补肾开窍祛痰方治疗缺氧缺血性脑损伤脑瘫的分子机制研究OACHSSCD

Objective:To investigate the molecular mechanisms of Bushen Kaiqiao Qutan Formula(BSKQQTF)in treating a rat model of cerebral palsy induced by hypoxic-ischemic brain damage(HIBD).Methods:Rats were randomly divided into a normal group,a sham operation group,and a modeling group.The HIBD cerebral palsy model was established using the modified Rice-Van-nucci method.Successfully modeled rats were further randomly assigned to a model group,a Liuwei Dihuang Decoction group,and low-,medium-,and high-dose BSKQQTF groups.The drug intervention groups received intragastric administration starting on the second day after surgery,while the normal,sham operation,and model groups were administered an equal volume of normal saline for three consecutive weeks.Neurological function scores were evaluated at 1,2,and 3 weeks after modeling.The expression levels of Cytochrome C(Cyt-C),Caspase-9,Caspase-3,and apoptotic protease activating factor-1(Apaf-1)in the hippocampal CA1 region were assessed in each group.Results:Zea-Longa scores:Compared with the model group,the normal,sham operation,BSKQQTF(low-,medium-,and high-dose),and Liuwei Dihuang Decoction groups showed significantly decreased Zea-Longa scores at weeks 1 and 2(P＜0.05).Immunohistochemistry:Compared with the model group,positive expression of Cyt-C,Caspase-9,Caspase-3,and Apaf-1 proteins in the hippocampal CA1 region was reduced in the normal,sham operation,and medium-dose BSKQQTF groups.Western blot for hippocampal CAI region:Compared with the model group,protein expression levels of Cyt-C,Caspase-9,Caspase-3,and Apaf-1 were decreased in the medium-dose BSKQQTF group(P＜0.01).In the high-dose BSKQQTF and Liuwei Dihuang Decoction groups,Apaf-1 protein expression was also decreased(P＜0.01).Real-time quantitative PCR(qRT-PCR):Compared with the model group,mRNA expression levels of Cyt-C,Caspase-9,Caspase-3,and Apaf-1 in the hippocampal CA1 region were significantly reduced in the medium-dose BSKQQTF group(P＜0.01).Conclusion:BSKQQTF can treat HIBD-induced cerebral palsy,possibly by inhibiting neuronal apoptosis through suppression of activation of the Cyt-c/Caspase signaling pathway.