摘要
目的 探讨活性维生素D对糖尿病肾病大鼠足细胞损伤的抑制作用及其可能机制.方法 将SD雄性大鼠随机分为四组：对照组（NC组）、活性维生素D组（VD组,骨化三醇0.1 μg· kg-1·d-1灌胃）、糖尿病肾病组（DN组,腹腔注射STZ 58 mg/kg）、糖尿病肾病＋活性维生素D组（DN＋VD组）.定期检测血糖、体质量,收集尿标本,18周末处死动物,检测Scr、BUN和尿蛋白变化.PAS及MASSON染色观察肾脏病理改变.电镜观察足细胞超微结构变化.免疫组化法检测肾组织Nephrin、Podocin、Desmin及VDR的表达.Western印迹检测Podocin、Nephrin、Desmin、VDR、PI3K-p85、Akt及p-Akt表达.结果 与DN组比,DN＋VD组蛋白尿减低达36％,肾脏病理损伤减轻,足细胞损伤减轻,血糖、体质量以及血尿素氮无差异（均P＞ 0.05）.血肌酐、钙、磷在四组之间未见差异（均P＞ 0.05）.与NC组比较,DN组Podocin、Nephrin,VDR,PI3K-p85和p-Akt表达量均明显减低（均P＜0.05）,足细胞损伤标志Desmin蛋白表达量显著增加（均P＜ 0.05）.与DN组比,DN＋VD组Podocin、Nephrin,VDR,PI3K-p85和p-Akt表达量明显增加（均P＜ 0.05）,Desmin蛋白表达量明显减低（P＜0.05）.相关性分析显示,Nephrin与VDR呈正相关（r=0.776,P＜0.05）,与PI3K-p85及p-Akt也呈明显的正相关（r=0.736,r=0.855,均P＜0.05）.结论 活性维生素D能够显著抑制STZ诱导的糖尿病肾病大鼠足细胞损伤,其分子机制可能与PI3K/p-Akt信号通路有关.
Objective To investigate the effects and underlying mechanism of calcitriol on ameliorating podocytes impairment in DN rats.Methods SD rats were randomly divided into four groups：normal control （NC） group,calcitriol treatment （VD） group：calcitriol 0.1μg· kg--1 d-1,diabetic nephropathy （DN） group：streptozocin （STZ） 58 mg/kg,DN treated with calcitriol （DN ＋ VD） group：calcitriol 0.1 μg · kg-1 · d-1 ＋ STZ 58 mg/kg.Rats were sacrificed at the end of 18 weeks.Results Compared with the DN group,the DN ＋ VD group exhibited significantly lower proteinuria by 36％,improved renal histology at the end of the experiment （P ＜ 0.05）,and similar levels of blood glucose,serum urea nitrogen as well as body weight （P ＞ 0.05）.There were no significant differences in the serum concentrations of creatinine,calcium and phosphorus among the four groups （P ＞ 0.05）.In DN group,the expressions of nephrin,podocin,VDR,PI3K-p85 and p-Akt were significantly decreased and the expression of desmin was increased compared to NC group.Calcitriol treatment could attenuate the above changes.Additionally,a positive correlation was observed between the expressions of nephrin and VDR （r=0.776,P ＜ 0.05）.Likewise,the expression of nephrin was positively correlated with either PI3K -p85 or p-Akt （r=-0.736,r=0.855,all P ＜ 0.05）.Conclusion Calcitriol can ameliorate podocytes injury in DN rats,which might be related with the further up-regulation of PI3K/p-Akt signaling pathway.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2014年第10期777-783,共7页
Chinese Journal of Nephrology
基金
国家自然科学基金项目（No.81370826）
江苏省十二五医学重点人才项目（RC2011124）
中央高校基本科研业务费专项资金资助项目（CXLX13-122）
