摘要
目的:探讨骨化三醇对糖尿病肾病模型大鼠肾小管间质损伤的保护作用及其可能的机制。方法:取SD大鼠随机分为正常对照组、模型组(橄榄油)、干预组(骨化三醇0.03μg·kg-1·d-1),每组8只,后2组单次腹腔注射链脲佐菌素建立糖尿病肾病模型,建模成功后灌胃给予相应药物,连续12周,末次给药后检测24h尿蛋白,然后处死大鼠,检测血清尿素氮(BUN)、血肌酐(Scr)含量及肾组织中肌成纤维细胞特异性蛋白α-平滑肌肌动蛋白(α-SMA)和细胞外基质(ECM)重要成分纤维连接蛋白(FN)及其mRNA的表达情况,并对肾小管和小管间质损伤进行评分。结果:与正常对照组比较,模型组和干预组24h尿蛋白、BUN、Scr及α-SMA和FN蛋白、mRNA表达均明显增加(P<0.05);与模型组比较,干预组24h尿蛋白、Scr及α-SMA和FN蛋白、mRNA表达均明显减少(P<0.05),肾小管和小管间质损伤评分明显降低(P<0.05)。结论:活性维生素D3可能通过下调糖尿病肾病模型大鼠肾组织中α-SMA、FN的表达,抑制肾小管上皮细胞转分化,减轻肾小管间质的ECM沉积,进而发挥其肾脏保护作用。
OBJECTIVE：To investigate the protective effects and mechanism of rocalirol on renal tubulointerstitium damage in rats with diabetic nephropathy.METHODS：SD rats were randomly divided into normal control group,model group（florence oil）,intervention group（rocalirol 0.03 μg·kg-1·d-1） with 8 rats in each group.The latter 2 groups were given intraperitoneal injection of streptozotocin to establish diabetic nephropathy model.After modeling,they were given relevant medicine intragastrically for consecutive 12 weeks.24 hours urinary protein was determined after the last administration and then rats were sacrificed.The contents of blood urea nitrogen（BUN） and serum creatinine（Scr） were measured,and the expression of α-smooth muscle actin（α-SMA） and fibronectin（FN） protein in ECM were determined as well as the expression of FN mRNA and α-SMA mRNA in the kidney.The kidney tubules injury and tubulointerstitial injury were scored.RESULTS：Compared with normal control group,24 h urinary protein,BUN and Scr,the protein and mRNA expression of α-SMA and FN all increased significantly in model group and intervention group（P0.05）.Compared with model group,24 h urinary protein,Scr,the protein and mRNA expression of α-SMA and FN decreased significantly in intervention group（P0.05）;kidney tubules injury and tubulointerstitial injury scores were decreased significantly（P0.05）.CONCLUSION：Rocalirol has protective effects on kidney tissue,of which the mechanism maybe related to that rocalirol can depress the expression of α-SMA and FN in the kidney of rats with diabetic nephropathy,inhibit the differentiation of renal tubular epithelial cells and relieve the ECM precipitation of renal tubulointerstitium.
出处
《中国药房》
CAS
CSCD
2012年第9期806-808,共3页
China Pharmacy
