PI3K/Akt pathway contributes to neuroprotective effect of Tongxinluo against focal cerebral ischemia and reperfusion injury in rats.

摘要: Abstract Ethnopharmacological relevance Tongxinluo (TXL), a compound prescription, is formulated according to the collateral disease doctrine of traditional Chinese medicine, and widely used for treatment cardio-cerebrovascular diseases in China. Aim study We aimed investigate neuroprotective effect TXL on focal cerebral ischemia reperfusion injury rats by attenuating its brain damage neuronal apoptosis, assess potential role phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway this protection. Materials methods Adult Male Sprague-Dawley ( n =120) were randomly divided into 5 groups: sham, (I/R), plus (1.6 g/kg/day) (TXL1.6), TXL1.6 LY294002 dimethyl sulfoxide (DMSO) (TXL1.6+LY294002), DMSO (TXL1.6+vehicle). Prior grouping, was selected be optimal dose evaluating neurological deficits score five group (Sham, I/R, TXL0.4, TXL0.8 TXL1.6, =30) at 0, 1, 3, 5, 7 days after reperfusion. Rats, being subjected middle artery occlusion (MCAO) 90 min followed 24 h reperfusion, ischemia/reperfusion models. At infarct area measured via tetrazolium staining showed Nissl staining. The double Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) immunofluorescence with NeuN, performed evaluate apoptosis. Proteins involved PI3K/Akt detected Western blot. Results results that markedly improved function, reduced area, decreased damage, significantly attenuated while these effects eliminated inhibition LY294002. also found up-regulated expression levels p-PDK1, p-Akt, p-c-Raf, p-BAD down-regulated Cleaved caspase 3 notably, which partially reversed Additionally, increment p-PTEN level had little response treatment. Conclusions These findings demonstrated provided neuroprotection against mediated partly activation pathway.