本文選題：急性肺損傷 + 右美托咪定��； 參考：《濱州醫(yī)學(xué)院》2015年碩士論文

【摘要】：目的：右美托咪定是一種新型的α2受體激動(dòng)劑,因其具有鎮(zhèn)痛鎮(zhèn)靜的效果,被越來越多的應(yīng)用到重癥監(jiān)護(hù)病房,并且它作為一種麻醉輔助用藥得到廣泛應(yīng)用。目前,右美托咪定的抗炎機(jī)制成為研究的熱點(diǎn),本文探討右美托咪定對于脂多糖誘導(dǎo)的小鼠急性肺損傷的抗炎作用及可能的分子機(jī)制。方法：50只清潔級小鼠被隨機(jī)分為五組：正常組(Control組)、模型組(LPS組)、右美托咪定預(yù)處理組Dex (25μg/kg)+LPS組和Dex (50μg/kg)+LPS組、地塞米松預(yù)處理對照組(DXM+LPS組)。小鼠被腹腔注射5mg/kg脂多糖建立急性肺損傷模型,與此同時(shí),Control組小鼠腹腔注射生理鹽水,右美托咪定和地塞米松(1mg/kg)分別于脂多糖處理之前1小時(shí)腹腔注射。脂多糖處理后6小時(shí),對小鼠行支氣管肺泡灌洗,并取血、取小鼠的肺組織。小鼠的部分肺組織被用來測定濕干比重；石蠟切片后染色,顯微鏡下分析肺組織病理學(xué)改變；用Elisa試劑盒檢測支氣管肺泡灌洗液和血漿中細(xì)胞因子；BCA方法檢測支氣管肺泡灌洗液中總的蛋白含量；利用RT-PCR技術(shù)檢測肺組織中相關(guān)mRNA的表達(dá)；Westorn Blot方法被用來檢測肺組織中MAPK信號通路以及p38 MAPK-HSP27通路相關(guān)蛋白的表達(dá)。結(jié)果：實(shí)驗(yàn)結(jié)果表明,與正常組比較,LPS組小鼠表現(xiàn)出明顯的肺水腫和肺組織病理學(xué)改變,而右美托咪定預(yù)處理組和地塞米松處理組小鼠的肺組織水腫程度明顯減輕,肺組織病理學(xué)改變減輕,肺組織病理學(xué)評分明顯降低。同時(shí),與Control組比較,LPS組的小鼠支氣管肺泡灌洗液中蛋白含量和細(xì)胞因子(TNF-α,IL-1β)的濃度增加明顯,而右美托咪定和地塞米松處理組小鼠的上述指標(biāo)明顯減少。同時(shí),小鼠血漿中的細(xì)胞因子(TNF-α,IL-1β)含量也顯示出LPS組小鼠的比Control組明顯增加,而Dex (25μg/kg)+LPS組和Dex (50μg/kg)+LPS組小鼠血漿中的TNF-α和IL-1β比LPS組明顯的減少,DXM+LPS組小鼠血漿中的細(xì)胞因子含量與右美托咪定組的相近,比LPS組的含量減少明顯。PCR結(jié)果也表明LPS組肺組織中細(xì)胞因子(TNF-α,IL-6) mRNA的表達(dá)量顯著升高而右美托咪定和地塞米松預(yù)處理后的表達(dá)量明顯減少。另外,免疫印跡的條帶分析顯示右美托咪定能夠抑制MAPK信號通路以及p38 MAPK-HSP27通路的激活。結(jié)論：右美托咪定顯著地減輕脂多糖導(dǎo)致的小鼠急性肺損傷,其機(jī)制可能是右美托咪定抑制MAPK相關(guān)信號通路的激活從而減輕炎癥反應(yīng)。因此,右美托咪定可能會(huì)對治療膿毒癥導(dǎo)致的急性肺損傷患者提供新的方向。
[Abstract]:Objective: Dexmedetomidine is a new type of alpha 2 receptor agonist. Because of its analgesic and sedative effect, it has been used more and more in intensive care unit, and it is widely used as a kind of anesthetic adjuvant. Right metomomidine has become a hot spot. The anti-inflammatory effect and possible molecular mechanism of sugar induced acute lung injury in mice. Methods: 50 clean mice were randomly divided into five groups: normal group (group Control), model group (group LPS), Dex (25 u g/kg) +LPS group and Dex (50 g/kg) +LPS group, dexamethasone preconditioning group (DXM+LPS group). Mice were treated with abdominal cavity. 5mg/kg lipopolysaccharide was injected into an acute lung injury model. At the same time, rats in group Control were intraperitoneally injected with saline, right metomomidin and dexamethasone (1mg/kg) were intraperitoneally injected 1 hours before lipopolysaccharide treatment. 6 hours after lipopolysaccharide treatment, the mice were treated with bronchoalveolar lavage, and the lung tissue of mice was taken from the mice. The lung tissue was used to determine the specific gravity of the wet dry; the paraffin section was stained, the pathological changes of lung tissue were analyzed under the microscope; the cytokine in bronchoalveolar lavage fluid and plasma were detected by Elisa kit; the total protein content in the bronchoalveolar lavage fluid was detected by the BCA method; and the expression of related mRNA in the lung tissue was detected by RT-PCR technique. The Westorn Blot method was used to detect the MAPK signaling pathway in lung tissue and the expression of p38 MAPK-HSP27 pathway related proteins. Results: experimental results showed that compared with the normal group, the mice of group LPS showed obvious pulmonary edema and pulmonary histopathological changes, while the lung tissues of dexmeimidine preconditioning group and dexamethasone treated group were compared with the normal group. The degree of edema was obviously reduced, the pathological changes of lung tissue were reduced, and the score of lung histopathology decreased obviously. At the same time, the concentration of protein and cytokine (TNF- alpha, IL-1 beta) in the bronchoalveolar lavage fluid of the LPS group increased significantly compared with the Control group, but the above indexes in the right metomomidin and dexamethasone treatment group were significantly reduced. At the same time, the content of cytokine (TNF- alpha, IL-1 beta) in the mice plasma also showed that the LPS group was significantly higher than the Control group, while the TNF- alpha and IL-1 beta in the plasma of Dex (25 u g/kg) +LPS group and Dex (50 g/kg) +LPS group were significantly lower than those in the group. The decrease of the content of.PCR in group LPS also showed that the expression of cytokine (TNF-, IL-6) mRNA in the lung tissue of LPS group was significantly increased and the expression of dexmedetomidin and dexamethasone decreased significantly. Conclusion: dexmedetomidin significantly alleviates acute lung injury induced by lipopolysaccharide in mice. The mechanism may be that dexmedetomidine inhibits the activation of MAPK related signaling pathways and thus alleviates the inflammatory response. Therefore, dexmedetomidine may provide a new direction for patients with acute lung injury caused by sepsis.

【學(xué)位授予單位】：濱州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R614

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本文編號：1802843