Objective To investigate the effect of tanshinone IIA (TSA) on the protein expression of
phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) and
transducers of regulated CREB1 (TORC1) and volume of cerebral infarction in rats' parietal cortex
during focal cerebral ischemia.
Methods Male Sprague-Dawley rats were randomly divided into sham group, control group, TSA
low dose group and TSA high dose group, twelve in each group. Focal cerebral ischemia model
was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.
The rats were scored after waking up. 2, 3, 4 or 5 scores were brought into this study. TSA solution
(10 mg/kg, TSA-L; or 20 mg/kg, TSA-H) was injected intraperitoneally immediately after the rats
waked up. The rats were scored and sacrified at 24 h after waking up. Infarct size was analyzed
with 2, 3, 5-triphenyltetrazolium chloride (TTC). Western blotting was used to analyze the protein
expression of TORC1 and p-CREB of each group in the nerve cell, and the positive products were
analyzed by image analysis system.
Results Compared with control group, the infarct size of TSA-H group was significantly decreased
(P =0.004). And nuclear accumulation of TORC1 was only significantly increased in TSA-H group (P <0.001). Compared with control group, the decrease of the infarct size in TSA-L group and
the increase of nuclear protein expression of TORC1 have no remarkable differences (P =0.148,
P =0.083, respectively), the expression of TORC1 (Total) and p-CREB (Nucleus) protein level in
TSA-H (P <0.001) and TSA-L ((P =0.002, P =0.001) group was significantly increased, the enhanced
TORC1 is localized in the nucleus and cytoplasm of neurons.
Conclusion TSA could protect rat brain from ischemic damage and upregulate the expression of
TORC1-CREB pathway in rats' parietal cortex during focal cerebral ischemia.
