Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Shanghai Key Laboratory of Meteorology and Health, Shanghai, China.
Environ Sci Pollut Res Int. 2020 Jun;27(17):21311-21319. doi: 10.1007/s11356-020-08624-4. Epub 2020 Apr 8.
Both the epidemiological and animal experimental studies have reported the association between PM and respiratory, cardiovascular, and metabolic diseases. However, the study linking PM and hepatic injury is few, and the relative mechanism has not been fully elucidated. Thirty-two 6-week-old male C57BL/6 mice were exposed to filtered air (FA) or concentrated PM for 12 weeks using Shanghai Meteorological and Environmental Animal Exposure System ("Shanghai-METAS"), respectively. At week 11, the mice began to be treated with intraperitoneal injection of normal 0.9% saline or AMPK activator (AICAR). The mRNA levels of IL-6 and TNF-α, and protein expressions of AMPK, GLUT4, NF-κB, p38MAPK, ERK, and JNK in the liver and UCP-1 in brown adipose tissue (BAT) were measured. Meanwhile, histopathological examination both in the liver and BAT was performed to evaluate the histopathological changes. PM exposure induced steatosis, hepatocyte ballooning, lobular and portal inflammation in the liver, and the brown adipocyte swelling in BAT. The results found that PM mice displayed higher IL-6, TNF-α, NF-κB, and JNK expression and lower AMPK, GLUT4, and UCP-1 when compared with FA mice. The AICAR injection upregulated the expressions of GLUT4 in the liver of PM-AIC mice when compared with the PM mice. However, there were no significant effects of AICAR on histopathological condition. The current study showed that ambient PM exposure might induce the hepatic injury along with the lipid metabolism disorder in BAT. AMPK activation can ameliorate most of the harmful effects and might become the potential target for treating PM-induced hepatic injury.
两项流行病学和动物实验研究都报告了 PM 与呼吸、心血管和代谢疾病之间的关联。然而，将 PM 与肝损伤联系起来的研究很少，其相关机制尚未完全阐明。32 只 6 周龄雄性 C57BL/6 小鼠分别使用上海气象环境动物暴露系统（“上海-METAS”）暴露于过滤空气（FA）或浓缩 PM 12 周。在第 11 周，小鼠开始接受腹腔注射生理盐水或 AMPK 激活剂（AICAR）。测量肝脏和棕色脂肪组织（BAT）中 IL-6 和 TNF-α 的 mRNA 水平以及 AMPK、GLUT4、NF-κB、p38MAPK、ERK 和 JNK 的蛋白表达和 UCP-1。同时，对肝脏和 BAT 进行组织病理学检查，以评估组织病理学变化。PM 暴露导致肝脏脂肪变性、肝细胞气球样变、小叶和门脉炎症以及棕色脂肪细胞肿胀。结果发现，与 FA 组相比，PM 组小鼠的 IL-6、TNF-α、NF-κB 和 JNK 表达更高，而 AMPK、GLUT4 和 UCP-1 表达更低。与 PM 组相比，PM-AIC 组的 AICAR 注射使 GLUT4 在肝脏中的表达上调。然而，AICAR 对组织病理学状况没有显著影响。本研究表明，环境 PM 暴露可能导致肝脏损伤以及 BAT 中脂质代谢紊乱。AMPK 激活可改善大部分有害影响，可能成为治疗 PM 诱导的肝损伤的潜在靶点。
