川陈皮素对糖尿病肾病大鼠AMPK和eNOS表达的影响研究  

The effect of nobiletin on the expression of AMPK signaling pathway-related proteins in rats with diabetic nephropathy

作　　者：武俊紫 胡冬雄 赵微 贾亚敏[2] 和凤军 杨榆青 WU Junzi;HU Dongxiong;ZHAO Wei;JIA Yamin;HE Fengjun;YANG Yuqing(College of Basic Medicine,Yunnan University of Chinese Medicine,Kunming650504,China;School of Hydro Science&Engineering,Taiyuan University of Technology,Taiyuan030024,Shanxi,China)

机构地区：[1]云南中医药大学基础医学院,云南昆明650504 [2]太原理工大学水利科学与工程学院,山西太原030024

出　　处：《西部医学》2019年第11期1657-1662,共6页Medical Journal of West China

基　　金：国家自然科学基金面上项目(81160492)

摘　　要：目的观察川陈皮素对糖尿病肾病大鼠的治疗作用,并从腺苷酸蛋白活化激酶(AMPK)和内皮型一氧化氮酶(eNOS)途径探讨其作用机理。方法采用高脂高糖饲料喂养+链脲佐菌素(STZ)腹腔注射复制2型糖尿病肾脏损害大鼠模型,模型构建成功后,将其随机分为正常组、模型组、贝那普利干预组以及川陈皮素低、中和高剂量治疗组(n=20)。实验中密切监测大鼠一般情况,治疗期结束后收集尿液检测24h蛋白尿,收集血液检测肾功能指标、抗氧化指标,收集肾脏观察肾脏病理学,同时检测肾脏组织中AMPK及eNOS蛋白和mRNA的表达结果。结果正常组肾小球正常,无明显病理特征;模型组出现肾小球增大,系膜和肾间质纤维组织增生;贝那普利组和川陈皮素三个剂量组相较于模型组明显减轻。与正常组相比,模型组24h尿蛋白定量、UREA、CREA和MDA明显升高(P<0.05);SOD和GSH明显降低(P<0.05),与模型组相比,贝那普利和川陈皮素三个剂量组24h尿蛋白定量、UREA、CREA和MDA明显降低(P<0.05),SOD和GSH明显升高(P<0.05)。与正常组相比,模型组p-AMPK、AMPK和eNOS蛋白和mRNA表达均明显降低(P<0.05);与模型组相比,贝那普利组和川陈皮素低、中和高剂量组AMPK和eNOS蛋白和mRNA表达明显升高(P<0.05)。结论川陈皮素可保护肾功能,提高血清和肾脏抗氧化指标,同时增加AMPK和eNOS蛋白和mRNA表达,最终保护糖尿病肾脏损害。Objective To establish diabetic kidney damage model, observe the therapeutic effect of nobiletin and analyze its mechanism from adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK) pathway. Methods The type 2 diabetes mellitus with renal damage rats model was built with high-fat and high-sugar diet for 1 month+streptozotocin(STZ). After successful construct model, Rats were randomly divided into normal group, model group, benazepril intervention group and the low-, medium-, high-dose nobiletin treatment group(n=20). After the end of the treatment, their urine was collected to detect 24 h proteinuria. The blood was collected for detect renal function index, antioxidant index. The kidney was collected for observed the renal pathology, and the expression of protein and mRNA of AMPK and eNOS. Results Renal pathology could be seen it was normal and no obvious pathological features in normal group. In the model group, it showed obvious glomerular enlargement, mesangial and renal interstitial fibrous. They were improved in the beneloperil group and nobiletin three dose groups. Compared with the normal group, the 24-hour urine protein, UREA, CREA and MDA in the model group were significantly increased(P<0.05) and SOD and GSH were significantly low(P<0.05). The 24 h urine protein, UREA, CREA and MDA in the model group were significantly lower that in the benazepril group and three dose nobiletin groups(P<0.05), and SOD and GSH were significantly increased(P<0.05). Compared with the normal group, the expression of p-AMPK, AMPK, eNOS protein and mRNA in the model group were significantly decreased(P<0.05). Compared with the model group, the above indexes in the benazepril and low, medium and high dose nobiletin groups were significantly increased(P<0.05).Conclusion Nobiletin could protect kidney function, increase serum and kidney antioxidant index, increase eAMPK and eNOS protein and mRNA expression and protect kidney damage.

关 键 词：川陈皮素 糖尿病肾病 氧化应激 腺苷酸蛋白活化激酶 内皮型一氧化氮合酶 

分 类 号：R285.5[医药卫生—中药学] R587.1[医药卫生—中医学]