ABSTRACT
Objective To investigate the effect of Xingnao Jieyu Decoction on the function of Notch/Hes signaling pathway in hippocampus of rats with post-stroke depression (PSD).Methods A total of 80 healthy male specific pathogen-free Wistar rats were randomly divided into control group,model group,prozac group and Xingnao Jieyu Decoction group;20 rats in each group.The rats in the model group,prozac group and Xingnao Jieyu Decoction group were used to prepare the cerebral ischemia model by middle cerebral artery occlusion method,and then the rats were used to prepare the depressive model by a variety of chronic unpredictable stimuli.The rats in the control group did not have any intervention.After the preparation of PSD model,the rats in the control group and model group were given saline 2.5 mL by intragastric administration,the rats in prozac group were given prozac 2.5 mL (1.8 mg · kg-1) by intragastric administration,the rats in Xingnao Jieyu Decoction group were given Xingnao Jieyu Decoction 2.5 mL (150.0 mg · kg-1) by intragastric administration;one times daily for 28 days.Ten rats in each group were sacrificed immediately on the nineteenth and twenty-eighth day of drug intervention,and the hippocampus tissues were isolated.The expression of Notch and Hes mRNA and protein in hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot method.The open probability,current amplitude,opening time and closing time of Notch signaling pathway were detected by patch clamp technique.Results On the nineteenth and twenty-eighth day of drug intervention,the expression of Notch and Hes protein and mRNA in hippocampus of rats in the model group,prozac group and Xingnao Jieyu Decoction group was significantly higher than that in the control group (P ＜ 0.05);the expression of Notch and Hes protein and mRNA in hippocampus of rats in the prozac group and Xingnao Jieyu Decoction group was significantly higher than that in the model group (P ＜ 0.05);the expressions of Notch and Hes protein and mRNA in hippocampus of rats in the Xingnao Jieyu Decoction group was significantly higher than that in the prozac group (P ＜ 0.05).There was no significant difference in Notch and Hes protein and mRNA expression in hippocampus of rats between the nineteenth and twenty-eighth day of drug intervention (P ＞ 0.05).The expression of Notch and Hes protein and mRNA in hippocampus of rats on the twenty-eighth day was significantly higher than that on the nineteenth day in the model group,prozac group and Xingnao Jieyu Decoction group (P ＜ 0.05).Compared with the control group,the open probability and current amplitude of Notch signaling pathway in hippocampus of rats increased significantly,the opening time prolonged significantly,and the closing time shortened significantly in the model group,prozac group and Xingnao Jieyu Decoction group on the nineteenth and twenty-eighth day of drug intervention (P ＜ 0.05).Compared with the model group,the open probability and current amplitude of Notch signaling pathway in hippocampus of rats increased significantly,the opening time prolonged significantly,and the closing time shortened significantly in the prozac group and Xingnao Jieyu Decoction group on the nineteenth and twenty-eighth day of drug intervention (P ＜ 0.05).Compared with the prozac group,the open probability and current amplitude of Notch signaling pathway in hippocampus of rats increased significantly,the opening time prolonged significantly,and the closing time shortened significantly in the Xingnao Jieyu Decoction group on the nineteenth and twenty-eighth day of drug intervention (P ＜ 0.05).There was no significant difference in the open probability,current amplitude,opening time and closing time of Notch signaling pathway between the nineteenth and twenty-eighth day of drug intervention in the control group(P ＞ 0.05).Compared with the nineteenth day of drug intervention,the open probability and current amplitude of Notch signaling pathway in hippocampus of rats increased significantly,the opening time prolonged significantly,and the closing time shortened significantly on the twenty-eighth day of drug intervention in the model group,prozac group and Xingnao Jieyu Decoction group (P ＜ 0.05).Conclusion Xingnao Jieyu Decoction can mediate the activation of Notch / Hes signaling pathway in hippocanpus of PSD rats,thus effectively promote the recovery of neurological function.Notch/Hes signaling pathway is expected to be an important target for drug action.
ABSTRACT
Objective To measure expressions of nicastrin and its downstream Notch-HES signaling pathwayassociated proteins in skin lesions of patients with acne inversa harbouring nicastrin gene mutations.Methods An immunohistochemical study was performed to measure the expressions of nicastrin and Notch-HES signaling pathwayassociated proteins in paraffin-embeded skin samples from lesions of 4 patients with acne inversa and confirmed nicastrin mutations and from normal skin of 6 human controls.Spearman correlation analysis was carried out to assess the relationship between the expressions of nicastrin and Notch-HES signaling pathway-associated proteins.Results In normal control skin samples,nicastrin was widely distributed in the full-thickness epidermis and skin appendages such as pilosebaceous units,apocrine glands and eccrine glands.However,the expressions of nicastrin and Notch-HES signaling pathway-associated proteins were markedly decreased in the epidermis and hair follicle infundibulum in lesions of patients harbouring nicastrin gene mutations compared with normal control skin.Furthermore,nicastrin expression was positively correlated with Notchl,Notch3 and HES-1 expressions (r =0.831,0.748 and 0.807,P ＜ 0.01,0.05 and 0.01 respectively),but not significantly correlated with Notch2 or HES-5 expressions (r =0.597,0.591 respectively,both P ＞0.05).Conclusion Nicastrin expression markedly decreases in lesions of patients with acne inversa harbouring nicastrin gene mutations,and is positively correlated with the expressions of several Notch-HES signaling pathway-associated proteins,suggesting that the decrease in nicastrin expression may take part in the pathogenesis of acne inversa by influencing the expression of the downstream Notch-HES signaling pathway.