肾衰Ⅱ号方颗粒联合西医一体化方案治疗原发性慢性肾脏病3~4期患者临床疗效及对血清自噬相关蛋白的影响

Clinical Efficacy of Shen Shuai II Granules Combined with Integrated Western Medicine Therapy in Patients with Primary Chronic Kidney Disease in Stages 3-4 and Its Effects on Expression of Serum Autophagy Related Proteins

目的观察肾衰Ⅱ号方颗粒联合西医一体化方案治疗原发性慢性肾脏病(CKD)3~4期脾肾气虚证、湿浊瘀阻证患者临床疗效及对血清自噬相关蛋白的影响。方法采用随机数字表法将88例患者分为治疗组、对照组各44例。2组均予西医一体化方案治疗,治疗组在此基础上予肾衰Ⅱ号方颗粒,对照组予肾衰Ⅱ号方免煎安慰剂,每次1袋,每日2次,口服。2组均连续治疗24周。观察2组临床疗效,比较2组治疗前后中医症状评分、血肌酐(Scr)、血尿素氮(BUN)、尿酸(UA)、血钙(Ca^(2+))、血磷(P^(3-))、甲状旁腺激素(PTH)、24 h尿蛋白定量(24 UPro)水平;ELISA法检测2组治疗前后血清自噬相关蛋白Beclin-1、Atg7、LC3-Ⅱ水平;监测2组安全性指标。结果治疗过程中治疗组、对照组各脱落4例。治疗组总有效率为55%(22/40),对照组为30%(12/40),治疗组疗效优于对照组(P<0.01)。与本组治疗前比较,治疗组治疗后各项中医症状评分降低(P<0.01),Scr、BUN、UA、P3-、PTH和24 UPro水平下降(P<0.05,P<0.01),肾小球滤过率(e GFR)上升(P<0.01),对照组治疗后Scr上升(P<0.05),eGFR下降(P<0.01);2组治疗后比较,治疗组各项中医症状评分、Scr、BUN、UA、P^(3-)、PTH和24 UPro水平低于对照组(P<0.01,P<0.05),eGFR高于对照组(P<0.01)。与本组治疗前比较,治疗组治疗后血清Beclin-1、Atg7、LC3-Ⅱ水平上升(P<0.01,P<0.05),对照组治疗后血清Beclin-1水平下降(P<0.01);2组治疗后比较,治疗组上述指标改善均优于对照组(P<0.01,P<0.05)。相关性分析显示,Beclin-1、Atg7、LC3-Ⅱ与Scr、BUN呈负相关(P<0.05),与eGFR呈正相关(P<0.05)。2组治疗过程中均未见明显不良反应。结论肾衰Ⅱ号方颗粒联合西医一体化方案治疗原发性CKD 3~4期脾肾气虚证、湿浊瘀阻证患者疗效显著,可有效减轻临床症状,改善肾功能,延缓CKD进展,其作用机制可能与改善肾脏自噬水平有关。

Objective To observe the clinical efficacy of Shen Shuai II Granules combined with integrated Western medicine therapy in patients with primary chronic kidney disease(CKD)in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis,and its effects on expression of serum autophagy related proteins.Methods Totally 88 patients were randomly divided into treatment group and control group,with 44 cases in each group.Both groups were given an integrated Western medicine therapy.On this basis,the treatment group was given Shen Shuai II Granules,while the control group was given Shen Shuai II placebo,1 bag at a time,twice a day,orally.The treatment for both groups lasted for 24 weeks.The clinical efficacy of the two groups was observed.The TCM symptom scores,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),blood calcium(Ca^(2+)),blood phosphorus(P^(3-)),parathyroid hormone(PTH),and 24-hour urinary protein quantification(24 UPro)before and after treatment were compared in the two groups.The serum levels of autophagy related protein Beclin-1,Atg7,and LC3-Ⅱwere detected by ELISA before and after treatment in the two groups.Safety indexes of both groups were monitored.Results During the treatment,4 cases fell off in the treatment group and 4 cases in the control group.The total effective rate in the treatment group was 55%(22/40),while that in the control group was 30%(12/40).The therapeutic effect in the treatment group was better than that in the control group(P<0.01).Compared with before treatment,the TCM symptom scores in the treatment group decreased after treatment(P<0.01),the levels of Scr,BUN,UA,P^(3-),PTH,and 24 UPro decreased(P<0.05,P<0.01),while eGFR increased(P<0.01).The levels of Scr in the control group increased(P<0.05),while eGFR decreased(P<0.01).After treatment,the treatment group had lower various TCM symptom scores,Scr,BUN,UA,P^(3-),PTH,and 24 UPro levels than the control group(P<0.01,P<0.05),and higher eGFR than the control group(P<0.01).Compared with before treatment,the serum levels of Beclin-1,Atg7,and LC3-Ⅱincreased in the treatment group after treatment(P<0.01,P<0.05),while the serum level of Beclin-1 decreased in the control group after treatment(P<0.01).After treatment,the improvement of the above indicators in the treatment group were better than those in the control group(P<0.01,P<0.05).Correlation analysis showed that Beclin-1,Atg7,and LC3-Ⅱwere negatively correlated with Scr and BUN(P<0.05),and positively correlated with eGFR(P<0.05).There was no obvious adverse reaction in both groups.Conclusion The combination of Shen Shuai II Granules and integrated Western medicine therapy for the treatment of primary CKD in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis has confirmed efficacy,which can effectively alleviate clinical symptoms,improve renal function,and delay the progression of CKD.The mechanism may be related to improving the level of autophagy in renal.