Acid sphingomyelinase mediates the noise-induced liver disorder in mice
Acid sphingomyelinase mediates the noise-induced liver disorder in mice
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DOI：
10.1111/1440-1681.13083
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发表时间：
2019-06-01
影响因子：
2.9
通讯作者：
Bao, Junxiang
中科院分区：
文献类型：
--
作者：
Meng, Xingxing;Gu, Zhenghui;Bao, Junxiang
噪声引起的肝脏结构和功能紊乱已经实现，但其潜在机制尚未明确，这限制了预防措施的引入。酸性鞘磷脂酶(ASM)/神经酰胺（Cer）通路的过度激活在各种刺激引起的肝细胞损伤中起着中心作用。我们的目的是研究它是否介导噪音引起的肝脏疾病的基础设施、脂质代谢、细胞凋亡和氧化应激。各组小鼠分别暴露于20-20k Hz、90-110 dB的宽带噪声环境中1、3、5、7天，每3小时/d。给予ASM抑制剂盐酸多虑平（DOX） 5 mg/kg/d灌胃。我们发现，5或7天的高强度宽带噪声暴露会导致肝细胞中显著的基础设施紊乱和脂滴储存。噪声刺激后肝脏组织中胆固醇、游离脂肪酸和甘油三酯含量显著升高。此外，噪声显著促进肝细胞凋亡和超氧化物的产生，提高血清中天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的活性。噪声暴露使肝组织酸性鞘磷脂酶活性和Cer生成升高，并在给予DOX后恢复正常。因此，DOX可显著减轻噪声暴露小鼠肝细胞或血清脂肪变性、细胞凋亡、氧化应激和酶促变化。综上所述，我们的研究结果表明，ASM/Cer通路参与了宽带噪声引起的小鼠肝损伤。
Noise-induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over-activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20-20k Hz, 90-110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.