柚皮素对糖尿病肾病大鼠肾脏损伤的保护作用及机制探讨  

Protective effect and mechanism of naringenin on renal injury in rats with diabetic nephropathy

作　　者：贾冉 李文建[2] 李易明[2] 贾兴莉 石坤治 申琪 魏建华 JIA Ran;LI Wenjian;LI Yiming;JIA Xingli;SHI Kunzhi;SHEN Qi;WEI Jianhua(The People’s Hospital of Zhaoxian County, Zhaoxian 051530, Hebei, China;Hebei Medical University, Shijiazhuang 050031, Hebei, China)

机构地区：[1]河北省赵县人民医院,河北赵县051530 [2]河北医科大学,河北石家庄050031

出　　处：《现代中西医结合杂志》2019年第19期2072-2077,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

摘　　要：目的研究柚皮素对糖尿病肾病大鼠肾脏损伤的保护作用及其相关机制。方法将20只SPF级SD大鼠按照随机原则分为空白组、模型组、柚皮素低剂量组、柚皮素高剂量组,每组5只。除空白组外,其余组给予高脂饲料和1%链脲佐菌素60mg/kg腹腔注射制备糖尿病肾病模型。确认糖尿病肾病造模成功后,柚皮素低剂量组和柚皮素高剂量组每天分别给予柚皮素50mg/kg、100mg/kg灌胃,空白组、模型组每天灌胃等量生理盐水,均1次/d,持续4周。灌胃结束后留取血清标本用于检测血糖、尿素氮、肌酐水平;取肾组织,应用流式细胞术检测各组大鼠肾细胞凋亡情况,应用免疫组织化学法检测肾组织中Bax和Caspase-3蛋白表达情况,实时定量PCR法检测肾组织中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)mRNA表达情况,采用分光光度计检测肾组织中超氧化物歧化酶(SOD)、丙二醛(MDA)含量,Westernblot检测肾组织中p-P38蛋白表达情况。结果灌胃结束后,柚皮素低剂量组和柚皮素高剂量组血糖、尿素氮、肌酐水平,细胞凋亡率,肾脏组织中IL-1β、TNF-αmRNA表达量,Bax、Caspase-3、p-P38蛋白表达量均明显低于模型组(P均<0.05),且柚皮素高剂量组均明显低于柚皮素低剂量组(P均<0.05)。柚皮素低剂量组和柚皮素高剂量组肾脏组织中SOD表达量明显高于模型组(P均<0.05),MDA表达量明显低于模型组(P均<0.05),且柚皮素高剂量组SOD表达量明显高于柚皮素低剂量组而MDA表达量明显低于柚皮素低剂量组(P均<0.05)。结论柚皮素可通过p38MAPK信号传导通路抑制炎症细胞因子表达,减轻氧化应激反应,影响Bax和Caspase-3蛋白表达,从而延缓糖尿病肾病大鼠肾脏损伤,具有明显肾保护作用。Objective It is to study the protective effect of naringenin on renal injury in rats with diabetic nephropathy and its related mechanisms. Methods Twenty SPF SD rats were divided into blank group, model group, naringenin low dose group and naringenin high dose group according to the random principle, with 5 rats in each group. The rats in every group except blank group were given a high-fat diet and 1% streptozotocin 60 mg/kg by intraperitoneal injection to prepare diabetic nephropathy models. After confirming the successful modeling of diabetic nephropathy, the low-dose naringenin group and the high-dose naringenin group were respectively given naringenin 50 mg/kg and 100 mg/kg daily by gavage, and the blank group and the model group were given the same amount of normal saline every day, all one time/d, lasted for 4 weeks. After the end of the gavage, serum samples were taken to determine the levels of blood glucose, urea nitrogen and creatinine. Renal tissues were taken to detect the apoptosis of renal cells by flow cytometry, and to detect the expression of Bax and Caspase-3 protein in renal tissue by immunohistochemistry, real-time quantitative PCR was used to detect the expression of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) mRNA in renal tissue, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue were detected by spectrophotometer, the expression of p-P38 protein in renal tissue was detected by Western blot. Results After the end of gastric administration, the levels of blood glucose, urea nitrogen, creatinine, apoptosis rate, expression of IL-1β and TNF-α mRNA, Bax, Caspase-3 and p-P38 protein in kidney tissue in the low dose group and high dose group were significantly lower than that of the model group ( P <0.05), and these indexes in the high dose group was significantly lower than the low dose group ( P <0.05). The expression of SOD in the low-dose group of naringenin and the high-dose naringenin group was significantly higher and the expression

关 键 词：柚皮素 糖尿病肾病 凋亡 炎症反应 氧化应激反应 

分 类 号：R-332[医药卫生]