活血益肾方联合钠-葡萄糖协同转运蛋白2抑制剂治疗糖尿病肾脏疾病的临床研究

Treatment of diabetic kidney disease by Huoxue Yishen Recipe plus sodium-glucose co-transporter 2 inhibitors

目的分析活血益肾方联合钠-葡萄糖协同转运蛋白2(sodium-glucose co-transporter 2,SGLT2)抑制剂治疗糖尿病肾脏疾病(diabetic kidney disease,DKD)的效果。方法选取2020年1月至2021年1月廊坊市中医医院内分泌科收治的DKD患者200例,按随机数字表法分为2组,对照组(n=100)给予常规治疗+恩格列净,观察组(n=100)在对照组基础上给予活血益肾方。评价2组临床治疗总有效率,比较2组治疗前后尿白蛋白(albium,Alb)、尿β2微球蛋白(β2-microglobulin,β2-MG)、尿微量白蛋白/肌酐(UmAlb/UCr,A/C)、血8-异构前列腺素-F2α(8-iso-prostaglandin F2α,8-iso-PGF2α)、血胱抑素C(cystatin C,CysC)、炎症因子、纤维化指标及主要症状改善情况。结果观察组总有效率90.0%,高于对照组77.0%(χ^(2)=6.133,P=0.013)。治疗后,2组尿Alb、尿β2-MG、尿A/C、血8-iso-PGF2α、血CysC水平[对照组:(17.18±5.69)mg/L、(5.11±1.07)mg/L、(292.85±45.42)mg/g、(15.05±2.21)ng/mL、(0.63±0.09)mg/L;观察组:(8.35±2.76)mg/L、(3.73±1.01)mg/L、(264.38±38.63)mg/g、(9.16±1.27)ng/mL、(0.58±0.04)mg/L]均低于治疗前[对照组:(52.54±13.72)mg/L、(7.49±1.43)mg/L、(328.57±49.72)mg/g、(22.12±3.38)ng/mL、(1.07±0.12)mg/L;观察组:(51.86±12.23)mg/L、(7.55±1.38)mg/L、(323.66±47.84)mg/g、(21.86±3.35)ng/mL、(0.95±0.14)mg/L](P<0.05),且观察组尿Alb、尿β2-MG、尿A/C、血8-iso-PGF2α、血CysC水平[(8.35±2.76)mg/L、(3.73±1.01)mg/L、(264.38±38.63)mg/g、(9.16±1.27)ng/mL、(0.58±0.04)mg/L]均低于对照组[(17.18±5.69)mg/L、(5.11±1.07)mg/L、(292.85±45.42)mg/g、(15.05±2.21)ng/mL、(0.63±0.09)mg/L](P<0.05)。治疗后,2组各项主要症状得分[对照组:(1.67±0.54)分、(1.56±0.49)分、(1.26±0.39)分、(1.13±0.36)分、(1.23±0.39)分、(1.34±0.43)分;观察组:(0.95±0.31)分、(0.84±0.27)分、(0.65±0.19)分、(0.59±0.18)分、(0.72±0.23)分、(0.79±0.25)分]均低于治疗前[对照组:(2.74±0.89)分、(2.85±0.94)分、(2.27±0.74)分、(2.06±0.67)分、(2.17±0.72)分、(2.32±0.76)分;观察组:(2.79±0.92)分、(2.78±0.91)分、(2.34±0.77)分、(2.11±0.69)分、(2.24±0.73)分、(2.27±0.74)分](P<0.05),且观察组各项主要症状得分[(0.95±0.31)分、(0.84±0.27)分、(0.65±0.19)分、(0.59±0.18)分、(0.72±0.23)分、(0.79±0.25)分]均低于对照组[(1.67±0.54)分、(1.56±0.49)分、(1.26±0.39)分、(1.13±0.36)分、(1.23±0.39)分、(1.34±0.43)分](P<0.05)。治疗后,2组肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、C反应蛋白(C-reactive protein,CRP)水平[对照组:(57.95±12.23)ng/L、(18.67±4.11)ng/L、(7.79±2.54)ng/L;观察组:(44.32±11.02)ng/L、(14.85±2.2)ng/L、(5.12±1.68)ng/L]均低于治疗前[对照组:(67.62±10.14)ng/L、(22.24±3.72)ng/L、(10.23±3.38)ng/L;观察组:(66.49±11.82)ng/L、(21.73±4.58)ng/L、(9.58±3.09)ng/L](P<0.05),且观察组TNF-α、IL-6、CRP水平[(44.32±11.02)ng/L、(14.85±2.2)ng/L、(5.12±1.68)ng/L]均低于对照组[(57.95±12.23)ng/L、(18.67±4.11)ng/L、(7.79±2.54)ng/L](P<0.05)。