宣氏益智方对ADHD大鼠前额叶皮质神经递质及神经元凋亡的影响OA

AIM To investigate the effects of Xuan's Yizhi Decoction on neurotransmitters and neuronal apoptosis in the prefrontal cortex of rats with attention deficit hyperactivity disorder(ADHD).METHODS Forty 4-week-old male juvenile spontaneously hypertensive rats(SHRs)were randomly divided into model group,methylphenidate group(2 mg/kg),and low-,medium-and high-dose Xuan's Yizhi Decoction groups(7.5,15 and 30 g/kg).Age-matched male WKY rats were selected as normal control group,with 8 rats in each group.Continuous intragastric administration was performed for 35 days.The body weight and food intake of the rats in each group were recorded.The elevated plus maze test and Morris water maze test were used to evaluate hyperactivity,impulsivity,and learning and memory abilities.ELISA was employed to detect the levels of glutamic acid(Glu),norepinephrine(NE),γ-aminobutyric acid(GABA),dopamine(DA),and 5-hydroxytryptamine(5-HT)in the prefrontal cortex.Nissl staining was used to observe the changes of neurons and Nissl bodies in the prefrontal cortex.TUNEL assay was conducted to detect cellular apoptosis in the prefrontal cortex.Western blot was applied to detect the protein expressions of Bcl-2,Bax,Caspase-3,and cleaved Caspase-3 in the prefrontal cortex.RESULTS Compared with the model group,Xuan's Yizhi Decoction significantly decreased the ratios of open arm entries and time spent in open arms in the elevated plus maze test(P＜0.05).It also shortened the escape latency in the place navigation test(P＜0.05),increased the time spent in the target quadrant,swimming distance,and platform crossing times in the spatial probe test(P＜0.05).Furthermore,it increased the number of Nissl bodies(P＜0.01)and reduced cellular apoptosis in the prefrontal cortex.Additionally,the decoction elevated the levels of NE,GABA,and DA(P＜0.05,P＜0.01)and decreased the level of Glu(P＜0.01)in the prefrontal cortex.The protein expression of Bcl-2 and the Bcl-2/Bax ratio were upregulated(P＜0.05,P＜0.01),whereas the protein expressions of Bax,Caspase-3,and cleaved Caspase-3 were downregulated(P＜0.05,P＜0.01)in the prefrontal cortex.CONCLUSION Xuan's Yizhi Decoction can attenuate hyperactivity and impulsive behaviors and improve learning and memory functions in ADHD rats.Its therapeutic effect may be associated with correcting neurotransmitter imbalance in the prefrontal cortex and modulating the Bcl-2/Bax/Caspase-3 signaling pathway to enhance the anti-apoptotic capacity of prefrontal cortex neurons.