重组球形脂联素减轻糖尿病小鼠肾脏损伤

目的探讨重组球形脂联素(APN)是否通过调节自噬和内质网应激减轻糖尿病小鼠肾脏损伤。方法将小鼠随机分为对照组、糖尿病模型组、脂联素低和高剂量组(腹腔注射5和15μg/kg重组球形脂联素),每组8只。8周后取血用生化方法测定血糖、尿素氮和肌酐,用酶联免疫法测定胰岛素;取双侧肾脏计算肾脏质量/体质量;取部分肾脏皮质行HE染色,余保存于-70℃冰箱待用;用实时定量PCR测定内质网应激指标(GRP78、CHOP和caspase-12)和自噬指标(LC3、Beclin1和p62)mRNA表达。结果与对照组比较,模型组小鼠血糖、肌酐、尿素氮、肾质量/体质量水平均显著升高(P<0.05);胰岛素水平显著降低(P<0.05);肾脏病理改变加重;肾脏GRP78、CHOP、caspase-12和p62 mRNA表达显著升高(P<0.05);LC3和Beclin1 mRNA表达显著降低(P<0.05)。与模型组比较,脂联素可显著缓解模型组的上述变化(P<0.05)。结论重组球形脂联素通过调节自噬和内质网应激减轻糖尿病小鼠肾脏损伤。

Recombinant globular adiponectin relieves kidney injury in diabetic mice

Objective To investigate whether recombinant globular adiponectin can reduce kidney injury in diabetic mice by regulating autophagy and endoplasmic reticulum stress.Methods Mice were randomly divided into control group,diabetic model group,low and high dose of adiponectin group(5 and 15μg/kg dose of recombinant globular adiponectin was injected).There were 8 mice in each group.After eight weeks,blood samples were collected to determine the level of blood glucose,urea nitrogen and creatinine by biochemical method and the level of insulin was measured by enzyme-linked immunosorbent assay.Bilateral kidneys were taken to calculate the ratio of the kidney mass to body mass.The renal cortex tissue samples were stained with HE,and the rest were kept at-70℃.The mRNA expression of endoplasmic reticulum stress indicators(GRP78,CHOP and caspase-12)and autophagy indicators(LC3,Beclin1 and p62)was determined by real-time quantitative PCR.Results Compared with control group,the level of blood glucose,creatinine and urea nitrogen,and the ratio of the kidney/body mass were significantly increased(P<0.05),and the level of blood insulin was significantly reduced(P<0.05)in model group.There were significant pathological changes in kidney in diabetic mice in model group compared with control group.The mRNA expression of GRP78,CHOP,caspase-12 and p62 was significantly increased(P<0.05),and themRNA expression of LC3 and Beclin1 was significantly reduced(P<0.05)in kidney in model group compared with control group.Compared with model group,adiponectin can significantly relieve the changes in model group(P<0.05).Conclusions Recombinant globular adiponectin may alleviate the renal injury in diabetic mice by regulating autophagy and endoplasmic reticulum stress.