Abstract:
Background Occupational silicosis is a respiratory disease that seriously threatens the life and health of related occupational practitioners. It is progressive and irreversible, and its mechanism and progression have not been fully elucidated.
Objective This experiment investigates the expression of succinate dehydrogenase (SDHA) mRNA in the lung of dust-exposed Wistar rats and changes of mitochondrial adenosine triphosphate (ATP) metabolism.
Methods Forty Wistar rats were randomly divided into a control group and three experimental groups, with 10 rats in each group. The rats in the experimental groups were exposed to 1 mL SiO2 (100 mg/mL) suspension by intratracheal instillation for only once, and were neutralized after 30, 60, and 120 days, respectively. The rats in the control group were treated with normal saline, and were neutralized 120 days later. Lung tissues were harvested to observe pathological changes using hematoxylin and eosin (HE) staining and electron microscopy. The relative expression of SDHA mRNA was measured by quantitative real-time PCR. The ATP content and Ca2+-Mg2+-ATPase activity of lung mitochondria were detected.
Results The pathological images of lung tissues stained with HE showed that pulmonary fibrosis was more obvious over time in the rats of the experimental groups. The pathological images of electron microscopy showed that the mitochondria in lung tissues of the experimental groups were swollen and destroyed compared with the control group. The relative expression levels of SDHA mRNA in the control group and the 30d, 60d, and 120d experimental groups were 1.08±0.34, 4.17±0.38, 1.96±0.43, and 0.44±0.40, respectively. Compared with the control group, the expression of SDHA mRNA in the 30d group was increased and that in the 120d group was reduced (P < 0.05). The contents of mitochondrial ATP in lung were:control group (402.20±85.18)μmol/g (normalized by protein in per g, thereafter), 30d group (700.35±98.60)μmol/g, 60d group (350.10±92.57)μmol/g, and 120d group (200.51±88.49)μmol/g, respectively. The activities of Ca2+-Mg2+-ATPase of mitochondria were:control group (3.96±2.51)×10-2 U/mg (normalized by protein in per g, thereafter), 30 d group (9.58±3.83)×10-2 U/mg, 60 d group (4.89±4.72)×10-2 U/mg, and 120 d group (2.51±3.97)×10-2 U/mg, respectively. The content of ATP and the activity of Ca2+-Mg2+-ATPase changed in the same way, which were higher in the 30 d group and lower in the 120 d group than those in the control group (P < 0.05).
Conclusion Dust inhalation could cause the expression of SDHA mRNA in rat lung tissues to peak first in an early stage, then gradually fall below normal level, and corresponding changes in ATP content and Ca2+-Mg2+-ATPase activity.