硫辛酸对1型糖尿病大鼠肾脏病变的影响及机制初探  

The effect and mechanism of lipoic acid on diabetic nephropathy in type 1 diabetic rats

作　　者：王星 龙冬梅 郭楠 WANG Xing;LONG Dongmei;GUO Nan(Clinical Pharmacy Teaching and Research Department,School of Pharmacy,North Sichuan Medical College,Nanchong 637100,China;College of Modern Agricultural Technology,Nanchong Vocational and Technical College,Nanchong 637131,China;Department of Pharmacy,Minhang Hospital,Fudan University,Shanghai 201199,China)

机构地区：[1]川北医学院药学院临床药学教研室,四川南充637100 [2]南充职业技术学院现代农业技术学院,四川南充637131 [3]复旦大学附属闵行医院药剂科,上海201199

出　　处：《药学研究》2025年第3期224-230,240,共8页Journal of Pharmaceutical Research

基　　金：四川省自然科学基金青年基金项目(No.2023NSFSC1676);南充市科技计划项目(No.23YYJCYJ0026);川北医学院杰出青年项目(No.CBY23-JQ03);川北医学院博士科研启动基金项目(No.CBY21-QD16);上海市启明星扬帆专项项目(No.22YF1439800)。

摘　　要：目的研究硫辛酸(ALA)对1型糖尿病肾病(DN)大鼠的影响并初步探讨其作用机制。方法链脲佐菌素(STZ)成功诱导SD大鼠形成1型DN后,将其随机分为模型组和ALA(100 mg·kg^(-1))治疗组,另取10只鼠龄相当的SD大鼠为正常对照组,灌胃给药12周。实验期间测定大鼠体质量、随机血糖、禁食血糖、糖化血红蛋白、摄食量和饮水量,进行口服葡萄糖耐量实验,用代谢笼收集尿液;处死大鼠后,留取血清和肾脏,测定血清和尿液中肾脏病变相关指标,检测血清中脂质代谢、氧化应激、炎症反应相关指标;测定肾脏中氧化应激相关指标以及蛋白表达。结果ALA对糖尿病肾病大鼠血糖基本代谢指标无影响,但能改善糖耐量异常;ALA可减少糖尿病肾病大鼠的尿量,降低尿液中葡萄糖、尿微量白蛋白、β2微球蛋白含量和ACR指数,抑制N-乙酰氨基葡萄糖苷酶活性;ALA降低血清中肌酐、尿素氮含量及肾脏指数,明显改善糖尿病肾病大鼠肾脏病理形态异常;ALA改善糖尿病肾病大鼠血脂紊乱,增强血清及肾脏中抗氧化酶活性,降低丙二醛(MDA)含量,明显降低血清中促炎因子水平并增加抗炎因子含量;ALA上调糖尿病肾病大鼠肾脏中蛋白核因子E2相关因子(Nrf2)和血红素加氧酶-1(HO-1)表达,抑制肾脏中蛋白胞质蛋白伴侣分子1(Keap1)及磷酸化核因子κ轻链增强活化B细胞(NF-κB)表达。结论ALA可能通过调节Nrf2/Keap1和NF-κB信号通路,从而抑制糖尿病大鼠肾脏氧化应激受损和炎症反应,进而改善1型DN。Objective To study the effect of lipoic acid(ALA)on type 1 diabetic nephropathy(DN)rats and explore its mechanism.Methods After successfully inducing type 1 DN in SD rats with STZ,the model rats were randomly divided into model group and ALA(100 mg·kg^(-1))treatment group,and another 10 normal SD rats of the same age were taken as normal control group and given orally ALA for 12 weeks.During the experiment,the body weights of the rats,random blood glucose,fasting blood glucose,glycosylated hemoglobin,food intake and water consumption were measured,the oral glucose tolerance test was carried out,and the urine was collected with metabolic cage.After the rats were killed,the serum and kidneys were taken.The indexes related to renal diseases in serum and urine were measured,and the indexes related to lipid metabolism,oxidative stress and inflammatory reaction in serum were detected.The related indexes of oxidative stress and protein expression in kidney were examined.Results ALA had no effect on the basic metabolic indexes in diabetic nephropathy rats,but it can attenuate the abnormal glucose tolerance.ALA significantly reduced the urine volume,the levels of urine glucose,urinary microalbumin,β2 microglobulin and ACR index in diabetic nephropathy rats,and inhibited the activity of N-acetylglucosaminidase.ALA decreased the contents of creatinine,blood urea nitrogen in serum,the renal index,and markedly alleviated renal pathological abnormalities in diabetic nephropathy rats.ALA relieved the dyslipidemia,enhanced the activities of antioxidant enzymes in serum and kidney,reduced the content of malondialdehyde(MDA),noticeably reduced the levels of proinflammatory factors and increased the content of anti-inflammatory factors in serum.ALA upregulated the expression of protein nuclear factor E2 related factors(Nrf2)and heme oxygenase-1(HO-1),and inhibited the expression of protein kelch-like ECH-associated protein-1(Keap1)and phosphorylated nuclear factor-kappaB(NF-κB)in kidney of the diabetic rats.Conclusion ALA may re

关 键 词：硫辛酸 糖尿病肾病 氧化应激 炎症反应 Nrf2/Keap1信号通路 

分 类 号：R965[医药卫生—药理学]