ABSTRACT
BACKGROUND:Buyanghuanwu decoction has excel ent neuroprotective effect and can efficiently suppress nerve cel apoptosis caused by cerebral ischemia-reperfusion injury. OBJECTIVE:To investigate the effect and mechanisms of Buyanghuanwu decoction on neuronal apoptosis around hematoma in cerebral hemorrhage rats. METHODS:Seventy-two adult Sprague-Dawley rats were randomly divided into sham operation group, model group, Buyanghuanwu decoction group, and Ginkgo biloba group. Except the sham operation group, rat models of cerebral hemorrhage were established in other three groups. At 2 days after modeling, rats in the Buyanghuanwu group and Ginkgo biloba group were given Buyanghuanwu decoction 26 g/(kg?d)and Ginkgo biloba 3.5 mg/(kg?d) daily by gavage, for 14 consecutive days. Rats in the sham operation group and model group received an equal volume of saline for 14 consecutive days. After the last administration, brain tissue was obtained. TUNEL assay was utilized to detect neuronal apoptosis. Immunohistochemistry was used to detect PI3K, Akt, Bcl-2, and BAX protein expression. Wet and dry weight method was used to detect brain water content. Evans Blue assay was utilized to determine blood-brain barrier permeability. RESULTS AND CONCLUSION:(1) Compared with the sham operation group, the number of apoptotic neurons, brain water content, Evans blue content and PI3K, Akt, Bcl-2, BAX protein expression increased in the model group (P<0.05). (2) Compared with the model group, the number of apoptotic neurons, BAX protein expression, brain water content and Evans blue content were significantly reduced in the Buyanghuanwu group and Ginkgo biloba group (P<0.05), but PI3K, Akt and Bcl-2 protein expression was significantly increased (P<0.05). (3) Results suggested that Buyanghuanwu decoction inhibited neuronal apoptosis and protected brain tissue by reducing blood-brain barrier permeability, cerebral edema, and by activating PI3K/Akt signaling pathway, regulating Bcl-2 and BAX protein expression ratio.
ABSTRACT
BACKGROUND:Buyang HuanwuDecoction is commonly used in clinical medicine in treatment of intracerebral hemorrhage. Previous studies have been found that it has excelent neuroprotective effect, can efficiently inhibit the apoptosis of nervecels. Autophagic activity is closely related to apoptosis of nerve cels. CXCR4-PI3K autophagy signaling pathway has been verified in clinic. However, the effect of Buyang HuanwuDecoction is poorly understood. There is no study on Beclin-1 in the neuroprotective studies ofBuyang HuanwuDecoction. OBJECTIVE:To explore the effects ofBuyang HuanwuDecoction on CXCR4-PI3K autophagy signaling pathway and Beclin-1 in rats with cerebral hemorrhage and related mechanisms. METHODS:According to Rosenberg method, a rat model of cerebral hemorrhage was replicated and intragastricaly administeredBuyang HuanwuDecoction. Western blot assay was used to measure Beclin-1 protein. Immunohistochemical method was utilized to detect the expression of PI3K, AKT, stromal cel derived factor 1 and CXCR-4 protein. TUNEL assay was applied to identify apoptosis. RESULTS AND CONCLUSION:(1) After administration,Buyang HuanwuDecoction could reduce the number of neuronal apoptosis in rats with intracerebral hemorrhage, up-regulate the expression of Beclin-1, PI3K, AKT, stromal cel derived factor 1, and CXCR-4 protein, and exert neuroprotective effect. (2)Buyang HuanwuDecoction could activate CXCR4-PI3K autophagy signal transduction pathway, both to stimulate autophagy and to regulate autophagy state, can inhibit apoptosis, and exert cerebral protective effect.