Objectives To investigate the effects of cryptotanshinone (CTS) on cigarette smoke (CS) -induced airway inflammation and oxidative stress in mice and the possible mechanisms. Methods BALB/c mice were exposed to CS for 4 weeks to establish airway inflammation model. CTS was given by intraperitoneal injection before CS exposure at a dosage of 30 mg·kg?1·d?1 or 15 mg﹒kg?1·d?1. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and detection of pro-inflammatory cytokine [interleukine (IL)-17, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α] levels. Lung tissue was collected for histological examination, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, immunohistochemistry and polymerase chain reaction for Muc5ac detection, and western blot for lectin-like oxidized low-density lipoprotein-1 receptor (LOX-1) and nuclear factor (NF)-κB. Results CTS administration attenuated CS exposure induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction, increased numbers of total cells, macrophages, and neutrophils, and decreased the releases of IL-17, MCP-1, TNF-α in BALF of mice. CS exposure could induce the elevation in MDA levels and decrease in SOD activities, markers of oxidative stress. CTS could attenuate these changes. CTS also attenuated CS induced up-regulation of the protein levels of LOX-1 and phosphorylated p65, down-regulation of the levels of NF-κB inhibitor α. Conclusion CTS alleviates the airway inflammation, oxidative stress and mucus hypersecretion induced by CS, which may be through the regulation of LOX-1 and NF-κB signaling pathway.
【摘要】 目的 探討凋亡抑制蛋白Livin與凋亡蛋白Caspase-3在結直腸腺瘤-癌序列中的表達變化及其相關性。 方法 2006年7月—2009年12月，采用免疫組織化學染色鏈霉菌抗生物素蛋白-過氧化物酶鏈接法streptavidin-peroxidese，SP）法檢測18例正常黏膜、84例結直腸腺瘤、72例結直腸癌中Livin及Caspase-3的表達情況。 結果 結直腸腺瘤組織中Livin蛋白的陽性表達率明顯高于正常黏膜組織（Plt;0.05），而低于腺癌組（Plt;0.05）；腺瘤組內絨毛狀腺瘤與管狀腺瘤相比較，Livin蛋白表達率差異有統計學意義（Plt;0.05）。結直腸腺瘤組織中Caspase-3的陽性表達率明顯高于正常黏膜組織（Plt;0.05）；而腺瘤組織與癌組織之間Caspase-3陽性表達率差異（Plt;0.05）；腺瘤組內絨毛狀腺瘤與管狀腺瘤相比較，Caspase-3蛋白陽性表達率差異無統計學意義（Pgt;0.05）。Livin表達與Caspase-3表達呈負相關（Plt;0.05）。 結論 凋亡抑制蛋白Livin參與了大腸腫瘤的發生，且在大腸腺瘤-腺癌階段起到了重要作用；凋亡抑制蛋白Livin與Caspase-3表達呈負相關，抑制Caspase-3蛋白的活性可能是Livin促進結腸癌發生的途徑之一。【Abstract】 Objective To investigate the expression of Livin and Caspase-3 among colorectal adenoma-carcinoma sequence, and to identify the relationship between Livin and Caspase-3 expression in colorectal adenoma-carcinoma sequence. Methods Formalin-fixed paraffin embedded colorectal tissues from 174 patients, including 84 adenomas, 72 carcinomas, and 18 normal mucosa, were examined for expression of Livin and Caspase-3 by streptavidin-peroxidase (SP) immunohistochemistry between July 2006 and December 2009. Results The positive rates of Livin protein expression in colorectal adenoma was significantly higher than that in normal mucosa (Plt;0.05), but lower than that in adenocarcinoma (Plt;0.05); the expression of Livin in tubular adenoma was significantly higher than that in villous adenoma (Plt;0.05). The positive rates of Caspase-3 protein expression in colorectal adenoma were significantly higher than that in normal mucosa and carcinoma (Plt;0.05), and the difference in positive rate of Caspase-3 expression was not significant between the villous adenoma and tubular adenoma (Pgt;0.05). Livin expression had negative correlation with the Caspase-3 expression (Pgt;0.05). Conclusion The difference in expression of Livin between adenoma and adenocarcinoma indicates the potential value of it in carcinogenesis of colorectal cancer, which suggestes that suppressing Caspase-3 protein activity is one of the channels by which livin promotes colorectal carcinogenesis.