参芪地黄汤加减治疗气阴两虚型糖尿病肾病疗效观察及对肠道菌群和炎症因子的影响

Observation on the Curative Effect of Modified Shenqi Dihuang Decoction in Treating Diabetic Kidney Disease with Deficiency of Both Qi and Yin and Its Effects on Intestinal Flora and Inflammation Factors

目的观察参芪地黄汤加减辨治气阴两虚型糖尿病肾病(DKD)的临床疗效及对肠道菌群和炎症因子的调节效果。方法将160例DKD患者随机分为对照组和观察组,每组各80例。2组患者均采用控制血糖、血压,纠正脂质代谢紊乱等综合措施干预,对照组同时口服氯沙坦钾片治疗;观察组在对照组治疗的基础上给予参芪地黄汤加减治疗,疗程为3个月。观察2组患者治疗前后尿蛋白指标、肾功能指标、血糖指标、炎症相关因子和肠道菌群的水平变化,并评价2组患者的中医证候积分和临床疗效。结果 (1)观察组脱落2例,违背方案剔除3例,共完成研究75例;对照组脱落4例,违背方案剔除3例,共完成研究73例。(2)观察组总有效率为94.67%(71/75),对照组为83.56%(61/73),观察组总有效率高于对照组(χ^(2)=4.731,P <0.05)。(3)2组治疗后的24 h尿蛋白定量(24 h UAE)、尿白蛋白/肌酐比值(ACR)、尿微量白蛋白(mAlb)和尿β2微球蛋白(β2-MG)水平均较治疗前明显降低(P <0.01),且观察组各尿蛋白指标水平低于对照组(P <0.01)。(4)治疗后,2组血清肌酐(SCr)、肾损伤分子1(KIM-1)、胱抑素C(CysC)水平下降(P <0.01),肾小球滤过率(eGFR)升高(P <0.01),且治疗后观察组各肾功能指标改善优于对照组(P <0.01)。(5)治疗后,2组患者白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和转化生长因子β1(TGF-β1)水平明显下降(P <0.01),且治疗后观察组各炎症相关因子指标均低于对照组(P <0.01)。(6)治疗后,2组空腹血糖(FGP)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)和中医证候积分明显下降(P <0.01),且治疗后观察组HbA1c和中医证候积分低于对照组(P <0.01)。(7)2组患者治疗后的拟杆菌、双歧杆菌、乳酸杆菌数量增加(P <0.05,P <0.01),肠杆菌、肠球菌、酵母菌减少(P <0.05,P <0.01),且治疗后观察组拟杆菌、双歧杆菌、乳酸杆菌数量多于对照组(P <0.01),肠杆菌、肠球菌、酵母菌少于对照组(P <0.01)。结论参芪地黄汤加减治疗DKD气阴两虚证疗效显著,既可改善中医症状,减轻蛋白尿,保护肾功能,还能减轻患者慢性微炎症状态和恢复肠道菌群平衡,临床疗效优于单纯西医治疗。

Objective To observe the curative effect of modified Shenqi Dihuang decoction in the treatment of diabetic kidney disease(DKD)with deficiency of qi and yin,and to study the regulatory effect on intestinal flora and inflammatory factors. Methods Patients(160 cases) with DKD were randomly divided into control group and observation group, 80 cases in each group. All the patients were given the comprehensive intervention, such as controlling blood sugar and blood pressure,correcting lipid metabolism disorder,and patients in control group were treated with losartan potassium tablets. Based on the treatment of control group, patients in observation group additionally received the treatment of Shenqi Dihuang decoction. The treatment was continued for 3 months. The changes of urine protein index,kidney function index,blood sugar index,inflammation-related factors and level of intestinal flora in two groups were observed before and after treatment. Traditional Chinese medicine syndrome scores and clinical efficacy of the two groups were evaluated. Results(1)In the observation group,two cases were lost,three cases were eliminated from the plan,and seventy-five cases were completed. In the control group,four cases were lost,three cases were eliminated due to the violation of the study,and seventy-three cases were completed.(2)The total effective rate of the observation group was 94.67%(71/75),which was better than that of 83.56%(61/73)in the control group(χ^(2)= 4.731,P < 0.05).(3)The levels of 24 h urine albumin excretion(24 h UAE),urine albumin-to-creatinine ratio(ACR), urine microalbumin(mAlb), urine β2 microglobulin(β2-MG)were significantly lower than those before treatment in both groups(P < 0.01). Besides, the urine protein level in observation group was lower than that in control group(P < 0.01).(4)The levels of serum creatinine(SCr),kidney injury molecule 1(KIM-1)and cystatin C(CysC)in two groups were decreased(P < 0.01). However,the glomerular filtration rate(eGFR)was increased(P < 0.01). After therapy,the renal function indexes in observation group were significantly favorable compared with those in control group(P < 0.01).(5)The levels of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α)and transforming growth factor β1(TGF-β1)in both groups were significantly decreased(P < 0.01). After treatment,the inflammation-related factors indicators of the observation group were lower than those of the control group(P < 0.01).(6)After treatment,the fasting blood glucose(FGP),2 h postprandial blood glucose(2 h PG),glycosylated hemoglobin(HbA1 c)and TCM syndrome scores of the two groups decreased significantly(P < 0.01). And the scores of HbA1 c and TCM syndrome in the observation group were lower than those in the control group(P < 0.01).(7) The numbers of bacteroides, bifidobacteria and lactobacillus in the two groups increased(P < 0.05,P < 0.01),but the numbers of enterobacter,enterococcus and yeast in the two groups decreased(P < 0.05,P < 0.01). After treatment,the observation group had higher numbers of bacteroides,bifidobacteria and lactobacillus than the control group(P < 0.01). Compared with the control group,there were decreases in enterobacteria, enterococci and yeasts in observation group(P < 0.01). Conclusion Modified Shenqi Dihuang decoction has good curative effect on treating DKD with deficiency of qi and yin. It can improve traditional Chinese medicine symptom,reduce proteinuria,protect renal function,restore the balance of intestinal flora,and alleviate chronic inflammation,which is better than western medicine.