补肾活血方通过调控OPG/RANK/RANKL系统改善慢性肾功能衰竭ROD大鼠骨代谢异常的作用机制研究  

Study on the mechanism of Bushen Huoxue Recipe in improving abnormal bone metabolism in ROD rats with chronic renal failure by regulating OPG/RANK/RANKL system

作　　者：孟祥飞[1] 柳诗意[1] 刘世巍[1] 张宁[1] MENG Xiangfei;LIU Shiyi;LIU Shiwei;ZHANG Ning(Department of Nephrology and Endocrinology,Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China)

机构地区：[1]中国中医科学院望京医院肾病内分泌科,北京100102

出　　处：《中华中医药杂志》2023年第8期3821-3826,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81973801);国家自然科学基金青年科学基金项目(No.81904156)。

摘　　要：目的:观察补肾活血方对慢性肾功能衰竭大鼠肾性骨营养不良(ROD)骨保护素(OPG)/核因子κB活化因子受体(RANK)/核因子κB活化因子受体配体(RANKL)系统的作用,探讨其可能机制。方法:90只SD大鼠随机分为正常组(10只)、模型组(40只)、中药组(40只)。实验第1-6周,中药组和模型组大鼠按照250mg·kg^(-1)·d^(-1)的剂量给予腺嘌呤混悬液灌胃及含1.2%高磷饲料喂养,第7—8周改为腺嘌呤混悬液隔日灌胃。同时中药组按照55g·kg^(-1)·d^(-1)剂量给予补肾活血方中药汤剂灌胃;模型组、正常组以等剂量0.9%氯化钠溶液灌胃,共给药8周。取肾组织进行HE染色观察病理变化,腹主动脉取血检测血肌酐(Scr)、尿素氮(BUN)、全段甲状旁腺激素(iPTH)、血磷(P)、血钙(Ca)水平,ELISA法检测各组大鼠血清抗酒石酸酸性磷酸酶(TRAP)浓度,Real-timePCR法检测脊髓细胞PTH、OPG、RANK、RANKLmRNA表达。结果:与正常组比较,模型组肾脏切面皮质与髓质分界不清晰,肾小球数目明显减少,残存肾小球囊腔明显扩张,包曼氏囊壁增厚,大量肾小管破坏、萎缩、消失;中药组较模型组明显改善。与正常组比较,模型组大鼠血BUN、Scr、P、iPTH升高,血Ca降低,PTH、RANKLmRNA表达均上调,OPGmRNA表达下调,OPG/RANKL降低,差异均有统计学意义(P<0.01);与模型组比较,中药组大鼠血BUN、Scr、iPTH、P降低,血Ca升高,PTH、RANKLmRNA表达均下调,OPGmRNA表达上调,OPG/RANKL升高,差异均有统计学意义(P<0.05,P<0.01)。各组大鼠血清TRAP浓度比较,差异无统计学意义。结论:补肾活血方能够调节钙磷代谢及骨代谢,上调OPGmRNA表达,下调PTH、RANKLmRNA表达,进而改善慢性肾功能衰竭ROD大鼠的肾脏功能及肾脏病理,这可能是其治疗慢性肾功能衰竭的作用机制之一。Objective:To observe the effect of Bushen Huoxue Recipe(BHR)on alleviate renal osteodystrophy(ROD)in chronic renal failure rats by regulating OPG/RANK/RANKL system and to explore its possible mechanism.Methods:Ninety SD rats were divided into the model group(40 rats),the BHR group(40 rats)and the normal group(10 rats)randomly.Rats in the model group and the BHR group were administered with 250 mg·kg^(-1)·d^(-1) adenine suspension by gastroagavage and fed with 1.2%high phosphorus forage,in the first 6 weeks,and then gastric administration of adenine suspension was changed to once per two days in the following 7-8 weeks.Rats in the BHR group were administered with BHR at the daily dose of 55 g·kg^(-1)·d^(-1)by gastrogavage in the first 8 weeks,once per day.Equal volume of normal saline was given to rats in the normal group and the model group by gastrogavage for 8 weeks.Histological changes in renal tissue were observed by HE staining and alizarin red staining respectively.Levels of serum creatinine(Scr),blood urea nitrogen(BUN),intact parathyroid hormone(iPTH),phosphorus(P),calcium(Ca)in serum were detected.The level of tartrate resistant acid phosphatase(TRAP)were detected by ELISA.The expression levels of PTH,OPG,RANK,RANKL mRNA were detected by Real-time PCR.Results:Compared with the normal group,the boundary between the incisal cortex and medulla of the kidney was not clear in the model group,the number of glomerulus was significantly reduced,the remaining glomerulus capsule was significantly enlarged,the wall of Bauman's capsule was thickened,and a large number of renal tubules were broken,atrophy and disappeared.The BHR group was better than the model group.Compared with normal group,serum levels of P,Scr,BUN and iPTH significantly increased,serum Ca level significantly decreased,mRNA expressions of PTH,RANKL mRNA also increased and mRNA expressions of OPG and OPG/RANKL decreased in the model group(P<0.01).Compared with the model group,serum levels of P,Scr,BUN,and iPTH levels significantly decreased,ser

关 键 词：慢性肾功能衰竭 肾性骨营养不良 补肾活血方 骨保护素 核因子κB活化因子受体 核因子κB活化因子受体配体 

分 类 号：R285.5[医药卫生—中药学]