清肾颗粒对非透析慢性肾脏病湿热证患者血清microRNA-21、Wnt4及β-catenin的影响

Effect of Qingshen Granule on Blood MicroRNA-21,Wnt4,andβ-catenin in Patients with Non-dialysis Chronic Kidney Disease with Damp-Heat Syndrome

目的观察清肾颗粒对非透析慢性肾脏病(chronic kidney disease,CKD)湿热证患者血microRNA-21、Wnt4及β-catenin的影响,探讨其保护肾功能、改善临床症状的作用机制。方法选取66例符合纳入标准的CKD湿热证患者,最终完成64例,对照组和观察组各32例。对照组采用CKD常规基础治疗,观察组在对照组治疗基础上加用清肾颗粒口服,疗程均为12周。观察和比较两组患者治疗前后中医症状积分及证候疗效,肾功能指标[血尿素氮(blood urea nitrogen,BUN)、肾小球滤过率(estimated glomerular filtration rate,eGFR)、血清肌酐(serum creatinine,SCr)],微炎症、营养指标[超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、白蛋白(albumin,Alb)、前白蛋白(prealbumin,PAB)],血清microRNA-21、Wnt4及β-catenin水平。结果两组患者治疗后中医症状积分较治疗前均显著降低(P<0.05),且观察组降低程度显著大于对照组(P<0.05);两组患者临床疗效比较,差异无统计学意义(P>0.05)。观察组BUN、SCr水平,eGFR较治疗前显著改善(P<0.05),且改善程度显著优于对照组(P<0.05);与治疗前比较,两组患者治疗后血清hs-CRP水平均显著降低(P<0.05),Alb、PAB水平均显著升高(P<0.05),且观察组血清hs-CRP、Alb、PAB水平改善程度优于对照组(P<0.05);治疗前两组患者血清microRNA-21、Wnt4、β-catenin水平均显著高于正常组(P<0.05),观察组患者治疗后血清microRNA-21、Wnt4、β-catenin水平均显著降低(P<0.05),且降低程度显著大于对照组(P<0.05)。结论清肾颗粒能够改善CKD湿热证患者肾功能及微炎症、营养不良状态,减轻临床症状,其机制可能与降低microRNA-21表达水平,靶向抑制Wnt/β-catenin信号通路有关。

Objective To investigate the effect of Qingshen Granule on blood microRNA-21,Wnt4,andβ-catenin in patients with non-dialysis chronic kidney disease(CKD)with damp-heat syndrome,as well as its mechanism of action in protecting renal function and improving clinical symptoms.Methods A total of 66 CKD patients with damp-heat syndrome who met the inclusion criteria were enrolled,and finally 64 patients completed the study,with 32 patients in the control group and 32 in the observation group.The patients in the control group received routine basic treatment for CKD,while those in the observation group received oral administration of Qingshen Granule in addition to the treatment in the control group;the course of treatment was 12 weeks for both groups.The two groups were observed and compared in terms of traditional Chinese medicine(TCM)symptom score,treatment outcome of TCM syndrome,renal function parameters[blood urea nitrogen(BUN),estimated glomerular filtration rate(eGFR),and serum creatinine(SCr)],microinflammation and nutritional indices[hypersensitive C-reactive protein(hs-CRP),albumin(Alb),and prealbumin(PAB)],and the levels of microRNA-21,Wnt4,andβ-catenin in blood.Results After treatment,both groups had a significant reduction in TCM symptom score(P<0.05),and the observation group had a significantly greater reduction than the control group(P<0.05).There was no significant difference in the distribution of clinical outcomes between the two groups(P>0.05).After treatment,the observation group had significant improvements in the levels of BUN,SCr,and eGFR,with significantly greater improvements than the control group(P<0.05);after treatment,both groups had a significant reduction in the serum level of hs-CRP(P<0.05)and significant increases in the levels of Alb and PAB(P<0.05),and the observation group had significantly greater improvements in hs-CRP,Alb,and PAB than the control group(P<0.05).Before treatment,the two groups had significantly higher levels of microRNA-21,Wnt4,andβ-catenin than the normal group(P<0.05),and after treatment,the observation group had significant reductions in the levels of microRNA-21,Wnt4,andβ-catenin(P<0.05),with significantly greater reductions than the control group(P<0.05).Conclusion Qingshen Granule can improve renal function,microinflammation,and malnutrition and alleviate clinical symptoms in CKD patients with damp-heat syndrome,possibly by downregulating the expression level of microRNA-21 and inhibiting the Wnt/β-catenin signaling pathway.