抑瘤素及其受体在高脂饮食大鼠肾组织中的表达和意义

Expression and significance of OSM and OSMR in kidney of high-fat diet rat

目的:探讨抑瘤素M(OSM)及其受体(OSMR)在高脂饮食大鼠肾组织中的表达和意义。方法:随机将30只SD大鼠分为对照组(n=15)和高脂组(n=15)。对照组以普通饲料喂养,高脂组以高脂饲料喂养,12周时检测大鼠24h尿蛋白定量、尿肌酐,计算内生肌酐清除率(Ccr),检测血清总胆固醇(CH)、三酰甘油(TG)、空腹血糖(FPG)。放射免疫法测空腹胰岛素水平(FINS),ELISA法测血清OSM水平;光镜观察肾组织病理改变,免疫组化法观察肾组织OSM、OSMR的表达,Western Blot检测肾组织OSM及OSMR蛋白表达。结果:12周时,与对照组相比高脂组大鼠血脂水平、血糖、胰岛素抵抗指数(IRI)、24h尿蛋白定量、血清OSM浓度明显升高(P<0.05),Ccr无明显变化(P>0.05)。光镜下高脂组肾小球系膜细胞及基质稍增多,肾小管上皮细胞淡染、浊肿、体积增大、胞质增多,未见明显的空泡颗粒。免疫组化及Western Blot均显示高脂组较对照组肾组织OSM及OSMR表达明显增多,高脂组血清OSM浓度和24h尿蛋白定量、CH、TG及IRI呈高度正相关(P<0.01),与FPG有相关性(P<0.05)。结论:炎症因子OSM及OSMR在高脂饮食大鼠肾脏表达明显增多,可能通过促进炎症反应、介导胰岛素抵抗形成参与脂质肾损害的病理过程。

Objective：To investigate the expression and significance of OSM and OSMR in kidney of high-fat diet rat. Methodology：Sprague Dawley rats were randomly divided into two groups：control diet group （n = 15） and high-fat diet group （n= 15）. At the 12th week, the levels of serum cholesterol （CH）, triglyceride （TG）, fasting blood glucose （FBG） and fasting insulin （FINS）, 24 hour urine protein excretion and creatinine clearance rate （Ccr） were measured. The level of serum OSM were detected by ELISA. The histopathologic changes were observed under optic microscope. The expression of OSM and OSMR in renal tissue were detected by immunohistochemitry, and the protein expression of OSM and OSMR by Western Blot. Results：Compared with control group, the levels of serum CH, TG, FPG, OSM and 24 hour urine protein excretion were significantly increased in high-fat group （P〈0.05） ,but the Ccr has no statistical differences between the two groups（P〉0. 05）. Compared with control group, the expression of OSM and OSMR was significantly increased on the cytoplasm and ceU membrane of renal tubular epithelial cells in high-fat diet group. The expression of OSM and OSMR proteins was also significantly increased in high-fat diet group. The expression of OSM was positive correlation with the levels of serum FPG, IRI, CH, TG and 24 hour urine protein. Conclusion： The expression of OSM and OSMR were significantly increased on the kidney of high-fat diet rats, which may be involve in the renal injury through insulin resistance and promote inflammatory reaction.