PAS-Na 对锰暴露大鼠生长缓慢和激活炎症反应的预防作用。
Preventive impacts of PAS-Na on the slow growth and activated inflammatory responses in Mn-exposed rats.
机构信息
Department of Toxicology, School of Public Health, Guangxi Medical University, 530021, Nanning, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China.
Department of Toxicology, School of Public Health, Guangxi Medical University, 530021, Nanning, China.
出版信息
J Trace Elem Med Biol. 2019 Jul;54:134-141. doi: 10.1016/j.jtemb.2019.04.013. Epub 2019 Apr 25.
BACKGROUND
Sodium para-aminosalicylic acid (PAS-Na), an anti-tuberculosis drug, has been demonstrated its function in facilitating the Mn elimination in manganism patients and Mn-exposed models in vivo and improving the symptoms of Mn poisoning. But whether it can improve the growth retardation and inflammatory responses induced by Mn have not been reported.
OBJECTIVES
This study was designed to investigate the preventive effects of PAS-Na on the development of retardation and inflammatory responses in Mn-exposed rats.
METHODS
Male Sprague Dawley (SD) rats (8 weeks old, weighing 180 ± 20 g) were randomly divided into normal control group and Mn-exposed group in the 4 weeks experiment observation and normal control group, Mn-exposed group, PAS-Na preventive group and PAS-Na control group in the 8 weeks experiment observation. The Mn-exposed group received an intraperitoneal injection (i.p.) of 15 mg/kg MnCl and the normal control group i.p. physiological Saline in the same volume once a day for 4 or 8 weeks, 5 days per week. The PAS-Na preventive group i.p. 15 mg/kg MnCl along with back subcutaneous (s.c.) injection of 240 mg/kg PAS-Na once a day for 8 weeks, 5 days per week. PAS-Na control group received s.c. injection of 240 mg/kg PAS-Na along with i.p. injection of saline once daily. The body weight was determined once a week until the end of the experiment. The manganese contents in the blood were detected by graphite furnace atomic absorption spectrometry. The inflammatory factor levels (TNF-α, IL-1β, IL-6, and PGE2) in the blood were detected by using enzyme-linked immunosorbent assay (Elisa) and each organ taking from rats were weighed and recorded.
RESULTS
Mn exposure significantly suppressed the growth in rats and increased heart, liver, spleen and kidney coefficients as compared with the control group. The whole blood Mn level and serum levels of IL-1β, IL-6, PGE2, and TNF-α in sub-chronic Mn-exposure group were markedly higher than those in the control group. However, preventive treatment with PAS-Na obviously reduced the whole blood Mn level, the spleen and liver coefficients of the Mn-exposed rats. And serum levels of IL-1β and TNF-α were significantly reduced by 33.9% and 14.7% respectively in PAS-Na prevention group.
CONCLUSIONS
PAS-Na could improve the growth retardation and alleviate inflammatory responses in Mn-exposed rats.
背景
对氨基水杨酸钠（PAS-Na）是一种抗结核药物，已被证明在体内具有促进锰排出和改善锰中毒症状的功能。但是，它是否可以改善锰暴露引起的生长迟缓以及炎症反应尚未报道。
目的
本研究旨在探讨 PAS-Na 对锰暴露大鼠生长迟缓及炎症反应的预防作用。
方法
雄性 Sprague Dawley（SD）大鼠（8 周龄，体重 180±20g）随机分为 4 周实验观察的正常对照组和锰暴露组，以及 8 周实验观察的正常对照组、锰暴露组、PAS-Na 预防组和 PAS-Na 对照组。锰暴露组每天腹腔注射（ip）15mg/kg MnCl2，正常对照组腹腔注射等体积生理盐水，每周 5 天，共 4 或 8 周。PAS-Na 预防组每天 ip 注射 15mg/kg MnCl2，同时背部皮下（sc）注射 240mg/kg PAS-Na，每周 5 天，共 8 周。PAS-Na 对照组每天 sc 注射 240mg/kg PAS-Na，同时 ip 注射生理盐水。每周测定一次体重，直至实验结束。用石墨炉原子吸收光谱法测定血液中的锰含量。用酶联免疫吸附试验（ELISA）测定血液中炎症因子水平（TNF-α、IL-1β、IL-6 和 PGE2），并记录大鼠各器官的重量。
结果
与对照组相比，锰暴露组大鼠体重明显下降，心、肝、脾、肾系数增加。与对照组相比，亚慢性锰暴露组大鼠全血锰水平及血清 IL-1β、IL-6、PGE2 和 TNF-α水平明显升高。然而，PAS-Na 预防性治疗明显降低了锰暴露大鼠的全血锰水平和脾、肝系数。PAS-Na 预防组血清中 IL-1β和 TNF-α的水平分别降低了 33.9%和 14.7%。
结论
PAS-Na 可改善锰暴露大鼠的生长迟缓，并减轻炎症反应。
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