基金】:江蘇省六大人才高峰項(xiàng)目(No.2014-WSN-043)
【分類號(hào)】:R563.1
【正文快照】: 巨細(xì)胞病毒(cytomegalovirus,CMV)是一種普遍存在的雙鏈DNA病毒,其通常呈隱性感染,多數(shù)感染者無臨床癥狀,但在一定條件下可以侵襲多個(gè)器官和系統(tǒng)產(chǎn)生嚴(yán)重疾病。數(shù)十年來,預(yù)防CMV感染的藥物不僅有限,而且結(jié)果往往不能令人滿意,因此,迫切需要一種新的更加安全有效的藥物以預(yù)防CM

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