"标本配穴"针刺法联合盐酸舍曲林调节神经递质治疗抑郁小鼠机制研究OA

Obj ective To investigate the improving effect of"syndrome-essence acupoint compatibility"acupuncture combined with sertraline hydrochloride on depression-like behaviors and hypothalamic neural function in mice induced by chronic unpredictable mild stress(CUMS),evaluate the advantages of synergistic acupuncture-medicine intervention,and provide a certain modern neurobiological basis for the traditional Chinese medicine(TCM)theory of treating both manifestation and root cause.Methods Thirty healthy ICR mice(half male and half female)were randomly divided into 5 groups:blank group,model group,sertraline hydrochloride intervention group,"syndrome-essence acupoint compatibility"acupuncture intervention group,and"syndrome-essence acupoint compatibility"acupuncture combined with sertraline hydrochloride intervention group,with 6 mice in each group.Except for the blank group,mice in the other groups were subjected to CUMS modeling,and the intervention lasted for 21 days.For behavioral assessment,forced swimming test and open field test were used to evaluate depression-like and anxiety-like behaviors in mice.For molecular indicators,the contents and ratio of γ-aminobutyric acid(GABA)and glutamate(Glu)in the hypothalamus were detected by HPLC-MS/MS;serum levels of 5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NA)were measured by ELISA method;the protein expressions of GRN2B,GRM5,VGLUT1,GABAAR and GABABR were detected by Western blot method.Histopathological changes and neural activity were analyzed by H&E staining and FosB immunohistochemistry.Results(1)Behavioral improvement.CUMS modeling significantly induced depression like behavior in mice,manifested as prolonged swimming immobility time in forced swimming experiments and decreased autonomous exploration ability in open field experiments.All intervention groups showed improvement in the depression phenotype mentioned above,with the most significant effect observed in the group treated with acupoint acupuncture combined with sertraline hydrochloride intervention,and their behavioral manifestations were closest to those of the blank group.(2)Regulation of neurotransmitter levels.Compared with the blank group,the model group mice showed a significant decrease in hypothalamic GABA content,GABA/Glu ratio,and serum 5-HT,DA,and NA levels,while the hypothalamic Glu content increased.The"syndrome-essence acupoint compatibility"acupuncture combined with sertraline hydrochloride intervention can most effectively restore the balance of neurotransmitters,and its regulatory effect is superior to single acupuncture or Western medicine intervention.(3)Restoration of related protein expression.Compared with the blank group,the expression levels of GRN2B,GRM5,VGLUT1,GABAAR,and GABABR proteins in the hypothalamus of the model group were significantly downregulated.The"syndrome-essence acupoint compatibility"acupuncture combined with sertraline hydrochloride intervention group can significantly upregulate the expression levels of these proteins,and the degree of recovery is most prominent among all intervention groups,showing a significant synergistic advantage.(4)Organizational pathology and increased neural activity.Compared with the blank group,the model group showed sparse arrangement of hypothalamic neurons and damage such as cell body atrophy,while FosB expression was significantly inhibited.The"syndrome-essence acupoint compatibility"acupuncture combined with sertraline hydrochloride intervention group showed the best performance in improving pathological damage to hypothalamic tissue and inducing a rise in FosB levels,which helps to rebuild the homeostasis of hypothalamic function.Conclusion The"syndrome-essence acupoint compatibility"acupuncture combined with sertraline hydrochloride intervention can significantly improve depression like behavior in CUMS mice,restore the balance of neurotransmitter and related protein expression,upregulate FosB levels,improve hypothalamic tissue damage,demonstrate the antidepressant advantages of acupuncture and medicine synergy,and demonstrate the potential for transformation of traditional Chinese medicine's"specimen and treatment"approach in antidepressant treatment.