ABSTRACT
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.
ABSTRACT
Aim: To investigate the effects of Yueju pill on depressive-like behavior and neurogenesis in chronic corticosterone (CORT) induced mice. Methods: Male C57BL/6N mice received chronic administration of CORT as well as Yueju pill. Behavioral tests were performed after the completion of treatment. The number of Ki67+ cells in the hippocampal DG region of each group was counted by immunohistochemistry test. Meanwhile, the expression levels of PKA, ERK and CREB were detected by Western blot. Results: The sucrose preference notably decreased (P < 0. 05) in CORT-induced mice in SPT, and it was raised obviously after Yueju treatment. The TST and NSF test displayed the similar results. The immunohistochemistry showed that the number of Ki67+ cells in the hippocampus DG significantly decreased in CORT-induced mice, while the number of Yueju group apparently increased (P < 0. 05). Western blot showed that compared with control group, the protein expressions of PKA-ERK-CREB pathway were down-regulated in CORT-induced mice, which were up-regulated after Yueju treatment (P < 0. 05). Conclusions: In CORT induced mice, Yueju pill can enhance the hippocampal neurogenesis by activating the PKA-ERK-CREB signaling pathway to display antidepressant-like effect.
ABSTRACT
Objective To study the interventional effects of Candesartan Cilexetil on vascular endothelial function and expres-sions of ERK/CREB signaling pathway in rats with acute myocardial infarction.Methods 30 rats were randomized into CAN group,AMI group and Sham group.Two weeks after the treatment rats were sacrificed and blood pressure,levels of blood AngⅡ, NO and NOS,endothelial vasomotor effects of isolated thoracic aorta strips,myocardial infarctual area and the expressions of ERK mRNA and CREB mRNA in infarctual myocardium were explored.Results Blood AngⅡ levels were distinctly higher in AMI group when compared with the Sham group,while the NO and NOS level were much lower.accompanied with EDDs decreased seri-ously,and higher mRNA expressions of ERK1 and CREB in infarctual myocardium.All of the above differences were significant. After the treatment of Candesartan Cilexetil,levels of serum NO and activities of NOS were obviously higher and almost reached the similar levels to those in Sham group,additionally endothelium-dependent diastole in isolated aortic strips improved greatly.Mean-while Candesartan Cilexetil can not only increase the plasma AngⅡ,but also decrease the size of myocardial infarction and the mR-NA expressions of ERK1 and CREB in infarctual myocardium significantly.However,blood pressure in all groups was not affected. Conclusion Candesartan Cilexetil can greatly improve the disordered endothelial function developing post-AMI,decrease the size of myocardial infarction and down-regulate the mRNA expressions of ERK and CREB in myocardium of infarctual zone.And all of the above protective effects of Candesartan Cilexetil were independent on blood pressure lowering.