Salidroside regulates imbalance of Th17/Treg and promotes ischemic tolerance by targeting STAT-3 in cerebral ischemia-reperfusion injury

INTRODUCTION: The balance between Th17 and Treg cells controls the immune response and is an important regulator of helper T cells acting on autoimmune diseases. Focal cerebral ischemia-reperfusion injury can induce imbalance of Th17/Treg cells in the brain and the peripheral immune system of rats. The aim of this study was to investigate the effect of salidroside (Sal) on the ratio of Th17 and Treg cells in an adult rat model of middle cerebral artery occlusion (MCAO). MATERIAL AND METHODS: Forty rats were divided into 4 groups: normal group, sham group, surgery group, and Sal group. After treatment, the neurological deficits in rats were evaluated. Peripheral blood mononuclear cells were isolated and the count of Th17 and Treg cells was detected by flow cytometry. The infarct size and expression of RORγt and Foxp3 were detected in rat brain tissue. Rat spleen cells were isolated, CD4(+) T cells were purified by immunomagnetic beads. Treg cells were induced by adding cytokine TGF-β. Th17 cells were induced by adding cytokine IL-6. The expression of STAT-3 was inhibited by SiRNA, and the effect of Sal on the differentiation of Th17/Treg cells was analyzed. The expression levels of IL-6, TNF-α, MCP-1, STAT-3 and NF-κ-B2 proteins were examined. RESULTS: The results show that MCAO can induce an imbalance of Th17 and Treg cells in peripheral blood of rats. Sal treatment can significantly reduce the neurological deficit and infarct size of MCAO rats, reverse the oxidative stress of rat brain tissue, and inhibit the apoptosis of brain cells in MCAO rats. In the brain tissue of MCAO rats, Sal could significantly inhibit the expression of IL-6, TNF-α, MCP-1, STAT-3 and NF-κ-B2. Down-regulation of STAT-3 significantly reversed the therapeutic effects of Sal treatment. CONCLUSIONS: Our results indicate that Sal can increase the tolerance of rat brain tissue to ischemia, inhibit cell apoptosis and reduce oxidative stress by targeting STAT-3.