Influence of Paraquat Poisoning on the Expression of Toll-like Receptor 4 in Myocardial Damage Following in Mice and Its Significance / 中国医科大学学报

ABSTRACT

Objective To clarify the role and significance of Toll?like receptor 4(TLR4)in myocardial damage following paraquat(PQ)poisoning in mice. Methods Male wild type C57BL/6J mice(WT)and male TLR4 deficient mice(TLR4?ko)were divided into four groups in the study(1)control group(WT mice,n=6);(2)TLR4?ko group(TLR4?ko mice,n=6);(3)WT+PQ group(WT mice,n=30);(4)TLR4?ko+PQ group (TLR4?ko mice,n=30). The mice in group 1 and group 2 were injected intraperitoneally with saline;mice in group 3 and group 4 were injected in?traperitoneally with 75 mg/kg of PQ. At 2 h,4 h,8 h,16 h and 24 h after PQ administration,6 mice of WT+PQ group and TLR4?ko+PQ group were euthanized and the heart tissue specimens were harvested. All the specimens were analysed by histology,while the expression of TLR4 mRNA was only detected in samples of WT+PQ mice. The specimens at 2 h,8 h and 24 h after PQ administration were used for cytokines detection for WT+PQ group and TLR4?ko+PQ group;in addition,Western blot analysis was performed for WT+PQ group. At 8 h after treatment,control mice and TLR4?ko mice were euthanized by the same method. Mice were anesthetized for cardiac geometry and functional assessment using a 2?D guide M?mode echocardiography at 8 h following injection of either PQ or saline. Results During myocardial damage due to PQ exposure in WT+PQ mice,obvious histopathological changes were observed,as well as a noticeable decrease of heart function and increased expressions of TNF?αand IL?1β. Compared with the WT mice,TNF?αand IL?1βprotein levels,changes in heart function and histopathological changes were significantly attenuated following PQ exposure in myocardial damage in TLR4?ko mice. Conclusion The TLR4gene is involved with in heart functional injury and histopathological changes in myocardial damage following PQ poisoning in mice,which may through the regulation of TNF?αand IL?1βexpression. Our findings indi?cate that TLR4 plays an important role in mediating myocardial injury due to PQ.