Objective To analyze the effect of adrenocorticotropic hormone(ACTH) on the expression of stress proteins in infantile spasm model induced by N-methyl-D-aspartate(NMDA), in order to provide theoretical evidence for the treatment of infantile spasm. Methods Totally 60 neonatal rats were randomly divided into control group, NMDA group and ACTH group, with 20 rats in each group. On the 11th day of birth, ACTH group was injected with 10 mg/(kg·d) ACTH intraperitoneally, and the other two groups were injected with the same amount of saline. On the 15th day of birth, 15 mg/(kg·d) NMDA was intraperitoneally injected into NMDA group and ACTH group, and the same amount of saline was injected into control group. Spasticity score was used to score the spasticity symptoms of three groups. The mRNA transcription levels of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and ACTH in hippocampus were measured by q-PCR. The expressions of corticotropin releasing hormone (CRH) and corticotropin releasing hormone type 1 receptor (CRHR1) in hippocampus were measured by Western Blot method. Results The score of spasticity in NMDA group was significantly higher than that in control group (t=11.236, P<0.001). The score of spasmodic symptoms in ACTH group was lower than that in NMDA group (t=-6.347, P<0.001). Compared with the control group, the transcription levels of IL-1β and IL-6 in the hippocampus of NMDA group increased (IL-1β:t=6.237, P<0.001; IL-6: t=6.553, P<0.001). The transcriptional levels of IL-1βand IL-6 in the hippocampus of ACTH group were lower than those of NMDA group (IL-1β: t=-7.669, P<0.001; IL-6: t=-8.125, P<0.001). The transcription level of ACTH mRNA in hippocampus of group ACTH was higher than that of NMDA group (t=7.758, P<0.001). Compared with the control group, the expression levels of CRH and CRHR1 protein in hippocampus of NMDA group were up-regulated (CRH: t=7.517, P<0.001; CRHR1: t=7.745, P<0.001). While the expression of CRH and CRHR1 protein in ACTH group was lower than that in NMDA group (CRH: t=-6.120,P=0.003; CRHR 1: t=-6.050, P=0.005 ). Conclusions ACTH could relieve spasm symptom induced by NMDA in neonatal rats. It is speculated that ACTH may help decrease the mRNA expressions of IL-1β and IL-6 in the hippocampal tissues of neonatal rats, up-regulate the mRNA expression of ACTH, and inhibit the protein expressions of CRH and CRHR1.
Key words
adrenocorticotropic hormone /
N-methyl-D-aspartate /
infantile spasticity /
stress protein
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