1.Study on Improvement Effects of Icariin on Cognitive Function in Schizophrenia Model Rats and Its Mechanism
Yunqin LIU ; Yanqin LIU ; Hanbin JI ; Wenhao XIAO ; Li LIN
China Pharmacy 2021;32(7):812-818
OBJECTIVE:To study the improvement effects of ica riin(ICA)on cognitive function in schizophrenia model rats and its mechanism. METHODS :SD rats were divided into blank control group ,model group ,ICA low-dose ,medium-dose and high-dose groups (15,30,60 mg/kg). Except for blank control group ,other groups were given N-methyl-D-aspartate receptor antagonist MK- 801(0.2 mg/kg)intraperitoneally to induce schizophrenia rats models ,once a day ,for consecutive 14 days. After modeling,ICA groups were intragastrically administered with the corresponding drugs ,while blank control group and model group were intragastrically administered with the same volume of water ,once a day ,for consecutive 7 days. The behavioral com changes of rats were detected by Morris water maze test ,open field test , forced swimming test and Y maze test pathological changes of hippocampus were observed by Nissl staining;the levels of cholinergic indexes [acetylcholine (Ach),choline acetyltransferase (ChAT) and acetylcholinesterase (AchE)] in cerebral tissues were detected by ELISA. The expression of BDNF ,ERK and CREB mRNA in cerebral tissue were detected by RT-PCR ;expression or phosphorylation level of BDNF ,ERK,CREB protein ,apoptosis related proteins (Bcl-2,Bax and Caspase- 3)were detected by Western blot. RESULTS :Compared with blank control group ,escape latency ,distance at T 1-T3, cumulative immobility time and the expression of Caspase- 3 protein in cerebral tissues were significantly increased in model group (P<0.05);the times of crossing platform ,alternation rate ,the number of Nissl staining positive neurons in hippocampus tissues , the levels of Ach and ChAT in cerebral tissues ,Bcl-2/Bax ratio ,mRNA and protein expression of BDNF ,mRNA expression of ERK and CREB ,the phosphorylation of ERK 1/2 and CREB were significantly decreased (P<0.05).Compared with model group , escape latency ,distance at T 1-T3,cumulative immobility time ,the number of Nissl staining positive neurons ,AchE level in cerebral tissues and relative expression of Caspase- 3 protein were significantly decreased in ICA high-dose group (P<0.05);the times of crossing platform ,alternation rate ,levels of Ach and ChAT in cerebral tissues ,Bcl-2/Bax ratio ,mRNA and protein expression of BDNF ,mRNA expression of ERK and CREB ,the phosphorylation of ERK 1/2 and CREB were increased significantly(P<0.05). Above indexes in ICA low-dose and medium-dose groups were partially improved significantly than model group(P<0.05). CONCLUSIONS :ICA can improve cognitive function in schizophrenia model rats.Its mechanism may be related to regulating cholinergic system ,inhibiting neuronal apoptosis ,and promoting the expression of BDNF/ERK/CREB signaling pathway.