治疗后,2组层粘连蛋白(laminin,LN)、Ⅲ型前胶原(procollagen typeⅢ,PCⅢ)、Ⅳ型胶原(collagen typeⅣ,C-Ⅳ)、透明质酸(hyaluronic acid,HA)[对照组:(101.63±13.04)μg/L、(87.04±16.53)μg/L、(92.89±22.63)μg/L、(137.07±45.63)ng/L;观察组:(76.81±9.38)μg/L、(57.85±14.07)μg/L、(61.52±13.64)μg/L、(121.05±40.34)ng/L]均低于治疗前[对照组:(128.42±16.18)μg/L、(135.17±18.59)μg/L、(130.93±31.52)μg/L、(175.11±52.24)ng/L;观察组:(129.69±18.42)μg/L、(133.83±20.62)μg/L、(128.72±28.11)μg/L、(178.29±51.86)ng/L](P<0.05),且观察组LN、PCⅢ、C-Ⅳ、HA[(76.81±9.38)μg/L、(57.85±14.07)μg/L、(61.52±13.64)μg/L、(121.05±40.34)ng/L]均低于对照组[(101.63±13.04)μg/L、(87.04±16.53)μg/L、(92.89±22.63)μg/L、(137.07±45.63)ng/L](P<0.05)。结论活血益肾方联合恩格列净治疗DKD,有助于调节尿Alb、尿β2-MG、尿A/C、血8-iso-PGF2α、血CysC水平与炎症因子水平,对纤维化指标、主要症状也有一定改善作用,临床治疗总有效率有所提高。

Objective To explore the efficacy of Huoxue Yishen Recipe plus sodium glucose cotransporter 2(SGLT2)inhibitors in the treatment of diabetic kidney disease(DKD).Methods From January 2020 to January 2021,200 hospitalized DKD patients were randomized into two groups.Control group(n=100)received conventional measures plus empagliflozin while study group(n=100)had Huoxue Yishen Recipe on the basis of control group.Total effective rate of two groups was evaluated.And urinary albumin(Alb),urinary β2 microglobulin(β2-MG),urinary microalbumin/creatinine(A/C),blood 8-iso-prostaglandin-F2α(8-iso-PGF2α),cystatin C(CysC),inflammatory factors,fibrotic indices and improvement of main symptoms were compared between two groups before and after treatment.Results Total effective rate was higher in study group than in control group[90.0%vs 77.0%,χ^(2)=6.133,P=0.013].After treatment,the levels of urinary Alb,urinary β2-MG,urinary A/C,blood 8-iso-PGF2α and blood Cys-C[control group:(17.18±5.69)mg/L,(5.11±1.07)mg/L,(292.85±45.42)mg/g,(15.05±2.21)ng/mL,(0.63±0.09)mg/L;study group:(8.35±2.76)mg/L,(3.73±1.01)mg/L,(264.38±38.63)mg/g,(9.16±1.27)ng/mL,(0.58±0.04)mg/L]were lower than before treatment[control group:(52.54±13.72)mg/L,(7.49±1.43)mg/L,(328.57±49.72)mg/g,(22.12±3.38)ng/mL,(1.07±0.12)mg/L];study group:[(51.86±12.23)mg/L,(7.55±1.38)mg/L,(323.66±47.84)mg/g,(21.86±3.35)ng/mL,(0.95±0.14)mg/L](P<0.05),the levels of urinary Alb,urinaryβ2-MG,urinary A/C,blood 8-iso-PGF2αand blood CysC[(8.35±2.76)mg/L,(3.73±1.01)mg/L,(264.38±38.63)mg/g,(9.16±1.27)ng/mL,(0.58±0.04)mg/L]were lower in study group than those in control group[(17.18±5.69)mg/L,(5.11±1.07)mg/L,(292.85±45.42)mg/g,(15.05±2.21)ng/mL,(0.63±0.09)mg/L](P<0.05).After treatment,the scores of main symptoms of two groups[control