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钩藤碱固体脂质纳米粒对哮喘小鼠miR-155/p38 MAPK轴的影响
引用本文:王盟,帕力姑·买买提力,李慧,吕传峰.钩藤碱固体脂质纳米粒对哮喘小鼠miR-155/p38 MAPK轴的影响[J].天津医药,2021,49(11):1154-1158.
作者姓名:王盟  帕力姑·买买提力  李慧  吕传峰
作者单位:1山东省济宁市第一人民医院医务部(邮编272000);2新疆维吾尔自治区英吉沙县人民医院儿科
基金项目:山东省重点研发计划项目资助(2019GSF108172);吴阶平医学基金会资助项目(320.6750);新疆维吾尔自治区自然科学基金资助(2021D01F19)
摘    要:目的 观察钩藤碱固体脂质纳米粒(Rhy-SLN)对支气管哮喘模型小鼠微小RNA-155(miR-155)/p38丝裂原活化蛋白激酶(p38 MAPK)轴的影响。方法 15只BALB/c小鼠随机均分为正常对照组、模型组和Rhy-SLN组。Rhy-SLN组小鼠行鼻内氢氧化铝致敏操作前以Rhy-SLN(50 mg/kg)灌胃;正常对照组和模型组给予等量生理盐水。干预结束后,肺泡灌洗液涂片观察嗜酸粒细胞的数量;HE染色观察小鼠肺组织病理改变情况;酶联免疫吸附试验(ELISA)法检测小鼠免疫球蛋白E(IgE)、白细胞介素(IL)-13水平;羟脯氨酸测试盒检测小鼠肺组织中羟脯氨酸水平;Werstern blot检测小鼠肺组织(α-SMA)、胶原蛋白Ⅰ(collagen Ⅰ)、p38 MAPK、p-p38 MAPK蛋白表达水平;荧光定量聚合酶链反应(qPCR)检测小鼠肺组织miR-155 mRNA表达水平。结果 与模型组比较,Rhy-SLN组可以降低哮喘小鼠肺泡灌洗液中嗜酸粒细胞的数目、血清中IgE和肺泡灌洗液中IL-13的水平(P<0.05);减轻肺组织炎性细胞浸润;降低肺组织中α-SMA、collagenⅠ、羟脯氨酸和p-p38 MAPK的表达(P<0.05);上调小鼠肺组织中miR-155的表达水平(P<0.05)。结论 Rhy-SLN可缓解小鼠哮喘,其机制可能与调节miR-155/p38 MAPK轴,降低气道的炎症反应有关。

关 键 词:哮喘  疾病模型  动物  钩藤碱  微RNAs  p38丝裂原活化蛋白激酶类  固体脂质纳米粒  微小RNA-155    
收稿时间:2021-03-29
修稿时间:2021-06-11

Effects of rhynchophylline solid lipid nanoparticles on miR-155/p38 MAPK axis in asthmatic mice
WANG Meng,Paligu·Maimaitili,LI Hui,LYU Chuan-feng.Effects of rhynchophylline solid lipid nanoparticles on miR-155/p38 MAPK axis in asthmatic mice[J].Tianjin Medical Journal,2021,49(11):1154-1158.
Authors:WANG Meng  Paligu·Maimaitili  LI Hui  LYU Chuan-feng
Institution:1 Department of Medicine, Jining NO.1 People's Hospital, Jining 272000, China; 2 Department of Paediatrics, Yingjisha People's Hospital, Xinjiang Uygur Autonomous Regions
Abstract:Objective To observe the effect of rhynchophylline solid lipid nanoparticles (Rhy-SLN) on the microRNA-155/p38 mitogen activated protein kinase (p38 MAPK) axis in asthmatic mice. Methods Fifteen BALB/c mice were randomly divided into the normal control group, the model group and the Rhy-SLN group. The mice in Rhy-SLN group were given the Rhy-SLN (50 mg/kg) before each sensitization operation of aluminum hydroxide. The normal control group and the model group were given equal amount of normal saline. After intervention, the number of eosinophils was observed by the smear of alveoli lavage. HE staining was used to observe the pathological changes of lung tissue in mice. The activities of immunoglobulin E (IgE) and interleukin-13 (IL-13) in mice were determined by ELISA. The hydroxyproline level in the lung tissue of mice was detected by hydroxyproline test. Western blot assay was used to detect expression levels of α-SMA, collagenⅠ, p38 MAPK and p-p38 MAPK in lung tissue of mice. The expression of miR-155 in mouse lung tissue was detected by RT-PCR. Results The number of eosinophils in BALF, the serum level of IgE and IL-13 in BALF of asthmatic mice were decreased in the Rhy-SLN group compared with those of the model group (P<0.05). Rhy-SLN can reduce the infiltration of inflammatory cells in lung tissue, reduce expression levels of α-SMA, collagen Ⅰ, hydroxyproline and p-p38 MAPK in lung tissue of asthmatic mice (P<0.05). The expression of miR-155 in lung tissue of mice was up regulated by Rhy-SLN (P<0.05). Conclusion Rhy-SLN can relieve asthma in mice, and its mechanism may be related to the regulation of the miR-155/p38 MAPK axis and reduction of airway inflammation.
Keywords:asthma  disease models  animal  Phynchophylline  microRNAs  p38 mitogen-activated protein kinases  solid lipid nanoparticles  microRNA-155  
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