帕立骨化醇对肾性骨病大鼠骨代谢及TGF-β/BMP-7/Smad通路的影响  

Effects of paricalcitol on bone metabolism and TGF-β/BMP-7/Smad signaling pathway in rats with renal osteodystrophy

作　　者：路琪 马学涛 李菲菲 LU Qi;MA Xuetao;LI Feifei(Department of Nephrology and Endocrinology,Zibo Integrated Traditional and Western Medicine Hospital,Zibo 255000,China)

机构地区：[1]淄博市中西医结合医院肾病内分泌科,淄博255000

出　　处：《中国免疫学杂志》2024年第7期1416-1421,共6页Chinese Journal of Immunology

摘　　要：目的:探讨帕立骨化醇对肾性骨病(ROD)大鼠骨代谢及转化生长因子-β(TGF-β)/骨形态发生蛋白-7(BMP-7)/Smad通路的影响。方法:将90只大鼠随机分为6组:对照组、模型组、帕立骨化醇低剂量(0.2μg/kg)组、帕立骨化醇中剂量(0.4μg/kg)组、帕立骨化醇高剂量(0.8μg/kg)组、骨化三醇(10μg/kg)组,每组15只,对照组大鼠以普通饲料喂养,其余各组大鼠用含有腺嘌呤的饲料喂养,诱导建立ROD模型。分组进行药物治疗后,测定各组大鼠肾功能指标血尿素氮(BUN)与血肌酐(Scr)水平、血钙与血磷水平、股骨骨密度(BMD)、股骨生物力学指标最大载荷、弹性模量与屈服载荷、血清炎症因子IL-6、IL-17水平;采用蛋白免疫印迹法检测骨组织TGF-β/BMP-7/Smad通路蛋白表达情况。再次取45只大鼠随机分为3组:帕立骨化醇(0.8μg/kg)组、TGF-β抑制(LY2157299,150 mg/kg)组、帕立骨化醇(0.8μg/kg)+TGF-β抑制(LY2157299,150 mg/kg)组,每组15只,同样方法建立ROD模型。分组以药物治疗后,测定各组大鼠肾功能指标与股骨生物力学指标水平。结果:与对照组比较,模型组大鼠血钙水平、BMD、弹性模量、最大载荷、屈服载荷、骨组织TGF-β/BMP-7/Smad通路蛋白TGF-β及BMP-7表达、p-Smad3/Smad3显著降低(P<0.05),BUN与Scr水平、血磷水平、血清IL-6与IL-17水平显著升高(P<0.05)。与模型组比较,帕立骨化醇低、中、高剂量组和骨化三醇组大鼠血钙水平、BMD、弹性模量、最大载荷、屈服载荷、骨组织TGF-β/BMP-7/Smad通路蛋白TGF-β及BMP-7表达、p-Smad3/Smad3均升高,BUN与Scr水平、血磷水平、血清IL-6与IL-17水平均降低,且帕立骨化醇各组之间呈剂量依赖性(P<0.05),帕立骨化醇高剂量组和骨化三醇组比较,大鼠各指标差异无统计学意义(P>0.05)。与帕立骨化醇+TGF-β抑制组比较,帕立骨化醇组大鼠肾功能指标BUN、Scr与血磷水平降低(P<0.05),血钙水平、BMD、弹性模量、最大载荷、�Objective:To investigate the effects of paricalcitol on bone metabolism and transforming growth factor-β(TGF-β)/bone morphogenetic protein-7(BMP-7)/Smad signaling pathway in rats with renal osteodystrophy(ROD).Methods:Total 90 rat were randomly divided into 6 groups:control group,model group,paricalcitol low-dose(0.2μg/kg)group,paricalcitol medium-dose group(0.4μg/kg)group,paricalcitol high-dose(0.8μg/kg)group,calcitriol(10μg/kg)group,with 15 rats in each group.Rats in control group were fed with ordinary feed,and rats in other groups were fed with feed containing adenine to induce the establishment of ROD model.After grouping and drug treatment,the blood urea nitrogen(BUN)and blood creatinine(Scr)levels,blood calcium and blood phosphorus levels,femoral bone mineral density(BMD),maximum load,elasticity modulus and yield load,serum inflammatory factors IL-6 and IL-17 levels of each group were measured;and the expression of TGF-β/BMP-7/Smad pathway protein in bone tissue was detected with Western blot.Another 45 rats were randomly divided into 3 groups:paricalcitol(0.8μg/kg)group,TGF-βinhibition(LY2157299,150 mg/kg)group,paricalcitol(0.8μg/kg)+TGF-βinhibition(LY2157299,150 mg/kg)group,with 15 rats in each group.ROD model was established with the same method.After drug treatment,the renal function indexes and femoral biomechanical indexes were measured.Results:Compared with control group,the blood calcium level,BMD,elastic modulus,maximum load,yield load,bone tissue TGF-β/BMP-7/Smad pathway proteins TGF-βand BMP-7 expressions,p-Smad3/Smad3 were significantly reduced in the model group(P<0.05),the BUN and Scr levels,blood phosphorus level,and serum IL-6 and IL-17 levels were significantly increased(P<0.05).Compared with the model group,the blood calcium level,BMD,elastic modulus,maximum load,yield load,bone tissue TGF-β/BMP-7/Smad pathway protein TGF-βand BMP-7 expression,p-Smad3/Smad3 were significantly increased in the paricalcitol low,medium and high dose groups and calcitriol group(P<0.05),the BUN

关 键 词：帕立骨化醇 肾性骨病 骨代谢 转化生长因子-β/骨形态发生蛋白-7/Smad信号 

分 类 号：R692[医药卫生—泌尿科学]