Objective: To observe the neuroprotective effect of tanshinone II(A) (Tan II(A)) on the expression of brain tissue glial fibrillary acidic protein (GFAP) and adenosine triphosphatase (ATPase) and protein disulfide isomerase (PDI) of cerebral ischemia reperfusion (I/R) injury of different time in rats, and investigate the neuroprotective and its molecular mechanism of Tan II(A) on brain injury.
Methods: Sixty-four male Sprague-Dawley rats were randomly devided into eight groups (n = 8 per group): Group 1, sham-operated animals without I/R; Group 2, animals with I/R of 3 days; Group 3, animals with I/R of 7 days; Group 4, animals with I/R of 7 days and treatment with low doses of Tan II(A); Group 5, animals with IR of 7 days, treated with high doses of Tan II(A); Group 6, animals with I/R of 15 days; Group 7, animals with IR of 15 days and low doses of Tan II(A) treatment; Group 8, animals with I/R of 15 days, treated with high doses of Tan II(A). The model of focal middle cerebral artery occlusion (MCAO) was established by suture-occluded method. After Tan II(A) treatment, pathological changes of brain tissue in all groups were observed by hematoxylin-eosin staining (HE) and the expression levels of GFAP, ATP and PDI by immunohistochemistry staining.
Results: (1) The pathological changes of ischemic injury in low and high dose of Tan II(A) treatment groups were lighter than those in I/R groups, and so were in high dose of Tan II(A) treatment group than in low dose Tan II(A) treatment group. (2) Compared with sham-operated group, expression levels of GFAP in the three different I/R groups increased evidently, while the levels in high dose of Tan II(A) treatment groups were relatively low (P < 0.05). There was no statistically difference between high dose of Tan II(A) treatment group and low dose of Tan II(A) treatment group in either 7 or 15 days treatment groups (P > 0.05). (3) Compared with sham-operated group, expression levels of ATPase and PDI in the three different I/R groups all decreased clearly; Compared with I/R groups, expression levels of ATPase and PDI in Tan II(A) treatment groups increased in the ischemic territory obviously (P < 0.05).
Conclusions: Tan II(A) may have a neuroprotective effect on ischemia-reperfusion injury by inhibiting the production of GFAP to reduce the excessive inflammatory response produced by glial cells in brain and up-regulating the activities of ATPase and PDI in neurons to improve the balance of energy metabolism and maintain the intracellular homeostasis.