group:(1.67±0.54)points,(1.56±0.49)points,(1.26±0.39)points,(1.13±0.36)points,(1.23±0.39)points,(1.34±0.43)points;study group:(0.95±0.31)points,(0.84±0.27)points,(0.65±0.19)points,(0.59±0.18)points,(0.72±0.23)points,(0.79±0.25)points]were lower than those before treatment[control group:(2.74±0.89)points,(2.85±0.94)points,(2.27±0.74)points,(2.06±0.67)points,(2.17±0.72)points,(2.32±0.76)points;study group:(2.79±0.92)points,(2.78±0.91)points,(2.34±0.77)points,(2.11±0.69)points,(2.24±0.73)points,(2.27±0.74)points](P<0.05)and the points of main symptoms of study group[(0.95±0.31)points,(0.84±0.27)points,(0.65±0.19)points,(0.59±0.18)points,(0.72±0.23)points,(0.79±0.25)points]were lower than those of control group[(1.67±0.54)points,(1.56±0.49)points,(1.26±0.39)points,(1.13±0.36)points,(1.23±0.39)points,(1.34±0.43)points](P<0.05).After treatment,the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and Creactive protein(CRP)[control group:(57.95±12.23)ng/L,(18.67±4.11)ng/L,(7.79±2.54)ng/L;study group:(44.32±11.02)ng/L,(14.85±2.2)ng/L,(5.12±1.68)ng/L]were lower than before treatment[control group:(67.62±10.14)ng/L,(22.24±3.72)ng/L,(10.23±3.38)ng/L;study group:(66.49±11.82)ng/L,(21.73±4.58)ng/L,(9.58±3.09)ng/L](P<0.05)and the levels of TNF-α,IL-6,and CRP[(44.32±11.02)ng/L,(14.85±2.2)ng/L,(5.12±1.68)ng/L]were lower in study group than those in control group[(57.95±12.23)ng/L,(18.67±4.11)ng/L,(7.79±2.54)ng/L](P<0.05).After treatment,laminin(LN),typeⅢprocollagen(PCⅢ),typeⅣcollagen(C-Ⅳ)and hyaluronic acid(HA)[control group:(101.63±13.04)μg/L,(87.04±16.53)μg/L,(92.89±22.63)μg/L,(137.07±45.63)ng/L;study group:(76.81±9.38)μg/L,(57.85±14.07)μg/L,(61.52±13.64)μg/L,(121.05±40.34)ng/L]were lower than before treatment[control group:(128.42±16.18)μg/L,(135.17±18.59)μg/L,(130.93±31.52)μg/L,(175.11±52.24)ng/L;study group:(129.69±18.42)μg/L,(133.83±20.62)μg/L,(128.72±28.11)μg/L,(178.29±51.86)ng/L](P<0.05)and LN,PCⅢ,C-Ⅳ and HA[(76.81±9.38)μg/L,(57.85±14.07)μg/L,(61.52±13.64)μg/L,(121.05±40.34)ng/L]were lower in study group than those in control group[(101.63±13.04)μg/L,(87.04±16.53)μg/L,(92.89±22.63)μg/L,(137.07±45.63)ng/L](P<0.05).Conclusion Huoxue Yishen Recipe plus empagliflozin in the treatment of DKD may regulate urinary Alb,urinaryβ2-MG,urinary A/C,blood 8-iso-PGF2α,blood CysC levels and inflammatory factor levels and improve fibrotic indices and main symptoms and enhance total effective rates.