Study on Improvement Effects of Z-guggulsterone Combined with Acetyl- 11-keto-β-boswellic Acid on Cerebral Ischemia- reperfusion Injury Model Rats / 中国药房

ABSTRACT

OBJECTIVE： To study the improvement effects of Z-guggulsterone （Z-GL） combined with acetyl-11-keto-β- boswellic acid （AKBA） on cerebral ischemia-reperfusion injury model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group， Z-GL+AKBA low-dose and high-dose groups （25， 50 mg/kg）， with 10 rats in each group. Except for sham operation group， middle cerebral artery occlusion/reperfusion injury model was induced by suture method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion； sham operation group and model groups were given constant volume of DMSO intragastrically， every 12 h， for consecutive 7 d. The neurological deficits were evaluated with modified Longa score； HE staining was performed to observe the pathological changes of cerebral tissue in rats； the area of cerebral infarction was measured by TTC， and the percentage of cerebral infarction area； TUNEL staining was performed to detect apoptotic neurons. The expression of CD34， VEGF and DLL4 were detected by immunofluoresence and immunoblotting assay， respectively. RESULTS： Compared with sham operation group， the number of cortical cells in the model group decreased and arranged irregularly， with obvious infarct area and obvious decrease of neovascularization； the neurological deficit score， the percentage of cerebral infarction area and TUNEL positive cells increased significantly， while the expression of CD34， VEGF and DLL4 decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， the above symptoms of the rats in each administration group were significantly improved， the neurological deficit score， the percentage of cerebral infarction area and the number of TUNEL positive cells were significantly reduced； the expression levels of CD34， VEGF and DLL4 were significantly increased； the neurological deficit score， the percentage of cerebral infarction area and the number of TUNEL positive cells in Z-GL+AKBA high-dose group were significantly lower or less than low dose group； the expression of CD34 and DLL4 in high-dose group was significantly higher than low-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Z-GL combined with AKBA can relieve neurological deficit and cerebral injury of cerebral ischemia-reperfusion injury model rats， which may be related to promoting angiogenesis and up-regulating the expression of VEGF and DLL4 protein， with a certain dose-dependent effect.