清道夫受体A在实验性小鼠糖尿病发病中的作用研究

Scavenger receptor A type Ⅰ/Ⅱ is involved in the development of diabetic models in mice induced by streptozotocin

目的:研究清道夫受体A(SR-A)在小鼠糖尿病发病中的作用。方法:取雄性野生型(SR-A(+/+))小鼠和清道夫受体A敲除(SR-A(-/-))小鼠各60只,分别随机分成两组。采用链脲左菌素(STZ)50mg/(kg·d)连续5d腹腔注射诱导糖尿病模型,以血糖超过16.7mmol/L为糖尿病模型,分别于造模后0w,4w,8w测血糖、体重和24h尿白蛋白排泄率;于注射STZ后0,10d,4w,8w杀检。并留取胰腺和肾组织,测肾重、计算肾重/体重比值,并测定肾小球体积。结果:注射STZ的小鼠均有不同程度的多饮、多食、多尿和体重下降等糖尿病症状。SR-A(+/+)小鼠血糖水平、肾重、肾重/体重比值、肾小球体积、24h尿白蛋白排泄率和死亡率较SR-A(-/-)小鼠明显增高。SR-A(+/+)小鼠的胰岛、血管周围、导管周围、小叶间隔及胰岛周围区域有大量单个核细胞和CD68阳性细胞的浸润,而SR-A(-/-)小鼠的胰腺组织几乎无炎性细胞浸润。结论:SR-A在STZ诱导的实验性小鼠糖尿病模型的发生发展中可能起重要作用,可能通过促进巨噬细胞和单个核细胞在胰岛的局部浸润而诱导胰岛B细胞的损伤。

Objective:To investigate whether scavenger receptor class A type Ⅰ/Ⅱ is involved in the development of diabetic models in mice.Methods:Male C57BL/6 homozygous SR-A knock out(SR-A(-/-))mice and control(SR-A(+/+))mice received 5 consecutive daily intraperitoneal injections of streptozotocin(50mg per kilogram of body weight) to induce diabetes.Diabetes was confirmed by serum glucose levels exceeding 16.7mmol/L during the experimental period of 8 weeks.The pancreas tissue were obtained from diabetic and control mice at 0,10d,4w and 8w after STZ injected respectively.The serum insulin,serum glucose,advanced glycosylation end products,urinary albumin excretion and kidney weight/body weight ratio were measured.The kidney tissue was used for evaluating the kidney weight/body weight ratio and morphometric studying of glomerular size.Results:SR-A(-/-) mice were highly resistant to diabetes development compared with control mice and had higher serum insulin levels during the experimental period of 8 weeks.The serum levels of glucose,AGEs and 24h urinary albumin excretion,weight/body weight,ratio,pancreatic islets,perivascular,periductular,peri-islet areas and interlobular septa in control mice increased significantly compared with SR-A(-/-) mice.The in control mice were heavily infiltrated by mononuclear cells and CD68-positive cells compare with SR-A(-/-) mice.Conclusions:The in vivo evidence in this study suggest SR-A may be involved in the development of diabetic models by the ways of mediating the infiltration of macrophage and mononuclear cells in the pancreas in mice.