百草枯中毒致大鼠急性肺损伤时NF-κB抑制剂对中性粒细胞凋亡的影响

目的:探讨在百草枯(PQ)中毒所致大鼠急性肺损伤时NF-κB抑制剂(PDTC)对中性粒细胞凋亡的影响。方法:120只大鼠随机分为4组:1正常对照组(C组):腹腔注射生理盐水3ml/kg;2PDTC对照组(PC组):腹腔注射PDTC120mg/kg,半小时后腹腔注射生理盐水3ml/kg;3急性肺损伤组(L组):大鼠腹腔注射2%PQ(25mg/kg);4急性肺损伤+PDTC干预组(L+P组):腹腔注射PDTC(120mg/kg),半小时后腹腔注射2%PQ。后两组分别以腹腔注射PQ后的1d、3d、5d作为观测点,处死动物、取材,每个时间点16只大鼠。取肺组织HE染色来评价肺组织损伤情况;检测血清中TNF-α水平、肺泡灌洗液中PMN的NF-κBp65表达、PMN中胞浆蛋白IκBα的含量和中性粒细胞凋亡率。结果:肺组织病理结果显示,C组和PC组大鼠的肺组织结构基本完整。L组炎性细胞浸润明显增多,肺组织损伤程度加重。P+L组肺组织损伤程度较轻。L组血清TNF-α水平较C组显著增加,P+L组降低。L组3d时PMN的凋亡率最低(3.52±0.34)%,P+L干预组与相应时间点L各组相比凋亡率均增加。结论:百草枯中毒导致了大鼠急性肺损伤,在预先应用NF-κB抑制剂(PDTC)后,使延缓的中性粒细胞凋亡恢复正常,从而有效地减轻了百草枯中毒所致的κB大鼠急性肺损伤。

Effects of NF-κB inhibitor on PMN apoptosis in lung injury associated with paraquat poisoning of rats

Objective:To investigate the effects of NF-κB inhibitor(PDTC) on PMN apoptosis in lung injury associated with paraquat poisoning of rats. Methods:120 Rats were randomly divided into four groups:C group (NS 3ml/kg,ip),PC group (PDTC120mg/kg,ip and after half an hour NS 3ml/kg,ip),L group ( 2% PQ 25mg/kg,ip),P+L group (PDTC120mg/kg,ip and after half an hour 2% PQ 25mg/kg,ip). L group and P+L group were divided into 1d、3d、5d sub group further,each group had 16 rats. Used optical microscope to observe the pathologic change of lungs.The level of TNF-α in serum was detected. The expression of NF-κB P65 in PMN of BALF was determined. The content of IκB α of cytoplasm protein was determined.The ratio of PMN apoptosis was assaied.Results:The degree lung injury in L group was higher than that in C group and PC group. But in P+L group the degree of lung injury was lighter.The content of TNF-α in L group was higher than that in P+L group. The ratio of PMN apoptosis in L group was lowest(3.52±0.34%).The ratio of PMN apoptosis in P+L group raised. Conclusion:Paraquat poisoning leads to acute lung injury in rats.After using of NF-κB inhibitor(PDTC),the process of PMN apoptosis regained normal and the lung injury associated with paraquat poisoning getslighter.