ABSTRACT
Objective To investigate the therapeutic effect and mechanism of total flavone of haw-thorn leaf ( TFHL) on p38MAPK signaling pathway and inflammation factors in rats brain with chronic cere-bral ischemia.Methods SPF class healthy male SD rats were randomly divided into sham group, model group,TFHL group and Ginkgo leaf group( 12 rats in each group) .Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model.Morris water maze method was used to evaluate learn-ing and memory abilities of rats.Immunohistochemistry and Western blot methods were used to measure the expression of caspase-3 and p38MAPK proteins.ELISA method was used to measure the amounts of TNF-αand IL-1βin hippocampal tissue.Results Compared with the model group,TFHL treatment (36 d) can im-prove learning and memory capabilities of vascular dementia rats,shorten the escape latency ( TFHL group(10.01±2.85) s vs Model group (19.54±6.12) s, P<0.05) and the course of searching platform(TFHL group(2.6044±0.3219)m vs model group(3.3502±0.6231)m, P<0.05),increase the numbers of crossing the platform (TFHL group(5.17±2.12) times vs Model group (3.96±1.34) time,s P<0.05) and the platform quadrant swimming distance percentage (TFHL group(48.22±7.39)%vs model group (33.42±5.32) %, P<0.01).The number of caspase-3 positive cells in the hippocampus significantly reduced (TFHL group(1.677 ±0.164) vs Model group (2.387±0.171), P<0.05),the expression level of P38MAPK protein (TFHL group (0.0161±0.0003) vs Model group (0.0254±0.0018), P<0.05),TNF-α(TFHL group(19.61±3.61) ng/10 mg vs Model group (27.82±6.57) ng/10 mg, P<0.01)and IL-1β(TFHL group(24.41±2.56) ng/10 mg vs Model group (29.43±5.26) ng/10 mg, P<0.05) were significantly decreased.Conclusion TFHL plays a protective role in nerve function of the chronic cerebral ischemia rats.The mechanism of its antia-poptosis might be associated with the activation of P 38MAPK signaling pathway,inflammation and the apoptosis of neurons in the brain.
ABSTRACT
CCAAT enhancer binding protein A (CEBPA) and its product transcription factor CCAAT enhancer binding protein α (C/EBPα) play pivotal roles in early granulocyte development. C/EBPα induces the transition and keeps the balance of differentiation and proliferation of myeloid progenitors. The mutation and dysregulation of CEBPA at transcription, translation or post-translation level lead to differentiation block and over proliferation of immature hematopoietic cells, which are important mechanisms of acute myeloid leukemia (AML). The mutation and dysregulation of CEBPA also provide clues for evaluating the outcome of AML patients and potential targets for differentiation-inducing therapies. This review focus on CEBPA mutation and AML, dysregulation of C/EBPα protein expression and AML, as well as C/EBPα protein and targeting therapy.