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| Correlation study between autophagy of brain cells in rats with carbon monoxide poisoning and delayed encephalopathy |
| Zhang De-xin, Zhan Jie, Wang Xiao-xia, Lv Xin-peng, Deng Ying |
| Department of Emergency, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China |
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Abstract Objective To investigate the correlation between autophagy and delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods Rats with carbon monoxide poisoning were randomly divided into control group, autophagy antagonist (3-MA) group and autophagy inducer (rapamycin, Rapa) group. After 14 days, the rats were divided into delayed encephalopathy group and non-delayed encephalopathy group. To observe the number of rats with delayed encephalopathy in each group, HE staining, electron microscopy, flow cytometry and Western blotting were used to compare and analyze the brain cells of rats. Results There were 9, 12, 4 rats developed delayed encephalopathy in control group, autophagy antagonist group and autophagy inducer group, respectively. Neuronal degeneration and necrosis were shown in hippocampus of rats with delayed encephalopathy. Mild injury was shown in rats with non-delayed encephalopathy. The rate of apoptosis in delayed encephalopathy group was higher than that in non-delayed group ［(6.1±0.7)% vs.(1.6±0.2)%, P=0.018］. In the delayed encephalopathy group, the rate of apoptosis in 3-MA group was higher than that in control group ［(19.6±2.8)% vs.(6.3±0.7)%,P=0.013］; the rate of apoptosis in rapamycin group was lower than that in control group ［(2.3±0.4)% vs.(6.3±0.7)% (P=0.033). The levels of LC3-Ⅱ, beclin-1, bcl-2 in the delayed encephalopathy group were (2.37±0.25, 1.17±0.19, 1.10±0.25), respectively, which were lower than those in the non-delayed encephalopathy group (P=0.006,0.019,0.022), the level of bax was (4.80±0.29), which was higher than that of non-delayed encephalopathy (P=0.022). In the delayed encephalopathy group, the levels of LC3-Ⅱ, beclin-1, bcl-2 in 3-MA group were (1.10±0.14), (0.40±0.08),(0.43±0.05), respectively, which were lower than those in the control group (P=0.043,0.013,0.044), the level of bax was (7.37±0.33), which was higher than that in control group (P=0.027). The level of LC3-Ⅱ, beclin-1, bcl-2 in rapamycin group was (4.53±0.53), (2.07±0.05), (2.47±0.13), which was higher than that in control group (P=0.009,0.028,0.004). The level of bax was (7.37±0.33), which was lower than that in control group (P=0.008). Conclusion Autophagy plays a protective role in the injury of rat brain cells caused by carbon monoxide, which can prevent and reduce the occurrence and development of DEACMP in rats. Inhibition of autophagy can aggravate the damage of carbon monoxide to brain cells, promote or aggravate the occurrence and development of DEACMP in rats.
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