水陆地黄调控AMPK/Nox4信号通路对糖尿病肾病模型大鼠的影响  

Effects of Shuilu Dihuang Capsules on AMPK/Nox4 Signaling Pathway in Diabetic Nephropathy Model Rats

作　　者：郑婷娜 马常娥 ZHENG Tingna;MA Chang'e(Modern Rehabilitation Medical Care College of Shanxi Energy Institute,Xi'an,Shaanxi,China 710000;Zhangye People's Hospital Affiliated to Hexi University,Zhangye,Gansu,China 734000)

机构地区：[1]陕西能源职业技术学院现代康养学院,陕西西安710000 [2]河西学院附属张掖人民医院,甘肃张掖734000

出　　处：《中国药业》2025年第8期55-60,共6页China Pharmaceuticals

基　　金：甘肃省卫生厅医药科研计划课题[1292GS2019B57]。

摘　　要：目的探讨水陆地黄胶囊对糖尿病肾病(DN)模型大鼠的影响及其对腺苷酸活化蛋白激酶(AMPK)/烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(Nox4)信号通路的调控机制。方法将SD大鼠随机分为空白对照组(等体积生理盐水灌胃)、模型组(等体积生理盐水灌胃)、水陆地黄组(6 g/kg灌胃)、厄贝沙坦组(1.04 g/kg灌胃)、水陆地黄+Compound C组(6 g/kg灌胃+250μg/kg AMPK抑制剂Compound C尾静脉一次性注射)。予高脂高糖饮食喂养6周,后一次性腹腔注射链脲佐菌素溶液55 mg/kg以复制DN大鼠模型。空白对照组正常饲养6周后一次性腹腔注射等体积柠檬酸钠缓冲液。建模成功后,灌胃相应药物或生理盐水,每天1次,连续8周。检测大鼠空腹血糖(FBG)及尿液中24 h尿蛋白总量(24 h-UTP);苏木精-伊红(HE)染色,检测肝肾组织病理形态变化;采用酶联免疫吸附法检测大鼠血清肌酐(SCr)、尿素氮(BUN)、糖化血红蛋白(HbA_(1C))水平;检测大鼠肾组织中丙二醛(MDA)和超氧化物歧化酶(SOD)水平,Western blot法检测肾组织中AMPK、p-AMPK、Nox4、转化生长因子β_(1)(TGF-β_(1))蛋白表达水平。结果水陆地黄组和厄贝沙坦组大鼠肝脏组织纤维化及脂肪变性程度较空白对照组明显减轻;肾小球肥大,系膜细胞、系膜基质细胞增生,肾小管上皮细胞呈空泡样病变,血管淤血、扩张程度较空白对照组明显减轻;模型组与水陆地黄+Compound C组肝脏、肾脏病理程度相当。与模型组比较,水陆地黄组和厄贝沙坦组大鼠肾组织中SOD水平和p-AMPK/AMPK显著升高,FBG,24 h-UTP,SCr、BUN、HbA_(1C),肾组织中MDA水平和Nox4、TGF-β_(1)蛋白表达水平均显著降低(P<0.05);与水陆地黄组比较,水陆地黄+Compound C组大鼠肾组织中SOD水平和p-AMPK/AMPK显著降低,FBG,24 h-UTP,SCr、BUN、HbA_(1C),肾组织中MDA水平及Nox4、TGF-β_(1)蛋白表达水平均显著升高(P<0.05)。结论水陆地黄胶囊可能通过激活AMPK/Nox4信号通路减Objective To investigate the effect of Shuilu Dihuang Capsules on diabetic nephropathy(DN)model rats and its regulatory mechanism on AMP-activated protein kinase(AMPK)/nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4)signaling pathway.Methods SD rats were randomly divided into blank control group(intragastric administration with an equal volume of normal saline),model group(intragastric administration with an equal volume of normal saline),Shuilu Dihuang group(intragastric administration of 6 g/kg),irbesartan group(intragastric administration of 1.04 g/kg),Shuilu Dihuang+Compound C group(intragastric administration of 6 g/kg+250μg/kg AMPK inhibitor Compound C by tail vein injection).After 6 weeks of high-fat and high-sugar diet feeding,subsequently,a single intraperitoneal injection of streptozotocin solution(55 mg/kg)was administered to replicate the DN rat model.After 6 weeks of normal feeding,the blank control group was intraperitoneally injected with an equal volume of sodium citrate buffer solution.After successful modeling,the corresponding drugs or normal saline were intragastrically administered once a day for 8 weeks.Fasting blood glucose(FBG)and 24 hours urinary protein(24 h-UTP)were detected.Hematoxylin-eosin(HE)staining was used to detect the pathological changes of liver and kidney tissues.The levels of serum creatinine(SCr),urea nitrogen(BUN)and glycosylated hemoglobin(HbA_(1C))were detected by enzyme-linked immunosorbent assay.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in renal tissue of rats were detected,and the protein expression levels of AMPK,p-AMPK,Nox4 and transforming growth factor-β_(1)(TGF-β_(1))in renal tissue were detected by Western blot.Results Compared to the blank control group,the degree of liver fibrosis and steatosis,glomerular hypertrophy,proliferation of mesangial cells and mesangial stromal cells,renal tubular epithelial cells exhibited vacuolar degeneration,congestion and degree of dilation of blood vessel in Shuilu Dihuang group and irbesar

关 键 词：水陆地黄胶囊 糖尿病肾病 AMPK/Nox4信号通路 氧化应激 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]