姜黄素衍生物B06对2型糖尿病大鼠肾脏的保护作用  

Protective effect of curcumin derivative B06 on kidney of type 2 diabetic rats

作　　者：曾聪聪[1] 刘曦[1] 刘网网 王玲[2] 程锦国[1] 陈三妹[3] 陈国荣[2] 

机构地区：[1]温州医科大学附属第二医院,浙江温州325000 [2]温州医科大学附属第一医院病理科,浙江温州325015 [3]绍兴文理学院医学院,浙江绍兴312000

出　　处：《中国应用生理学杂志》2015年第1期38-42,I0004,共6页Chinese Journal of Applied Physiology

基　　金：浙江省公益性技术应用研究计划项目(2011c23123);温州市高层次人才创新技术项目

摘　　要：目的:观察姜黄素衍生物B06对2型糖尿病大鼠肾脏的保护作用及机制。方法:雄性SD大鼠35只,随机均分成5组(n=7):正常对照组、高脂组、高脂治疗组、糖尿病组、糖尿病治疗组。采用高脂饮食结合链脲佐菌素诱导2型糖尿病大鼠模型。治疗组给予0.2 mg/kg·d剂量的B06灌胃,维持8周。检测血肌酐、尿素氮、尿酸,光镜和电镜观察大鼠肾组织的形态学改变,Masson染色观察肾组织的胶原纤维,并用免疫组化方法检测肾脏IV型胶原、纤维连接蛋白的表达。结果:糖尿病组大鼠血肌酐、尿素氮水平升高;光镜下见肾小球系膜基质增多,胶原纤维增多,肾小球毛细血管基底膜增厚;电镜下足细胞足突肿胀及足突融合;Masson染色示肾小球亮绿色阳性基质增多;免疫组化显示IV型胶原、纤维连接蛋白的表达水平升高。经B06干预后,血肌酐、尿素氮下降;肾小球病变减轻,肾脏组织IV型胶原、纤维连接蛋白的表达水平降低。结论:B06对2型糖尿病大鼠的肾脏具有保护作用,其机制可能是通过降低肾脏IV型胶原、纤维连接蛋白的表达,从而抑制细胞外基质的积聚和肾小球系膜增殖,发挥抗肾纤维化的作用。Objective： To observe the effect and mechanism of curcumin derivative B06 on kidney from rats with hyperlipidemia and type 2 diabetes. Methods： Thirty five male SD rats were randomly divided into five groups（ n = 7） ： the normal control group,high-fat group,high-fat ＋ B06-treatd group,diabetic group,diabetic ＋ B06-treated group. After fed with high-fat diet for 4 weeks,the later two groups were injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. B06-treated groups were given B06 by gavage at a dosage of 0. 2 mg / kg·d for 8 weeks. After the treatment,the serum creatinine,blood urea nitrogen and uric acid were detected biochemically,the morphology of kidney was observed with light and transmission electron microscopy,the expression of collagen fibers was observed with Masson staining,the protein expression of collogen IV and fibronectin in kidney were determined by Immunohistochemistry. Results： It was showed that the levels of the serum creatinine and blood urea nitrogen elevated significantly in diabetic group. In high-fat and diabetic groups,increased glomerular mesangial matrix and collagen fiber and thicken glomerular basal membrane were observed under light microscopy,swelling and fusion of foot process were found under electron microscope; increased green matrix within glomeruli was observed under Masson staining. collogen IV and fibronectin protein expression were significantly enhanced in high-fat group and diabetic group. After B06＇s intervention,the levels of serum creatinine and blood urea nitrogen were decreased in diabetic groups,the morphological change of kidney was obviously relieved,Collogen IV and fibronectin protein expression reduced. Conclusion： Curcumin derivative B06 exerts a protective effect on kidney in type 2 diabetic rats,reduced expressions of collogen IV and fibronectin,inhibition of the accumulation of extracellular matrix and glomerular mesangial proliferation,and then prevention of renal fibrosis may be the mechanism.

关 键 词：糖尿病 高脂 姜黄素衍生物B06 IV型胶原 纤维连接蛋白 肾脏 大鼠 

分 类 号：R587.1[医药卫生—内分泌]