Shexiang Tongxin Dropping Pill () Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation

Objective: To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STDP) following sodium laurate-induced coronary microembolization (CME) in rats.

Methods: Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg·kg^-1·d^-1), and high-dose STDP pretreatment group (40 mg·kg^-1·d^-1). The rats were intragastric administrated with STDP 2 weeks before operation. Moreover, the histopathological alterations were observed using optical microscopy and transmission electron microscopy. Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay. Mitochondrial functions including the mitochondrial permeability transition pore (mPTP) mtDNA copy number were determined and proteins of AKT/GSK3β were analyzed by Western blot.

Results: The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3β-Ser9 phosphorylation (P<0.05 or P<0.01).

Conclusion: STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.