摘要
[目的]研究褪黑素(melatonin,MT)对矽肺大鼠肺纤维化的影响及其可能机制。[方法]将72只SPF级SD雄性大鼠,随机分为4组(对照组、MT组、染尘组及MT+染尘组),每组18只。对照组及MT组采用气管插管灌注法,一次性气管内注入1 m L生理盐水,其他两组采用同样方法注入50 mg/m L的二氧化硅悬液1 m L。每天给予MT组、MT+染尘组腹腔注射MT(10 mg/kg),而染尘组及对照组给予腹腔注射同体积生理盐水。每组分别于染毒后第7、14、28天随机处死6只大鼠。观察大鼠的肺脏器系数、肺组织形态,测定肺组织羟脯氨酸(Hyp)含量、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、肺组织核转录因子-κB(NF-κB)的表达。[结果]MT+染尘组大鼠肺泡炎症细胞浸润、充血水肿、肺间质纤维化的程度较染尘组相比有明显改善;与同期染尘组大鼠相比,MT+染尘组大鼠肺脏器系数、Hyp含量、MDA含量,SOD活性增加,差异均有统计学意义(均P<0.05)。Western blot检测结果显示,MT+染尘组大鼠肺组织NF-κB蛋白表达量(0.36±0.02)低于染尘组(0.48±0.01),差异有统计学意义(P<0.05)。[结论]褪黑素对矽肺大鼠肺纤维化有保护作用,其作用机制可能是通过改善机体氧化/抗氧化系统的失衡、抗炎,从而减少纤维化的形成。
[ Objective ] To test the potential effect and mechanism of melatonin （MT） on silica induced pulmonary fibrosis in rats. [ Methods ] Totally 72 specific-pathogen-free SD male rats were randomly divided into four groups （n=18 for each group）： control, MT, dust exposure, and MT＋dust exposure groups. The rats in the control group and the MT group were injected with 1 mL saline by intratracheal instillation, and those in the other two groups were injected with 1 mL silica suspension （50 mg/mL） by intratracheal instillation. After administration of silica or saline, the MT group and the MT＋dust exposure group were additionally intraperitoneally injected with MT （10 mg/kg）, while the control group and the dust exposure group were intraperitoneally injected with saline （10 mL/kg） every day. Six rats of each group were sacrificed 7, 14, and 28 days after exposure. Pulmonary organ coefficient was calculated and lung histomorphology was observed for each group. Hydroxyproline （Hyp） content, superoxide dismutase （SOD） activity, malondialdehyde （MDA） content, and the expression of nuclear factor kappa B （NF-KB） protein in lung tissues were evaluated. [ Results ] The MT＋ dust exposure group showed reduced lung inflammation, congestion, edema, and interstitial fibrosis compared with the dust exposure group. Compared with the dust exposure group at the same stage, the pulmonary organ coefficients, Hyp content, and MDA content were decreased, while the SOD activity was increased in the MT＋dust exposure group （Ps 〈 0.05）. Western blot analysis results showed that the expression of NF-κB protein （0.36±0.02） in lung tissue of the MT＋dust exposure group was lower than that of the dust exposure group （0.48±0.01） （P〈0.05）.[ Conclusion ] MT has a protective effect on silica induced lung fibrosis in rats. Its mechanism may be related to the improvement of oxidant/antioxidant system imbalance and anti-inflammatory, thus reducing fibrosis.
出处
《环境与职业医学》
CAS
CSCD
北大核心
2017年第7期642-647,共6页
Journal of Environmental and Occupational Medicine
关键词
褪黑素
矽肺
大鼠
抗氧化
肺纤维化
melatonin
dust exposure
rat
antioxidation
pulmonary fibrosis
