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 探讨凋亡抑制蛋白Livin与凋亡蛋白Caspase-3在结直肠腺瘤-癌序列中的表达变化及其相关性。 方法 2006年7月—2009年12月，采用免疫组织化学染色链霉菌抗生物素蛋白-过氧化物酶链接法streptavidin-peroxidese，SP）法检测18例正常黏膜、84例结直肠腺瘤、72例结直肠癌中Livin及Caspase-3的表达情况。 结果 结直肠腺瘤组织中Livin蛋白的阳性表达率明显高于正常黏膜组织（Plt;0.05），而低于腺癌组（Plt;0.05）；腺瘤组内绒毛状腺瘤与管状腺瘤相比较，Livin蛋白表达率差异有统计学意义（Plt;0.05）。结直肠腺瘤组织中Caspase-3的阳性表达率明显高于正常黏膜组织（Plt;0.05）；而腺瘤组织与癌组织之间Caspase-3阳性表达率差异（Plt;0.05）；腺瘤组内绒毛状腺瘤与管状腺瘤相比较，Caspase-3蛋白阳性表达率差异无统计学意义（Pgt;0.05）。Livin表达与Caspase-3表达呈负相关（Plt;0.05）。 结论 凋亡抑制蛋白Livin参与了大肠肿瘤的发生，且在大肠腺瘤-腺癌阶段起到了重要作用；凋亡抑制蛋白Livin与Caspase-3表达呈负相关，抑制Caspase-3蛋白的活性可能是Livin促进结肠癌发生的途径之一。【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.