波动性高血糖对糖尿病大鼠肾脏HO-1γ-GCS及Nrf2表达影响

摘要

Objective To observe the expression of HO-1,γ-GCS and Nrf2 in high blood-glucose fluctuation of diabetic rats kidney. Methods Twenty-four male Sprague-Dawley(SD)rats were randomly divided into normal group(group N,n=8)and diabetic model group (n=16).The diabetic rat model was established by injection of a small dose of streptozotoein(STZ)after feeding them with high-fat diet for 2 weeks,and then they were randomly divided into the sustained high glucose diabetic rat model group(group S,n=8)and the high blood-glucose fluctuation rat model group(group F,n=8).The model of high blood-glucose fluctuation rat were developed by alternative intraperitoneal injection of insulin and glucose. Successfully-established model rats were randomly divided into four groups:low(14mg/(kg·d),group FL),middle (28mg/(kg·d),group FM),high(56mg/(kg·d),group FH)dosage of ginseng treatment group and control group(group FO).After 8 weeks levels of SOD,MDA and ROS were measured and expression of HO-1,γ-GCS and Nrf2 were observed.Results Compared with group N, levels ofMDA,ROS in S and F groups were significantly increased(P<0.05),compared with group S,levels of MDA and ROS in group F were significantly increased(P<0.05).Compared with group N,levels of SOD in S and F groups were significantly decreased(P<0.05),compared with group S,levels of SOD in group F were significantly decreased(P<0.05).Compared with group N,expressions of HO-1,γ-GCS and Nrf2 in S and F groups were significantly increased(P<0.05),compared with group S,expressions expression of HO-1,γ-GCS and Nrf2 in group F were significantly increased(P<0.05).Conclusion High blood-glucose fluctuation causes a more significant damage for oxidative stress to kidney.%目的 观察糖尿病大鼠波动性高血糖状态下肾脏组织HO-1、γ-GCS及Nrf2的表达.方法将24只雄性SD大鼠随机分成正常对照组(N组,n=8)和糖尿病模型组(n=16),高脂饲料喂养加小剂量链脲佐菌素(STZ)诱导建立糖尿病大鼠模型,随机分为稳定高糖组(S组,n=8)和波动性高糖组(F组,n=8),喂养8周.实验结束后主动脉取血,检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧簇(ROS)水平,取肾脏组织,HE染色观察肾脏组织病理变化,免疫组化测定HO-1、γ-GCS及Nrf2的表达.结果与N组比较,S组及F组血清SOD浓度明显减少,MDA、ROS浓度均明显增加(P<0.05);与S组比较,F组MDA、ROS浓度明显增加,SOD浓度明显减少(P<0.05).与N组比较,S组及F组HO-1、γ-GCS及Nrf2表达均增多(P<0.05);与S组比较,F组HO-1、γ-GCS及Nrf2表达增多(P<0.05).结论波动性高血糖引发的肾脏氧化应激水平增高,Nrf2和其转录调控的下游抗氧化蛋白HO-1和γ-GCS参与了糖尿病肾病的抗氧化防御机制.