Study on Regulatory Mechanism of Huangqi Decoction on Bcl-2/NF-κB Signal Pathway in Rats with Brain Injury Induced by 12C6+ Ion Radiation
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Graphical Abstract
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Abstract
OBJECTIVE To observe the effect of Huangqi decoction on expression of B-cell lymphoma-2(Bcl-2) and nuclear-factor-κB(NF-κB) of brain tissue in model rats with brain injury induced by 12C6+ ion radiation, and to further reveal its mechanism. METHODS Fifty SPF Wistar rats were randomly divided into five groups:normal control group, radiation alone model group, Huangqi decoction high-dose, middle-dose and low-dose group(18, 9, 4.5 g·kg-1·d-1). Rats in the Huangqi decoction high-dose, middle-dose and low-dose groups were given Huangqi decoction by gavage for two weeks. At day 8 of gavage, the brain of the rats of the radiation alone model group and the the Huangqi decoction high-dose, middle-dose and low-dose groups were radiated once by 4 Gy 12C6+ ion. The normal control group was not radiated. After radiation for 7 d, all groups of rats were executed. The pathomorphism changes of brain tissue were observed by HE, the gene and protein expression of Bcl-2, Bax and caspase-3 in brain tissue was assessed by RT-PCR and immunohistochemical stain, and expression of NF-κB protein in brain tissue was analyzed by Western blotting. RESULTS Compared with the normal control group, the body weight and brain coefficient significantly decreased, the gene and protein expression of Bcl-2 in brain tissue significantly decreased, the gene and protein expression of Bax, caspase-3 in brain tissue significantly raised, and the protein expression of NF-κB in the brain tissue significantly increased in the radiation alone model group(P<0.05), the number of nerve cells reduced at different degrees, loose arrangement, nuclear pyknosis and deep dyeing, widened gap around nerve cells in radiation alone model group. Compared with the radiation alone model group, the brain coefficient and the protein expression of Bcl-2 in brain tissue raised obviously in Huangqi decoction middle-dose, high-dose group, the body weight and the gene expression of Bcl-2 in brain tissue increased significantly in high-dose group(P<0.05). But, the protein expression of NF-κB declined obviously in Huangqi decoction intervention groups, the gene and protein expression of caspase-3 decreased significantly in Huangqi decoction middle-dose, high-dose group, the gene and protein expression of Bax decreased significantly in Huangqi decoction high-dose group(P<0.05), the nerve cells reduction and loose arrangement in Huangqi high-dose decoction group were relieved significantly. CONCLUSION Huangqi decoction has protective effect on 12C6+ ion radiation induced mice brain injuries, the mechanism may be related to the reduction of neuron apoptosis which was the up-regulation of Bcl-2 protein, down-regulation of Bax, caspase-3 and NF-κB by Bcl-2/NF-κB signal pathway.
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