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1.河南中医药大学第一附属医院儿科医院,郑州 450000
2.河南中医药大学儿科医学院,郑州 450046
梁 爽,Email:liangshuang202209@163.com,研究方向:中医药防治小儿肾脏疾病研究。
宋纯东,Email:scd670918@126.com。
收稿:2025-09-12,
修回:2026-01-06,
录用:2026-01-12,
纸质出版:2026-03-02
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梁爽, 宋纯东, 贾评评, 等. 益气养阴活血方通过调节AHR/NF-κB/Nrf2轴改善膜性肾病作用机制研究[J/OL]. 重庆医科大学学报, 2026,1-7.
Liang Shuang,Song Chundong,Jia Pingping,et al.Mechanism of action of Yiqi Yangyin Huoxue prescription in improving membranous nephropathy by regulating the aromatic hydrocarbon receptor/nuclear factor kappa B/nuclear factor erythroid 2-related factor 2 axis[J].Journal of Chongqing Medical University,
梁爽, 宋纯东, 贾评评, 等. 益气养阴活血方通过调节AHR/NF-κB/Nrf2轴改善膜性肾病作用机制研究[J/OL]. 重庆医科大学学报, 2026,1-7. DOI:
Liang Shuang,Song Chundong,Jia Pingping,et al.Mechanism of action of Yiqi Yangyin Huoxue prescription in improving membranous nephropathy by regulating the aromatic hydrocarbon receptor/nuclear factor kappa B/nuclear factor erythroid 2-related factor 2 axis[J].Journal of Chongqing Medical University, DOI:10.13406/j.cnki.cyxb..
目的
2
探讨益气养阴活血方通过调节芳烃受体(aryl hydrocarbon receptor,AHR)/核因子κB(nuclear factor kappa B,NF-κB)/核因子红细胞2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)轴改善膜性肾病(membranous nephropathy,MN)大鼠肾损伤的作用机制。
方法
2
将42只SPF级雄性SD大鼠随机选取6只作为空白组,其余大鼠通过单次尾静脉注射羊抗大鼠Fx1A血清构建MN模型。造模成功后,将36只成模大鼠随机分为模型组、贝那普利组(10 mg/kg)以及益气养阴活血方低、高剂量组(11.0、22.0 g/kg)。连续给药6 周,检测大鼠24 h尿蛋白定量(urinary protein quantity,UTP)、血尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,SCr)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、白蛋白(albumin,ALB)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平;苏木素-伊红(hematoxylin-eosin,HE)、基底膜六胺银(periodic acid-silver methenamine,PASM)染色观察大鼠肾组织病理形态;蛋白免疫印迹法(Western blot,WB)和实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,RT-qPCR)检测肾组织中AHR、NF-κB、Nrf2通路相关蛋白及mRNA的表达。
结果
2
与空白组相比,模型组大鼠24 h UTP、血清TG、TC、BUN、SCr水平显著升高,ALB水平显著降低(
P
<
0.01);肾脏病理损伤明显;肾组织AHR、NF-κB p65、COX-2蛋白表达显著升高(
P
<
0.01),Nrf2、HO-1蛋白及mRNA表达显著降低(
P
<
0.01)。与模型组相比,各治疗组大鼠24 h UTP、血清TG、TC、BUN、SCr水平显著降低(
P
<
0.01),ALB水平显著升高(
P
<
0.01);各治疗组肾脏病理损伤均得到明显改善;肾组织AHR、NF-κB p65、COX-2蛋白表达显著降低(
P
<
0.01),Nrf2、HO-1蛋白及mRNA表达显著升高(
P
<
0.01)。
结论
2
益气养阴活血方可能通过调控AHR/NF-κB/Nrf2轴,缓解肾组织氧化应激,抑制炎症,进而保护肾脏及延缓疾病进展。
Objective
2
To investigate the mechanism of action of Yiqi Yangyin Huoxue prescription in improving renal injury in rats with membranous nephropathy(MN) by regulating the aromatic hydrocarbon receptor(AHR)/nuclear factor kappa B(NF-κB)/nuclear factor erythroid 2-related factor 2(Nrf2) axis.
Methods
2
A total of 42 specific pathogen-free male Sprague-Dawley rats were used,among which 6 rats were randomly selected as the blank group,and the remaining 36 rats were given a single injection of sheep anti-rat Fx1A serum via the caudal vein to establish a model of MN. After successful modeling,the 36 rats for modeling were randomly divided into model group,benazepril group(10 mg/kg),equal-dose Yiqi Yangyin Huoxue prescription group(11.0 g/kg),and high-dose Yiqi Yangyin Huoxue prescription group(22.0 g/kg). After administration for 6 consecutive weeks,the rats were measured for 24-hour urinary total protein(24h-UTP),blood urea nitrogen(BUN),serum creatinine(SCr),triglyceride(TG),total cholesterol(TC),albumin(ALB),alanine aminotransferase(ALT),and aspartate aminotransferase(AST); HE staining and basement membrane periodic acid-silver methenamine(PASM) staining were used to observe the pathological morphology of rat renal tissue; Western blot and RT-qPCR were used to measure the protein and mRNA expression levels of AHR/NF-κB/Nrf2 pathway-related proteins in renal tissue.
Results
2
Compared with the normal group,the model group had significant increases in 24h-UTP and the serum levels of TG,TC,BUN,and SCr and a significant reduction in the level of ALB(
P
<
0.01),with marked renal pathological injury,as well as significant increases in the protein expression levels of AHR,NF-κB p65,and COX-2 in renal tissue(
P
<
0.01) and significant reductions in the protein and mRNA expression levels of Nrf2 and HO-1 in renal tissue(
P
<
0.01). Compared with the model group,each treatment group had significant reductions in 24h-UTP and the serum levels of TG,TC,BUN,and SCr(
P
<
0.01),a significant increase in the level of ALB(
P
<
0.01),a significant improvement in renal pathological injury,significant reductions in the protein expression levels of AHR,NF-κB p65,and COX-2 in renal tissue(
P
<
0.01),and significant increases in the protein and mRNA expression levels of Nrf2 and HO-1 in renal tissue(
P
<
0.01).
Conclusion
2
Yiqi Yangyin Huoxue prescription can alleviate oxidative stress in renal tissue,inhibit inflammation,protect the kidneys,and delay disease progression by regulating the AHR/NF-κB/Nrf2 axis.
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