真武汤合五皮饮加减对糖尿病肾病患者肾脏纤维化、肾小管氧化损伤和PI3K/Akt/NF-κB信号通路的影响

Effects of Modified Zhenwu Decoction Combined with Wupiyin on Renal Fibrosis,Renal Tubule Oxidative Damage and PI3K/Akt/NF-κB Signaling Pathway in Patients with Diabetic Nephropathy

目的:观察真武汤合五皮饮加减对糖尿病肾病患者肾脏纤维化、肾小管氧化损伤和磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/核因子κB(NF-κB)信号通路的影响。方法:选择2021年2月至2023年2月该院收治的糖尿病肾病患者100例,所有患者均采用随机数字表法分组。基础干预组50例患者(脱落3例,最终纳入47例)给予常规西医治疗,观察组50例患者(脱落2例,最终纳入48例)在基础干预组的基础上给予真武汤合五皮饮加减治疗。治疗前后对两组患者进行中医证候评价,检测谷胱甘肽过氧化物酶(GSH-Px)、结缔组织生长因子(CTGF)、活性氧(ROS)、糖化血红蛋白(HbA1c)、透明质酸(HA)、层粘连蛋白(LN)、尿白蛋白排泄率(UAE)、尿β2-微球蛋白(β2-MG)水平及24 h尿蛋白定量,PI3K、Akt和NF-κB的mRNA表达水平,比较两组患者的临床疗效。结果:观察组患者的总有效率较基础干预组明显升高[97.92%(47/48)vs. 82.98%(39/47)],差异有统计学意义(P<0.05)。治疗后,观察组患者神疲畏寒、尿浊、腰膝酸冷、肢体浮肿、下肢尤甚、小便清长或短少、面色白光白、夜尿增多及五更泄泻的评分较基础干预组明显降低,差异均有统计学意义(P<0.05)。治疗后,观察组患者的HbA1c、UAE和24 h尿蛋白定量较基础干预组明显降低,GSH-Px水平较基础干预组明显升高,ROS、β2-MG水平较基础干预组明显降低,NF-κB mRNA表达水平较基础干预组明显降低,PI3K、Akt mRNA表达水平较基础干预组明显升高,CTGF、HA和LN水平较基础干预组明显降低,差异均有统计学意义(P<0.05)。结论:真武汤合五皮饮加减用于糖尿病肾病患者,可调节PI3K/Akt/NF-κB信号通路,减少肾小管氧化损伤,改善肾脏纤维化病情,调节HbA1c、UAE和24 h尿蛋白定量,提高临床疗效。

OBJECTIVE:To observe the effects of modified Zhenwu decoction and Wupiyin on renal fibrosis,renal tubule oxidative damage and lipoyl inositol 3 kinase(PI3K)/threonine kinase(Akt)/nuclear factorκB(NF-κB)signaling pathway in patients with diabetic nephropathy.METHODS:A total of 100 patients with diabetic nephropathy admitted into this hospital from Feb.2021 to Feb.2023 were selected and grouped via random number table method.The 50 cases in the basic intervention group(3 cases lost,47 cases was eventually enrolled)were given conventional Western medicine treatment,while the 50 cases in the observation group(2 cases lost,48 cases eventually enrolled)were given modified Zhenwu decoction combined with Wupiyin based on the basic intervention group.The traditional Chinese medicine(TCM)syndrome evaluation was conducted,the glutathione peroxidase(GSH-Px),connective tissue growth factor(CTGF),reactive oxygen species(ROS),glycosylated hemoglobin(HbA1c),hyaluronic acid(HA),laminin(LN),urinary albumin excretion rate(UAE),urinaryβ2-microglobulin(β2-MG)and 24 h urinary protein quantitation levels,the mRNA levels of PI3K,Akt and NF-κB were detected,the clinical efficacy were compared between two groups.RESULTS:The total effective rate of the observation group was significantly higher than that of the basic intervention group[97.92%(47/48)vs.82.98%(39/47)],with statistically significant difference(P<0.05).After treatment,TCM syndrome scores of fatigue and cold intolerance,turbid urine,soreness and weakness of waist and knees,limbs especially lower limbs edema,abnormal urination,pale complexion,increased nocturnal urination and morning diarrhea of the observation group were significantly lower than those of the basic intervention group,with statistically significant differences(P<0.05).After treatment,the HbA 1c,UAE and 24 h urinary protein quantitation were significantly lower,the GSH-Px content was significantly higher,the ROS andβ2-MG contents were significantly lower,the NF-κB mRNA level was significantly lower,the PI3K and Akt mRNA levels were significantly higher,the CTGF,HA and LN contents were significantly lower in the observation group than those in the basic intervention group,with statistically significant differences(P<0.05).CONCLUSIONS:The combined application of modified Zhenwu decoction and Wupiyin for patients with diabetic nephropathy can regulate PI3K/Akt/NF-κB signaling pathway,reduce renal tubule oxidative injury,improve renal fibrosis,regulate HbA 1c,UAE and 24 h urinary protein quantitation,and promote clinical efficacy.