硫代硫酸钠治疗尿毒症钙化的效果及对血清钙化因子、miR-21和miR-125b的影响

Effect of sodium thiosulfate on uremic calcification and its influence on serum calcification factors,miR-21 and miR-125b

目的探究硫代硫酸钠(STS)治疗尿毒症钙化的效果及对血清钙化因子、微小RNA(miR)-21和miR-125b的影响。方法前瞻性选取2020年12月至2022年12月于海口市第三人民医院就诊的102例终末期肾病(ESRD)合并冠状动脉钙化(CAC)患者作为研究对象,按照随机数字表法将其分为研究组(n=51)和对照组(n=51)。对照组进行常规治疗,研究组在对照组的基础上联合STS静脉注射。比较两组患者治疗前后血管钙化指标[冠状动脉钙化(CAC)评分、心踝血管指数(CAVI)],钙磷代谢指标[血钙、血磷、钙磷乘积、甲状旁腺激素(PTH)],骨钙代谢指标[成纤维细胞生长因子23(FGF23)、骨形成蛋白(BMP-2)和骨碱性磷酸酶(bALP)],炎症因子指标[C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]以及外周血miR-21、miR-125b表达水平变化,统计治疗期间不良反应发生情况。结果治疗3个月后,两组CAC评分、CAVI均下降,且研究组CAC评分、CAVI分别为(101.34±10.64)分、8.64±1.24,均低于对照组[(124.24±12.48)分、10.01±1.22],差异均有统计学意义(P<0.05)。治疗3个月后,两组血清钙、血清磷、钙磷乘积和iPTH水平均较治疗前下降,且研究组血清钙、血清磷、钙磷乘积和iPTH水平分别为(2.01±0.34)mmoL/L、(1.94±0.22)mmoL/L、(3.91±0.35)mmoL/L、(3.42±0.34)ng/mL,均低于对照组[(2.16±0.38)mmoL/L、(2.23±0.27)mmoL/L、(4.92±0.43)mmoL/L、(4.74±0.41)ng/mL],差异均有统计学意义(P<0.05)。治疗3个月后,两组FGF23、BMP-2、bALP、hs-CRP、IL-6和TNF-α水平均较治疗前下降,且研究组FGF23、BMP-2、bALP、hs-CRP、IL-6和TNF-α水平分别为(208.41±34.84)pg/mL、(81.35±9.23)ng/L、(9.34±2.87)IU/L、(6.31±2.21)mg/L、(92.36±10.27)ng/L、(29.81±4.14)pg/mL,均低于对照组[(242.32±38.34)pg/mL、(90.48±10.31)ng/L、(14.54±3.47)IU/L、(10.29±3.34)mg/L、(101.44±12.14)ng/L、(37.59±4.76)pg/mL],差异均有统计学意义(P<0.05)。治疗3个月后,两组miR-21水平较治疗前下降,miR-125b水平较治疗前上升,且研究组miR-21水平为1.64±0.32,低于对照组(2.44±0.78),miR-125b水平为1.94±0.51,高于对照组(1.67±0.44),差异均有统计学意义(P<0.05)。两组不良反应发生情况比较差异无统计学意义(P<0.05)。结论在钙化性尿毒症动脉病治疗时,补充硫代硫酸钠注射液可改善患者血管钙化情况,调节钙磷平衡及iPTH水平,调控血管钙化因子,促使炎症因子水平恢复,调控miR-21、miR-125b基因表达,具有良好的治疗效果和安全性。

Objective To explore the effect of sodium thiosulfate(STS)in the treatment of uremic calcification and its influence on serum calcification factors,microRNA(miR)-21 and miR-125b.Methods A total of 102 patients with end-stage renal disease(ESRD)complicated with coronary artery calcification(CAC)treated in Haikou Third People's Hospital from December 2020 to December 2022 were prospectively selected as study subjects,and divided into study group(n=51)and control group(n=51)according to the random number table method.The control group received conventional treatment,and the study group was given STS intravenous injection on the basis of the control group.Vascular calcification indicators[coronary artery calcification(CAC)score,cardio-ankle vascular index(CAVI)],calcium-phosphorus metabolism indicators[serum calcium,serum phosphorus,calcium-phosphorus product,parathyroid hormone(PTH)],bone calcium metabolism indicators[fibroblast growth factor 23(FGF23),bone morphogenetic protein(BMP-2),bone alkaline phosphatase(bALP)],inflammatory factors[C-reactive protein(hs-CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]and expression levels of peripheral blood miR-21 and miR-125b were compared between the two groups before and after treatment,and the adverse reactions during treatment were counted.Results After 3 months of treatment,the CAC score and CAVI of two groups were lower than those before treatment,and the CAC score and CAVI of the study group were(101.34±10.64)points and 8.64±1.24,respectively,which were lower than those of the control group[(124.24±12.48)points and 10.01±1.22],the differences were statistically significant(P<0.05).After 3 months of treatment,the levels of serum calcium,serum phosphorus,calcium phosphorus product,and iPTH in two groups were lower than those before treatment,and the levels of serum calcium,serum phosphorus,calcium phosphorus product,and iPTH in the study group were(2.01±0.34)mmoL/L,(1.94±0.22)mmoL/L,(3.91±0.35)mmoL/L,and(3.42±0.34)ng/mL,respectively,which were lower than those in the control group[(2.16±0.38)mmoL/L,(2.23±0.27)mmoL/L,(4.92±0.43)mmoL/L,and(4.74±0.41)ng/mL],the differences were statistically significant(P<0.05).After 3 months of treatment,the levels of FGF23,BMP-2,bALP,hs-CRP,IL-6,and TNF-αin two groups were lower than those before treatment,and the levels of FGF23,BMP-2,bALP,hs-CRP,IL-6,and TNF-αin the study group were(208.41±34.84)pg/mL,(81.35±9.23)ng/L,(9.34±2.87)IU/L,(6.31±2.21)mg/L,(92.36±10.27)ng/L,and(29.81±4.14)pg/mL,respectively,which were lower than those in the control group[(242.32±38.34)pg/mL,(90.48±10.31)ng/L,(14.54±3.47)IU/L,(10.29±3.34)mg/L,(101.44±12.14)ng/L,(37.59±4.76)pg/mL],and the differences were statistically significant(P<0.05).After 3 months of treatment,the levels of miR-21 in two groups were lower than those before treatment,while the levels of miR-125b were higher than those before treatment,the level of miR-21 in the study group was 1.64±0.32,which was lower than that in the control group(2.44±0.78),and the level of miR-125b was 1.94±0.51,which was higher than that in the control group(1.67±0.44),and the differences were statistically significant(P<0.05).There were no statistically significant differences in the adverse reactions between the two groups(P<0.05).Conclusion In the treatment of arterial disease of calcified uremia,the supplementation of sodium thiosulfate injection can improve the vascular calcification,regulate the calcium-phosphorus balance and iPTH level,control the vascular calcification factors,and promote the recovery of inflammatory factors,regulate the expression of miR-21 and miR-125b genes,and it has good therapeutic effect and safety.