和胃安神方对失眠模型大鼠视交叉上核c-fos、c-jun及神经元型一氧化氮合酶表达的影响OA

Objective To investigate the effects of Hewei Anshen Formula on the expression of im-mediate early genes(IEGs)c-fos,c-jun,and neuronal nitric oxide synthase(nNOS)in the suprachiasmatic nucleus(SCN)of insomnia model rats.Methods Sixty male Sprague-Dawley rats were randomly allocated to six groups(n=10 per group):normal control,model control,estazolam,and Hewei Anshen Formula low-,medium-,and high-dose groups.Except for the normal control group,insomnia models were induced in all other groups via intraperitoneal injection of para-chlorophenylalanine(PCPA),with modeling efficacy validated by pentobarbital sodium-induced righting reflex test.Following successful modeling,rats received 7 consecutive days of intragastric administration:the normal control and the model control groups were administered 10 mL/kg distilled water;the estazolam group received 0.33 mg/(kg·day)estazolam aqueous solution;Hewei Anshen Formula groups were given Hewei Anshen Formula decoction at concentrations of 1 g/mL(low-dose),2 g/mL(medium-dose),and 4 g/mL(high-dose),all at 10 mL/kg volume.Upon completion of treatment,behavioral assessments were conducted using open field test(OFT)and elevated plus maze(EPM)test,while expression of c-fos/c-jun proteins and c-fos/c-jun/nNOS genes in the SCN were analyzed by immunohistochemistry(IHC)and quantitative polymerase chain reaction(qPCR),respectively.Results After model establishment,compared with the normal control group,the model groups showed significantly prolonged sleep latency(P＜0.01)and reduced total sleep time(P＜0.01).Following the final drug administration,the model control group exhibited significantly increased total distance traveled(P＜0.01)and average speed(P＜0.01)in the open field test(OFT),while displaying significantly decreased central area duration(P＜0.01)in OFT,reduced percentage of open arm entries(P＜0.01)and open arm time(P＜0.01)in the elevated plus maze(EPM),along with significantly elevated expression of c-fos/c-jun proteins and c-fos/c-jun/nNOS genes in the suprachiasmatic nucleus(SCN)(all P＜0.01).Compared with the model control group,both the estazolam group and the Hewei Anshen Formula medium/high-dose groups demonstrated significantly decreased total distance(P＜0.05 or P＜0.01)and average speed(P＜0.05 or P＜0.01)in OFT with increased central area duration(P＜0.05 or P＜0.01),whereas the estazolam group and all the Hewei Anshen Formula dose groups showed increased percentage of open arm entries(P＜0.05 or P＜0.01)and open arm time(P＜0.05 or P＜0.01)in EPM,accompanied by significantly reduced expression of c-fos/c-jun/nNOS in SCN(P＜0.05 or P＜0.01).Conclusion Hewei Anshen Formula ameliorates insomnia in rats,potentially through down-regulating the expression of c-fos,c-jun,and nNOS in the SCN.