蓉黄颗粒治疗非透析期CKD-MBD肾虚湿热证患者的作用机制探讨

Mechanism of Rong Huang Granule in treatment of CKD-MBD patients with kidney deficiency damp heat syndrome in non-dialysis stage

目的观察非透析期慢性肾脏病矿物质和骨异常(CKD-MBD)肾虚湿热证患者骨代谢相关指标变化,探讨蓉黄颗粒治疗本病的作用机制。方法选择2017年12月至2019年12月安徽中医药大学第一附属医院肾内科收治的非透析期74例CKD-MBD肾虚湿热证患者,随机分为蓉黄颗粒组(RHKL组)和对照组(DZ组),每组37例;并选取20例健康体检者为正常组(ZC组)。DZ组予灌肠联合基础治疗;RHKL组在DZ组方案上配合蓉黄颗粒治疗,疗程均为12周。记录RHKL组和DZ组中医证候积分值,检测血肌酐(SCr)、血尿素氮(BUN)、血清钙、血清磷、甲状旁腺激素(iPTH)及血清Ⅰ型原胶原N端前肽(PINP)、Ⅰ型胶原羟基端肽β降解产物(β-CTX)水平。结果入选的74例患者中,4例出差断服蓉黄颗粒,3例自行加用百令胶囊,被剔除研究,最终纳入67例,RHKL组33例,DZ组34例。RHKL组治疗后CKD-MBD总有效率明显高于DZ组〔81.82%(27例)比61.76%(21例),P<0.05〕。两组治疗后中医证候积分值均较治疗前降低(均P<0.05),而RHKL组较DZ组降低更加明显(19.94±5.17比25.15±7.13,P<0.01)。两组治疗后血清钙、磷、iPTH、SCr、BUN及估算的肾小球滤过率(eGFR)水平均较治疗前明显改善(均P<0.05),且RHKL组各指标改善程度优于DZ组〔血清钙(mmol/L):2.17±0.09比2.10±0.11,血清磷(mmol/L):1.46±0.16比1.61±0.28,iPTH(ng/L):152.10±91.26比203.49±114.69,SCr(μmol/L):199.57±89.86比252.52±116.02,BUN(mmol/L):10.82±4.12比13.62±6.84,eGFR(mL/min):38.72±12.22比31.52±16.75,均P<0.05〕。治疗前RHKL组和DZ组血清PINP、β-CTX水平均显著高于ZC组(均P<0.01);治疗后RHKL组血清PINP、β-CTX水平较DZ组降低更为明显〔PINP(μg/L):84.41±35.94比106.43±51.28,β-CTX(ng/L):465.68±100.09比519.80±113.82,均P<0.05〕。结论蓉黄颗粒可以减轻患者临床表现,改善骨代谢相关指标的水平,这可能是蓉黄颗粒治疗非透析期CKD-MBD肾虚湿热证患者作用机制之一。

Objective To observe the changes of bone metabolism related indexes in patients with chronic kidney disease-mineral and bone disorder(CKD-MBD)with kidney deficiency damp heat syndrome in traditional Chinese medicine(TCM)in non-dialysis stage,and to explore the mechanism of Rong Huang Granule in the treatment of this disease.Methods Seventy-four patients with CKD-MBD kidney deficiency damp heat syndrome treated in the department of nephrology of the First Affiliated Hospital of Anhui University of Chinese Medicine from December 2017 to December 2019 were randomly divided into a ronghuang granule group(RHKL group)and a control group(DZ group),with 37 cases in each group;20 healthy subjects were selected as the normal group(ZC group).DZ group was given enema combined with basic treatment;RHKL group was treated with Rong Huang Granule on the basis of treatment in DZ group,and the course of treatment in the 3 groups was 12 weeks.The TCM syndrome integral values of RHKL group and DZ group were recorded,and the laboratory results of levels of serum creatinine(SCr),blood urea nitrogen(BUN),serum calcium,serum phosphorus,parathyroid hormone(iPTH),serum typeⅠprocollagen N-terminal propeptide(PINP),β-isomerized forms of typeⅠcollagen breakdown products(β-CTX)were measured.Results Among the 74 patients selected,7 patients were excluded from the study,because 4 cases stopped taking Rong Huang Granule on business trip and 3 cases added Bailing Capsule by themselves.Finally,67 cases were enrolled in the study,including 33 cases in RHKL group and 34 cases in DZ group.After treatment,the total effective rate of CKD-MBD patients in RHKL group was significantly higher than that in DZ group[81.82%(27 cases)vs.61.76%(21 cases),P<0.05].After treatment,the integral values of TCM syndrome in both groups were lower than those before treatment(both P<0.05),and the degree of lowering in RHKL group was more significant than that in DZ group(scores:19.94±5.17 vs.25.15±7.13,P<0.01).After treatment,the levels of serum calcium,phosphorus,iPTH,SCr,BUN and estimated glomerular filtration rate(eGFR)in the two groups were obviously improved compared with those before treatment(all P<0.05),and the improvement degrees of various indexes in RHKL group were better than those in the control group[serum calcium(mmol/L):2.17±0.09 vs.2.10±0.11,serum phosphorus(mmol/L):1.46±0.16 vs.1.61±0.28,iPTH(ng/L):152.10±91.26 vs.203.49±114.69,SCr(μmol/L):199.57±89.86 vs.252.52±116.02,BUN(mmol/L):10.82±4.12 vs.13.62±6.84,eGFR(mL/min):38.72±12.22 vs.31.52±16.75,all P<0.05].Before treatment,the serum PINP andβ-CTX levels of the RHKL and DZ groups were significantly higher than those of the ZC group(all P<0.01).After treatment,the serum PINP andβ-CTX levels in RHKL group were significantly lower than those in the control group[PINP(μg/L):84.41±35.94 vs.106.43±51.28,β-CTX(ng/L):465.68±100.09 vs.519.80±113.82,both P<0.05].Conclusion Rong Huang Granule can reduce the clinical manifestations of patients and improve the levels of bone metabolism related indicators,which may be one of the mechanisms of Rong Huang Granule in the treatment of CKD-MBD patients with kidney deficiency damp heat syndrome in non-dialysis stage.