摘要
目的:从p38有丝分裂原活化蛋白激酶(MAPK)通路研究复方参鹿颗粒(FSG)对较低危骨髓增生异常综合征(lower-risk MDS)骨髓CD34^+细胞凋亡的影响。方法:将60例lower-risk MDS患者随机分为FSG组和安特尔治疗组,每组30例。干预3个月。观察治疗前后两组患者血常规、骨髓CD34^+细胞凋亡率、骨髓单个核细胞(BMMNC)磷酸化p38(p-p38),p38,丝裂原活化蛋白激酶激酶(MKK)3/6,磷酸化p53(p-p53),B淋巴细胞瘤-2(Bcl-2),Bcl-2家族相关基因(Bcl-xl)蛋白以及p38 mRNA表达的变化。对照组7例为年龄匹配的非MDS引起的血细胞减少患者。结果:与治疗前比较,FSG组治疗后红细胞计数、血红蛋白量、血小板明显上升(P<0.05,P<0.01);安特尔组治疗后血红蛋白量有上升趋势,白细胞、红细胞、血小板计数差异无统计学意义。与对照组比较,治疗前FSG组lower-risk MDS骨髓CD34^+细胞凋亡率,p-p38,MKK3/6,p-p53蛋白表达增加,Bcl-xl蛋白表达降低(P<0.05,P<0.01),p38,Bcl-2蛋白和p38 mRNA表达无差异;FSG治疗后,CD34^+细胞凋亡率,p-p38,MKK3/6,p-p53蛋白表达均降低(P<0.05),但p-p38蛋白表达仍高于对照组(P<0.05),Bcl-xl蛋白表达增高(P<0.05)。安特尔组治疗前后CD34^+细胞凋亡率,p-p38,MKK3/6,p-p53,Bcl-xl蛋白表达差异均无统计学意义。对照组,lowerrisk MDS患者治疗前骨髓p-p38蛋白表达和CD34^+细胞凋亡率呈正相关(P<0.01)。FSG组治疗后骨髓CD34^+细胞凋亡率下降与p-p38蛋白表达水平下降呈正相关(P<0.01)。结论:FSG通过调控p38MAPK通路抑制骨髓CD34^+细胞凋亡,改善骨髓无效造血。
Objective:To explore the effects of compound Shenlu granule(FSG) on the apoptosis of CD34+cells of lower-risk myelodysplastic syndromes(MDS) bone marrow based on p38 mitogen-activated protein kinase(MAPK) pathway.Method:The 60 patients with lower-risk MDS patients were randomly divided into FSG group and andriol treatment group,30 cases in each group.All of the patients were treated for 3 months.Changes of blood routine,rates of apoptosis of CD34+cells,p-p38,p38,mitogen activated protein kinase kinase(MKK)3/6,p-p53,Bcl-xl,B-cell lymphoma-2(Bcl-2) protein and p38 mRNA expression levels in bone marrow mononuclear cells(BMMNC) were observed before and after treatment.7 cases from control group were agematched patients with non-MDS cytopenia.Result:After treatment,the red blood cells count,platelet count and hemoglobin count were increased in FSG group(P〈0.05,P〈0.01);hemoglobin count was increased in Andriol group after treatment and there was no significant difference in the count of WBC,RBC and PLT.As compared with control group,apoptosis rate of CD34+cells and expression levels of p-p38,MKK3/6,p-p53 protein were higher,and expression of Bcl-xl was lower in FSG group(P〈0.05,P〈0.01);while there was no significant difference in p38,Bcl-2 protein expression and p38 mRNA expression.After FSG treatment,CD34+cell apoptosis rate and levels of p-p38,MKK3/6,p-p53 protein expression in FSG group were lower(P〈0.05),p-p38 and Bcl-xl protein expression levels were higher than those in control group(P〈0.05).There was no significant difference in the apoptosis rate of CD34+,p-p38,MKK3/6,p-p53,Bcl-xl protein expression in Andriol group before and after treatment.P-p38 protein expression and CD34+cell apoptosis rate were positively correlated before treatment in control group(P〈0.01),and the decrease in apoptosis rate of CD34+was positively correlated with decrease in p-p38 protein expression after treatment in FSG group.Conclusion:FSG could inhibit the apoptosis of bone marrow CD34+cells by regulating the p38 MAPK pathway,and improve the ineffective hematopoiesis of bone marrow.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2017年第16期152-157,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81403233)