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Wen-Jie Ji Yong-Qiang Ma Xin Zhou Yi-Dan Zhang Rui-Yi Lu Zhao-Zeng Guo Hai-Ying Sun Dao-Chuan Hu Guo-Hong Yang Yu-Ming Li Lu-Qing Wei 《PloS one》2013,8(11)
Background
Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis.Methodology/Principal Findings
We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6Chi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation.Conclusions/Significance
The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching. 相似文献106.
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银杏叶提取物对糖尿病大鼠心肌损伤的防护作用 总被引:9,自引:0,他引:9
目的:研究银杏叶提取物(EGb)对糖尿病大鼠心肌的防护作用.方法:用光镜和透射电镜观察EGb对糖尿病大鼠心肌的形态学改变,并测定心肌组织内超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)、结构型一氧化氮合酶(cNOS)、诱导型一氧化氮合酶(iNOS)的活性及一氧化氮(NO)、丙二醛(MDA)的含量.结果:糖尿病大鼠心肌光镜下主要表现为心肌细胞空泡变性及心肌纤维局灶性溶解;电镜下主要表现为心肌线粒体肿胀,嵴变短,肌原纤维溶解;SOD活性下降,NOS、iNOS活性及MDA、NO含量增高.EGb治疗组病变明显减轻,EGb治疗组心肌组织内SOD活性明显高于糖尿病组,NOS、iNOS活性及MDA、NO含量低于糖尿病组.结论:EGb可能通过抗脂质过氧化作用和降低NO水平而对糖尿病心肌产生保护作用. 相似文献
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Powdery mildew disease caused by Blumeria graminis f. sp. tritici (Bgt) is an economically important disease in wheat worldwide. The identification of germplasms resistant to the disease can not
only facilitate the breeding of resistant cultivars, but can also broaden the diversity of resistance genes. The Mexican M53
is a synthetic hexaploid wheat line developed at the International Maize and Wheat Improvement Center (CIMMYT) from the cross
between Triticum durum and Aegilops tauschii249. Infection of M53 with 15 different pathogen races revealed that the resistance in M53 was race-dependent and effective
against the majority of the tested Bgt races, including the race 15 predominant in the Beijing wheat growing area. Inoculation of the parents of M53 with the race
15 demonstrated that M53 and Ae. tauschii249 were resistant, whereas T. durum was susceptible. The inoculation of three segregating F2 populations developed from the crosses between M53 and three susceptible Chinese wheat cultivars with the race 15 showed
that the resistant gene in M53 segregated in a single dominant manner. Amplified fragment length polymorphism (AFLP) and simple
sequence repeat (SSR) markers were used to map the gene in a segregating F2 population consisting of 213 lines developed from the cross Wan7107 × M53. Two closely linked AFLP markers, Apm109 and Apm161, were identified to flank the gene with genetic distances of 1.0 cM and 3.0 cM, respectively. The recognized gene was assigned
to the long arm of chromosome 5D as determined by three linked SSR markers, Xwmc289b, Xgwm583, and Xgwm292, and by the physical mapping of Apm109 using Chinese Spring nullisomic–tetrasomic and ditelosomic stocks. The resistance gene identified in M53, temporarily designated
as Pm-M53, could be used in local wheat-breeding programs to improve powdery mildew resistance. 相似文献