白屈菜赤碱对大鼠肺组织的长期毒性作用及其对肺组织中NF-κB表达的影响

doi:10.13481/j.1671-587x.20190309

摘要/Abstract

摘要： 目的：观察白屈菜赤碱对大鼠肺组织形态的长期毒性作用及其对大鼠肺组织中核转录因子κB （NF-κB）表达的影响，探讨其引起大鼠肺损伤的相关机制。方法：将120只Wistar大鼠随机分为对照组（给予生理盐水）和低、中及高剂量白屈菜赤碱组（给予3.7、5.6和8.4 mg·kg^-1白屈菜赤碱），每组30只。观察各组大鼠一般情况；HE染色观察各组大鼠肺组织形态表现；酶联免疫吸附（ELISA）法检测各组大鼠血清白细胞介素6（IL-6）、白细胞介素8（IL-8）和肿瘤坏死因子α（TNF-α）水平；实时荧光定量PCR法检测各组大鼠肺组织中NF-κB和细胞间黏附分子1（ICAM-1） mRNA表达水平；Western blotting法检测各组大鼠肺组织中NF-κB和ICAM-1蛋白表达水平。结果：高剂量白屈菜赤碱组大鼠累积死亡率最高，其次为中和低剂量白屈菜赤碱组。各剂量白屈菜赤碱组大鼠体质量和摄食量均明显低于对照组（P<0.05），高剂量白屈菜赤碱组大鼠体质量和摄食量低于低和中剂量白屈菜赤碱组（P<0.05）。白屈菜赤碱能引起大鼠肺充血和血性腹水。HE染色，随着白屈菜赤碱剂量的增加，各剂量白屈莱赤碱组大鼠肺组织损伤加重。与对照组比较，各剂量白屈菜赤碱组大鼠血清IL-6、IL-8和TNF-α水平升高（P<0.05）；与低和中剂量白屈菜赤碱组比较，高剂量白屈菜赤碱组大鼠血清IL-6、IL-8和TNF-α水平升高（P<0.05）。与对照组比较，各剂量白屈菜赤碱组大鼠肺组织中NF-κB和ICAM-1 mRNA和蛋白表达水平升高（P<0.05），并呈剂量依赖性；与低和中剂量白屈菜赤碱组比较，高剂量白屈菜赤碱组大鼠肺组织中NF-κB和ICAM-1 mRNA和蛋白表达水平升高（P<0.05）。结论：白屈菜赤碱以剂量依赖的方式对大鼠肺组织产生长期毒性作用，中和高剂量白屈菜赤碱可能通过NF-κB活化和产生炎性细胞因子加重中毒性肺损伤。

关键词: 白屈菜赤碱, 长期毒性, 核转录因子κB, 肺损伤, 细胞间黏附分子1

Abstract: Objective:To observe the long-term toxicity of chelerythrine on the morphology of lung tissue and the expression level of nuclear factor-kappa B (NF-κB) in lung tissue of the rats, and to investigate the related mechanism which causing the lung tissue damage of rats. Methods:A total of 120 Wistar rats were divided into control group(given normal saline) and low (3.7 mg·kg^-1), moderate (5.6 mg·kg^-1), high (8.4 mg·kg^-1) dosages of chelerythrine groups (n=30).The general condition of rats in various groups was observed;HE staining was used to observe the morphology of lung tissue of the rats in various groups;the serum interleukin-6 (IL-6),interleukin-8(IL-8) and tumor necrosis factor-α (TNF-α) levels of the rats in various groups were measured by ELISA method;real-time fluorescence quantitative PCR and Western blotting methods were used to detect the mRNA and protein levels of NF-κB and intercellular adhesion molecule-1(ICAM-1). Results:The accumulative mortality of the rats in high dosage of chelerythrine group was the highest, followed by moderate and low dosages of chelerythrine groups. The body weights and food intakes of the rats in different dosages of chelerythrine groups were significantly lower than that in control group(P<0.05), while the body weight and food intake of the rats in high dosage of chelerythrine group were lower than those in low and moderate dosages of chelerythrine groups (P<0.05).Chelerythrine led to pulmonary congestion and bloody ascites of the rats.The HE staining results showed that the injuries of lung tissue in different dosages of chelerythrine groups were aggravated with the increasing of the dosage of chelerythrine. Compared with control group, the levels of IL-6, IL-8, and TNF-α in serum of the rats in different dosages of chelerythrine groups were increased significantly (P<0.05); compared with low and moderate dosages of chelerythrine groups, the levels of IL-6, IL-8, and TNF-α in serum of the rats in high dosage of chelerythrine group were increased significantly (P<0.05). Compared with control group, the expression levels of NF-κB and ICAM-1 mRNA and proteins in lung tissue of the the rats in different dosages of chelerythrine groups were increased significantly (P<0.05)in a dose-dependent manner; compared with low and moderate dosages of chelerythrine groups, the expression levels of NF-κB and ICAM-1 mRNA and proteins in lung tissue of the rats in high dosage of chelerythrine group were increased(P<0.05). Conclusion:Chelerythrine has a long-term toxic effect on lung tissue in a dose-dependent manner of the rats. Moderate and high dosages of chelerythrine may aggravate the toxic lung injury through activation of NF-κB and production of inflammatory cytokines.

Key words: chelerythrine, long term toxicity, nuclear factor-kappa B, lung injury, intercellular adhesion molecule-1

中图分类号:

刘建明, 刘宸辰, 刘新民, 曾明, 蒋群. 白屈菜赤碱对大鼠肺组织的长期毒性作用及其对肺组织中NF-κB表达的影响[J]. 吉林大学学报(医学版), 2019, 45(03): 518-523.

LIU Jianming, LIU Chenchen, LIU Xinmin, ZENG Ming, JIANG Qun. Long term toxicity of chelerythrine on lung tissue of rats and its effect on expression of NF-κB in lung tissue[J]. Journal of Jilin University(Medicine Edition), 2019, 45(03): 518-523.

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