Pulmonary toxicities from a 90-day chronic inhalation study with carbon black nanoparticles in rats related to the systemical immune effects
Pulmonary toxicities from a 90-day chronic inhalation study with carbon black nanoparticles in rats related to the systemical immune effects
复制标题
一项对大鼠进行的 90 天慢性吸入炭黑纳米粒子研究显示的肺部毒性与系统免疫效应有关。
DOI：
10.2147/ijn.s198376
复制
发表时间：
2019-01-01
影响因子：
8
通讯作者：
Zhang, Rong
中科院分区：
文献类型：
--
作者：
Chu, Chen;Zhou, Lixiao;Zhang, Rong
背景：近年来，我国北方冬季雾霾污染严重。大气颗粒物（PM）对人体健康的潜在影响引起了人们的广泛关注。在可吸入粒径范围内，燃料来源的PM主要由炭黑（CB）纳米颗粒的聚集体组成。然而，仍然缺乏证据，特别是关于长期暴露，以解释纳米级CB的慢性效应和相关mechanism.Purpose：本研究的目的是确定纳米级CB的慢性效应的潜在机制。方法：将32只大鼠随机分为2组：30 mg/m3浓度的CB经鼻染毒组（90d，6 h/d）和对照组（清洁空气组）。暴露后处死一半大鼠，另一半大鼠恢复14天。每组8只大鼠使用通气式偏流全身体积描记器（WBP）进行肺功能测试。采用SDS-PAGE方法检测CB在大鼠肺组织中的沉积和滞留。HE染色观察组织病理学变化。TUNEL法和流式细胞术检测细胞凋亡。用市售ELISA试剂盒评价血清和肺组织中IL-6、IL-8、IL-17和TNF-α的水平。结果：经MPPD染毒90 d后，大鼠肺内CB负荷量为16 mg。在14天的恢复期内，暴露期结束时累积的CB量的14%从肺中清除。肺功能明显下降，经短期恢复后仍不能恢复。肺内可见成纤维细胞和肉芽肿形成。CB吸入后肺细胞凋亡和DNA损伤明显增加。CB染毒组大鼠肺组织细胞因子水平显著升高，而血清中细胞因子水平无显著变化。CB暴露后WBC、单核细胞和中性粒细胞计数分别增加1.72、3.13和2.73倍。接触CB后，CD 4+淋巴细胞百分率和CD 4 +/CD 8+比值明显升高。CB暴露后，外周血淋巴细胞刺激指数明显降低。CB染毒组胸腺和脾脏组织形态学改变，胸腺细胞早期凋亡增加2.36倍。结论：CB可引起局部或直接毒性和全身免疫毒性。直接免疫反应和全身免疫反应在CB所致肺损伤中起协同作用。
Background: Recent years, there occurs heavy haze pollution in northern China during wintertime. The potential influence of airborne particulate matter (PM) on human health attracts great concern. The fuel-derived PM in the inhalable size range is dominated by aggregates of nanoparticles of Carbon black (CB). However, there are still lack of evidences especially regarding long-term exposure to explain the chronic effects of nanoscaled CB and the relative mechanism.Purpose: The objective of this study was to identify the potential mechanism of chronic effects of nanoscale CB. The systemic toxicity, immune suppression or activity and local toxicity were evaluated.Methods: 32 rats were divided into 2 groups: 30 mg/m3 CB exposure (nose only, 90 d, 6h/d) and control (clean air). Half of rats were scarified after exposure and another half of rats recovered for 14 days. Eight rats in each group were executed the lung function tests using a ventilated bias flow whole body plethysmograph (WBP). SDS-PAGE protocol was used to detect the deposition and retention of CB in lung of rats. HE staining was used to observe the changes of histopathology. Cell apoptosis was examined by TUNEL assay or flow cytometry. The levels of IL-6, IL-8, IL-17 and TNF-alpha in serum and lung tissue were evaluated with commercially available ELISA kit. The peripheral blood cell counts were detected by Auto 5-diff hematology analyzer.Results: The lung burden of CB was 16 mg in lung of rats after a 90-day exposure by MPPD. Fourteen percentages of the amount of CB accumulated at the end of the exposure period was cleared from the lung during the 14 dys recovery period. The lung function was significantly decreased and could not recover after a short time recovery. The fibroblasts and granuloma formation were found in lung. The levels of apoptosis and DNA damages were significantly increased in lung cells after CB inhalation. The cytokines levels in lung but not in serum were significantly increased in CB exposure group. The cell counts of WBC, monocytes and neutrophils had 1.72, 3.13, and 2.73-fold increases after CB exposure, respectively. The percentages of CD4+ lymphocytes and the rates of CD4+/CD8+ were statistically increased after CB exposure. The stimulation indexes of the peripheral blood lymphocytes were significantly decreased after CB exposure. In the CB exposure group, the disrupted histomorphology of thymus and spleen were found as well as the early apoptotic thymocytes had a 2.36-fold increase.Conclusion: CB induced the localized or direct toxicity and systemic immune toxicity. The direct and systemic immune responses had a combined effect on the lung damages caused by CB.