Fine Chalk Dust Induces Acute Heart Injury And Its Mechanism On Rats

Chalk is a common teaching tool.With the development of science and technology as well as the awareness of environmental protection,some teachers begin to select the whiteboard pens instead of useing chalk thus chalk demand is declined.But in many undeveloped and developing regions,due to the poor cultural infrastructure chalks are still widely used by the teachers.Also in some developed countries sunch as United States and Canada,chalk still widely used.During chalk teaching,a lot of chalk particles are produced.Large chalk particles will naturally settlement,while smaller chalk particle is dispersed in the air.Because fine chalk dust can penetrate into low respiratory tract,fine chalk particles will exert some adverse health effects.Numerous studies showed that PM_2.5 caused damage to the respiratory system and cardiovascular system.Yet evidence about the cardiac tissue damage of chalk PM_2.5 has not be reported.Therefore,it is necessary to study the effects of chalk PM_2.5 on cardiac fibrosis in rats.1.Wistar rats were exposed to different concentrations?2?8?32 mg/kg?of chalk PM_2.5 with intratracheal instillation method.Fibrosis-related genes(VEGF-A,TGF-?31,PDGF-D,PDGFR-?,TF,ColI?1?in cardiac tissue were analysised by real-time quantitative?RT-PCR?to study chalk PM_2.5-induced cardiac fibrosis.The results showed that:?1?chalk PM_2.5 had no effect on the expression of VEGF-A,PDGF-D,PDGFR-P mRNA compared with the control group.The expression of TGF-?₁ mRNA was upregulated by 32 mg/kg chalk PM_2.5,and NAC can repair this damage in some degree?P<0.05?.Exposure to chalk PM_2.5 at the doses of 8 mg/kg and 32 mg/kg,increased the expression of TF mRNA in a dose-dependent manner?P<0.05?,and NAC reduced the overexpression of TF,but there was no statistical difference.The expression of ColI?1 mRNA in myocardial tissue increased when the concentration of chalk PM_2.5 was 32 mg/kg?P<0.05?.And the overexpression of ColI?1 mRNA was reduced by NAC?P<0.05?.2.Expression of ERKs.JNK-2 signaling pathway as well as STAT-3?Smad-3?HO-1 and Nrf-2 gene in cardiac tissue were examined by Western-Blot and RT-PCR to research myocardial fibrosis mechanism induced by chalk PM_2.5 in rats.The results showed that:?1?Chalk PM_2.5 had no significant effect on the expression of JNK-2 protein?STAT-3 protein and Smad-3 protein.The expression of STAT-3 mRNA and Nrf-2 mRNA increased at the concentration of 32 mg/kg?P<0.05?,which can be reduced by NAC?P<0.05?.The expression of Smad-3 mRNA increased at the concentrations of 8 mg/kg and 32 mg/kg?P<0.05?,which can be reduced by NAC.The decrease of Smad-3 mRNA was statistically significant in the 8 mg/kg dose group only?P<0.05?.The expression of ERK1/2 protein increased in a dose-dependent manner,where 32 mg/kg dose group was statistically significant?P<0.05?.The expression of HO-1 mRNA decreased in a dose-dependent manner?P<0.05?.The expression of ERK1/2 protein and HO-1 mRNA caused by the 32 mg/kg chalk PM_2.5 can be respaired by NAC significantly?P<0.05?.In summary,when exposed to chalk PM_2.5 the expression level of fibrosis associated factor TF and TGF-?₁ mRNA increased,which caused the upregulated expression of ColI?l mRNA.The overexpression of TGF-?₁ and ColI?1 can be partially reduced by Antioxidant NAC.When exposed to Chalk PM_2.5,the expression of STAT-3 and Samd-3 mRNA also increased in the myocardial tissue,causing abnormal expression of oxidative stress markers of HO-1?Nrf-2.These results indicate that chalk PM_2.5 may induce cardiac oxidative stress,and further regulate the expression of genes related to fibrosis.While the expression of genes related to fibrosis may be related to ERK1/2 MAPK signaling pathway.