Protective effect of emodin on brain injury induced by intrauterine inflammation in premature birth rats by regulating HMGB1/NF-κB signaling pathway
Objective To explore the protective mechanism of emodin on brain injury in premature birth rats induced by intrauterine inflammation by regulating high-mobility group protein B1(HMGB1)/nuclear transcription factor-κB(NF-κB)signaling pathway.Methods Pregnant rats were injected intraperitoneally with lipopolysaccharide to establish the model of premature birth induced by intrauterine inflammation.They were randomly divided into model group,low dose emodin(25 mg/kg)group,high dose emodin(50 mg/kg)group,empty plasmid group,and high dose emodin(50 mg/kg)+HMGB1 overexpression group,with 10 rats in each group,10 pregnant rats were injected with an equal dose of physiological saline intraperitoneally as the control group,10 offspring rats of pregnant rats in each group were randomly selected,after treatment with emodin and plasmid,the number of live births and birth weight of offspring of pregnant rats in each group were measured.The pathological morphological changes of uterus and placenta were detected by H-E staining.The slope experiment and cyl-inder experiment were used to test the neuroethology ability of offspring rats in each group.TUNEL staining was used to de-tect neuronal apoptosis in the hippocampus and cerebral cortex of offspring rats in each group;enzyme linked immunosorbent assay(ELISA)was used to determine the levels of pro-inflammatory factor cyclooxygenase-2(COX-2)and interleukin-6(IL-6)in the brain tissue and serum of the offspring in each group.Western blot was used to detect the expression of HMGB1/NF-κB pathway proteins in the brain tissues of offspring rats in each group.Results Compared with the control group,the pathologi-cal scores of uterus and placenta,the time of turning head,the apoptosis rate of neurons in hippocampus and cerebral cortex,the levels of COX-2 and IL-6 in brain tissue and serum,the expression of HMGB1 protein in brain tissue,and p-NF-κB p65/NF-κB p65 in the model group increased(P＜0.05),the number of live births,birth weight of offspring,and the number of times of touching the barrel wall decreased(P＜0.05).Compared with the model group,the pathological scores of uterus and placenta,the time of turning head,the apoptosis rate of neurons in hippocampus and cerebral cortex,the levels of COX-2 and IL-6 in brain tissue and serum,the expression of HMGB1 protein in brain tissue,and p-NF-κB p65/NF-κB p65 in the low-dose and high-dose emodin groups decreased(P＜0.05),the number of live births,birth weight of offspring,and the number of times of touching the barrel wall all increased(P＜0.05).Overexpression of HMGB1 could weaken the amelioration effect of high dose emodin on uterine and placental injury and premature birth symptoms of preterm pregnant rats caused by intrauterine inflammation,and antagonistic its brain protective effect on offspring rats.Conclusion Emodin can reduce the production of proinflammatory factors by inhibiting the activation of HMGB1/NF-κB signal,alleviating the damage of uterus and placenta in pregnant rats,improving the neurobehavioral ability of offspring rats and alleviating their brain damage.
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