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Objective:To explore the curative effect of methylprednisolone combined with methotrexate in the treatment of ankylosing spondylitis (AS) and its regulation of serum interleukin (IL)-17/IL-4.Methods:A total of 117 patients with AS in the First Hospital of Baoding from July 2016 to June 2019 were selected as prospective research subjects, and they were simply randomized into three groups, with 39 cases in each group. The control group A was treated with methotrexate, the control group B was treated with methylprednisolone, and the observation group was treated with methotrexate combined with methylprednisolone. The chi-square test was used to compare the clinical efficacy and the incidence of adverse reactions in the three groups. F-test was used to compare the thoracolumbar spine mobility, Bath AS disease activity index (BASDAI), Bath AS function index (BASFI) scores, the levels of serum high mobility protein 1 (HMGB1), matrix metalloproteinase-3 (MMP-3), interleukin (IL)-4, IL-17, and IL-17/IL-4 before and after the treatment of the three groups. Results:The total effective rate of treatment in the observation group was better than that in the control groups A and B :92.31%(36/39) vs. 74.36%(29/39) and 69.23%(27/39), P<0.05. After the course of treatment, the BASDAI and BASFI scores in the observation group were lower than those in the control group A and B, and the thoracolumbar spine mobility were higher than those in the control group A and B: (3.36 ± 1.03) scores vs. (4.62 ± 1.19), (4.98 ± 1.25) scores; (3.70 ± 0.89) scores vs. (4.36 ± 0.96), (4.64 ± 0.95) scores; (4.96 ± 1.17) cm vs. (4.18 ± 1.02), (3.98 ± 1.15) cm, (5.93 ± 1.32) cm vs.(5.02 ± 1.15), (4.92 ± 1.25)cm, P<0.05. After the course of treatment, serum HMGB1, MMP-3, IL-17, IL-17/IL-4 in the observation group were lower than those in the control group A and B: (20.25 ± 6.41) μg/L vs. (27.81 ± 7.63), (29.26 ± 7.31) μg/L; (4.83 ± 1.06) μg/L vs. (9.26 ± 1.25), (9.71 ± 1.28) μg/L; (13.41 ± 5.06)ng/L vs.(17.62 ± 5.61), (19.06 ± 6.14) ng/L; 0.51 ± 0.27 vs. 0.92 ± 0.41, 1.04 ± 0.45, P<0.05; and IL-4 was higher than that in the control groups A and B: (26.15 ± 4.94) ng/L vs. (19.16 ± 5.14), (18.32 ± 5.26) ng/L, P<0.05. There was no significant difference in the incidence of adverse reactions among the three groups ( P>0.05). Conclusions:The combination of methylprednisolone and methotrexate in the treatment of AS can significantly reduce serum HMGB1 and MMP-3 levels, regulate serum IL-17/IL-4 and further improve the therapeutic effect, and it has high safety.
RESUMO
Objective To investigate the effects of HMGB1 small interference RNA (siRNA) on retinal vascular endothelial cells.Methods siRNA was used to inhibit the expression of HMGB1,followed by the application of CCK8 assay,Hochest33342 staining and flow cytometry to observe the effects of HMGB1 siRNA on retinal vascular endothelial cells in high glucose environment.Meanwhile,the expression of proteins related to apoptosis was detected by Western blot.Results The transfection of HMGB1 siRNA down-regulated the protein expression level of HMGB1 by 73％ in siRNA group compared with normal control (NC) group (P ＜ 0.05),and the protein expression level of HMGB1 in siRNA group was decreased by 75％ compared with scr-siRNA group (P ＜ 0.05).There was no significant difference between NC group and scrsiRNA group (P ＞ 0.05).The total apoptotic rate of NC group,high-glucose group,scrsiRNA group and siRNA group was (0.40 ± 0.03)％,(49.80 ± 3.50)％,(47.60 ±1.98) ％ and (23.60 ± 2.40) ％ by flow cytometry.Compared with NC group,the apoptotic rates of high-glucose group,scr-siRNA group and siRNA group were increased (all P ＜ 0.05).Compared with scr-siRNA group,the apoptotic rate of HRECs in siRNA group was reduced,with significant statistical difference (P ＜ 0.05).There was no significant difference in the rate of cell apoptosis between scr-siRNA group and high-glucose group (P ＞ 0.05).Compared with the NC group,the protein expression level of cleavedcaspase3 protein in high-glucose group and scr-siRNA group were increased by (233 ±10) ％ and (266 ± 22) ％,respectively (both P ＜ 0.05);compared with scr-siRNA group,the protein expression level of cleaved-caspase 3 in siRNA group was reduced by (43 ±3) ％ (P ＜ 0.05);and there was no significant difference in the protein expression of cleaved-caspase 3 in high-glucose group and scr-siRNA group (P ＞ 0.05).Compared with the NC group,the protein expression of B-cell lymphoma-2 (Bcl-2) in high-glucose group and scr-siRNA group was decreased by (32 ± 2) ％ and (29 ± 3) ％,accordingly (both P ＜ 0.05);compared with scr-siRNA group,the protein expression level of Bcl-2 in siRNA group was increased by (42 ± 2) ％ (P ＜ 0.05);and there was no significant difference in the protein expression of Bcl-2 in high-glucose group and scr-siRNA group (P ＞ 0.05).Conclusion HMGB1 siRNA can reduce the apoptosis of retinal vascular endothelial cells in high glucose environment by inhibiting the activation of cleavedcaspase3 and increasing the expression of Bcl-2.