摘要
目的通过观察血管生成素样蛋白2(ANGPTL2)在2型糖尿病大鼠肾脏中的表达,探讨其对足细胞损伤的影响及雷公藤甲素的干预机制。方法 50只SD雄性大鼠随机分为正常对照组(NC,10只)和实验组(40只),实验组予高糖高脂喂养联合小剂量链脲佐菌素(STZ 30 mg/kg)建立2型糖尿病大鼠模型,成功建立模型(32只)再随机分为2组:糖尿病对照组(DM,16只)及雷公藤甲素组(DT,16只)。雷公藤甲素干预8周后,测体重、血压、肾重、血糖、血肌酐(Scr)、尿素氮(BUN),24 h尿蛋白(UAL)的排泄量;镜下观察肾组织病理改变;免疫组化染色技术、实时定量PCR及Western blot法检测肾组织ANGPTL2、Nephrin及Podocin mRNA及蛋白表达的变化。结果 DM组24 h UAL排泄量明显高于NC组(9.07±0.13,0.73±0.03,P<0.01),同时ANGPTL2 mRNA及蛋白表达量明显升高(P均<0.01),Nephrin及Podocin的mRNA及蛋白表达量明显降低(P<0.01),DT组较DM组24 h UAL排泄量降低(5.51±0.07,9.07±0.13,P<0.01),足细胞损伤改善,ANGPTL2 mRNA及蛋白表达量降低(P<0.01),Nephrin及Podocin的mRNA及蛋白表达量升高(P<0.01),且ANGPTL2 mRNA及蛋白表达量与尿白蛋白呈正相关(r=0.768,r=0.989,P<0.01),其与Nephrin及Podocin的mRNA及蛋白表达量呈负相关(r=-0.711,r=-0.700;=-0.983,r=-0.945;P均<0.01)。结论 ANGPTL2可能通过下调Nephrin及Podocin表达参与足细胞损伤机制,雷公藤甲素可下调ANGPTL2在肾脏的表达,保护足细胞。
Objective To observe the effect of angiopoietin-like protein 2 （ANGPTL2） on the podocytes in the kidney of 2 type diabetes（T2DM） rat models and asscess the influence of triptolide on ANGPTL2, and discuss their mechanism. Methods 50 SD male rats were divided into normal control group （NC, n=10） and experimental group （n=40） randomly. The experimental group was fed with high sugar-fat diet and given a low dose streptozocin （STZ 30 mg/kg） established type 2 diabetic model rats, and then the successful induced models randomly divided into 2 groups：diabetes control group （DM） and triptolide group （DT）. Weight, blood pressure, blood glucose, serum creatinine （Scr）, blood urea nitrogen （BUN）, 24 hour urinary albumin （UAL） and renal histomorphology were observed after Drug intervention for 8 weeks, the expression of ANGPTL2, Nephrin and Podocin in renal tissue were detected by immunohistochemisty, real-time PCR and Western blot. Results UAL in DM group were obviously higher, compare to the NC group （9.07±0.13, 0.73±0.03, P＆lt;0.01）, and the mRNA and protein of ANGPTL2 distantly was upregulated compared with NC group （P＆lt;0.01）, the mRNA and protein of Nephrin and Podocin were significantly decreased（P＆lt;0.01）;Meanwhile UAL was significantly lower（5.51±0.07 9.07±0.13,P＆lt;0.01） compared with DM group, and the mRNA and protein of ANGPTL2 downregulated （P＆lt;0.01）. Neverthless, the mRNA and protein of Nephrin and Podocin were significantly upregulated. Conclusion these results indicate that the expression of ANGPTL2 in kidney tissue of T2DM rats could decrease the expression of Nephrin and Podocin to induce the injury of the podocytes and triptolide could decrease ANGPTL2.
出处
《中华临床医师杂志（电子版）》
CAS
2013年第23期190-193,共4页
Chinese Journal of Clinicians(Electronic Edition)
基金
青岛市科技局课题[2012-1-3-1-(19)-nsh]
