银杏内酯B通过激活ITP小鼠mTOR信号通路调节lncRNA PVT1促进Treg/Th17免疫平衡而抑制炎症反应的机制研究OA

Objective To investigate the role of Ginkgolide B in activating mammalian target of rapamycin in immune thrombo-cytopenic purpura(ITP).lncro RNA plasmacytoma variant translocation 1(lncro RNA plasmacytoma variant translocation 1,mTOR)signaling pathway regulates long non-coding RNA human plasmacytoma variant translocation 1,lncRNA PVT1)pro-motes the immune balance of regulatory T cell/T helper cell-17(Treg/Th17)and inhibits the inflammatory response.Methods 80 male SD mice were randomly divided into normal group,model group,low-dose group,high-dose group,with 20 mice in each group,and were administered continuously for 14 days.The qRT-PCR was used to detect serum lncRNA PVT1 expression,Treg/Th17 cells were detected by flow cytometry,the expressions of phosphatei-dylinositol 3 kinase(PI3K),Akt and mTOR were de-tected by Western Blot.Serum Interleukin-4(IL-4),interferon-γ(IFN-γ)and platelet count(PLT)were detected.Results Compared with the control group,the model group exhibited significantly elevated levels of serum lncRNA PVT1,Th17 cells,and IFN-γ,while Treg cells,Treg/Th17 ratio,PI3K,Akt,mTOR protein levels,IL-4,and platelet count(PLT)were significantly decreased(t=2.510～54.899,all P<0.05).Compared with the model group,both the low-dose and high-dose groups showed reduced levels of lncRNA PVT1(1.99±0.14,1.25±0.11 vs 2.39±0.15),Th17 cells(1.76%±0.32%,0.87%±0.04%vs 5.28%±1.21%),and IFN-γ(7.65±0.28 pg/ml,6.84±0.33 pg/ml vs 8.45±0.36 pg/ml)(tlow-dose=8.718,8.782,3.292;thigh-dose=27.408,9.789,6.542),while Treg cells(3.46%±0.43%,4.77%±0.51%vs 2.41%±0.44%),Treg/Th17 ratio(1.98±0.16,4.24±1.02 vs 0.45±0.05),PI3K(0.88±0.08,1.22±0.21 vs 0.45±0.05),Akt(0.66±0.07,1.11±0.11 vs 0.21±0.02),mTOR protein(0.70±0.08,1.21±0.13 vs 0.45±0.06),IL-4(12.28±1.28 pg/ml,13.08±1.01 pg/ml vs 11.45±1.05 pg/ml)and PLT[(526.99±50.34)×109/L,(880.37±52.78)×109/L vs(218.58±50.35)×109/L]were increased(tlow-dose=4.943～27.643;thigh-dose=7.766～40.818),with all differences being statistically significant(all P<0.05).Compared with the low-dose group,the high-dose group demonstrated further reductions in lncRNA PVT1,Th17 cells and IFN-γ,while Treg cells,Treg/Th17 ratio,PI3K,Akt,mTOR protein levels,IL-4 and PLT were further increased(t=2.411～21.667,all P<0.05).Conclusions Ginkgolide B can activate mTOR signaling pathway,regulate lncRNA PVT1,promote Treg/Th17 immune balance,and inhibit inflammation in ITP mice,increases platelet count.