摘要
目的观察3β-双水杨酰薯蓣皂苷元对局灶性脑缺血/再灌注损伤大鼠的损伤保护作用及机制。方法♂SD大鼠120只,随机分为假手术组、缺血/再灌注组、3β-双水杨酰薯蓣皂苷元低(25 mg·kg-1)、中(50 mg·kg-1)、高(100mg·kg-1)剂量组和尼莫地平(20 mg·kg-1)组,参照改良的线栓法,建立大鼠大脑中动脉栓塞(middle cerebral antery occlusion,MCAO)模型,脑缺血2 h后再灌注24 h,行神经功能症状评分,断头处死大鼠,TTC染色后,利用图像分析软件Image J(ver1.37c NIH)测定脑梗死面积和脑梗死体积,采用HE染色、Nissl染色用于组织学观察、凋亡细胞检测及免疫荧光检测,并采用Western blot法检测PI3K/Akt信号通路相关蛋白表达。结果薯蓣皂苷元各组相对于模型组,神经功能缺损及梗死体积均明显减少(P<0.05或P<0.01),并呈剂量依赖性。其中高剂量组神经功能评分及梗死体积与尼莫地平组相似(P>0.05)。薯蓣皂苷元能减轻MCAO大鼠的氧化应激水平,降低MDA及MPO水平,并呈剂量依赖性。尼莫地平对大鼠MCAO氧化应激水平无影响。薯蓣皂苷元可诱导P-Akt蛋白的表达,增加Bcl-2蛋白的表达,降低Bax及Caspase-3蛋白的表达,激活PI3K/Akt信号通路,降低细胞凋亡水平。另外,薯蓣皂苷元诱导Nrf2及NQO1的蛋白表达(P<0.05),降低MCAO氧化应激水平。结论薯蓣皂苷元具有抗脑缺血/再灌注引起的脑损伤,其机制可能与激活PI3K/Akt途径、调控凋亡相关基因及抗氧化基因有关。
Aim To study and explore the neuroprotec- tive effects of 3 β- Double Salicyloyl Diosgenin （DDS） on focal cerebral isehemia / reperfusion （I/R） injury in rats and its mechanism. Methods A total of 120 male SD rats were randomly divided into 6 groups： sham-operated group , I/R group , I/R group ＋ Nimo- dipine group, I/R ＋ high dose DDS group,I/R ＋ mid- dle dose DDS group,I/R ＋ low dose DDS group. Cer- ebral ischemia-reperfusion model in rats was estab- lished by improved Suture-occluded method. Infarct volume was tested by Trc colouration. Cell apoptosis was detected by HE and Nissl colouration. PI3K/Akt signal pathway related proteins were detected by West- ern blot. Results Neurologic stroke score and infarct volume of DDS high dose group was inferior to those ofthe model group （ P 〈 0.05 ）. and the effect was dose- dependent. However, these indexes were similar to those of nimodipine group. Oxidative stress level of MCAO rats was decreased by DDS. The MDA and MPO level of DDS group was lower than that the model group because of the suppression on Nrf2 and NQO1 protein expression（ P 〈 0. 05 ）, and the effect was dose- dependent. Conclusion DDS can decrease the apoptotic level because of inducing P-Akt and Bcl-2 protein expres- sion and suppressing Bax and Caspase-3 protein expres- sion. （ P 〈 0. 05 ）
出处
《中国药理学通报》
CAS
CSCD
北大核心
2013年第12期1672-1675,共4页
Chinese Pharmacological Bulletin
基金
国家"重大新药创制"科技重大专项资助项目(No 2009ZX0901-007)
