镰形棘豆总黄酮对糖尿病KKay小鼠肾小管上皮细胞转分化的影响

Effect of Total Flavone of Lianxingjidou(Oxytropis falcate Bunge) on Transdifferentiation of Renal Tubular Epithelial Cells in Diabetic KKay Mice

目的观察镰形棘豆总黄酮对糖尿病KKay小鼠肾小管上皮细胞转分化的影响。方法选择糖尿病KKay小鼠模型,分别以低、中、高剂量(0.1、0.2、0.4 g/kg)的镰形棘豆总黄酮每日灌胃1次,连续4周。每天给药前观察动物一般状况;造模的第0、2、4周分别检测记录一般状况、体质量和空腹血糖;第5周时,取肾脏组织进行HE染色,采集的血清中肌酐(creatinine,Cr)、尿素氮(urea nitrogen,BUN)、尿酸(uric acid,UA)含量变化用于评价肾功能以及检测肾间质中的基因、蛋白表达。结果与模型组比较,镰形棘豆总黄酮可以剂量相关性地减轻糖尿病KKay小鼠的体质量、血糖显著下降(P<0.05);24 h尿微量白蛋白(UAlb)显著下降,血清中Cr、BUN以及UA均显著降低(P<0.05);肾脏组织形态学观察肾组织中肾小球数量明显增多,肾小球细胞数目以及肾小球系膜区细胞外基质(extracelluar matrix,ECM)明显减少;抗体E-钙黏连蛋白(E-cadherin)的表达水平有所提高,而α-平滑肌肌动蛋白(α-SMA)的表达显著下降(P<0.05);肾间质中的Ⅰ型胶原、Ⅲ型胶原、血清纤维连接蛋白(FN)表达下降(P<0.05)。结论镰形棘豆总黄酮能够提升体质量,降低血糖,显著降低Cr、BUN以及UA,抑制肾组织中肾小球凋亡,降低肾小球细胞数目以及ECM,一定程度上提高E-cadherin的表达水平,抑制α-SMA的表达,提示镰形棘豆总黄酮具有抑制肾小管上皮细胞转分化的作用。

Objective To observe the effect of total flavone of Lianxingjidou(Oxytropis falcate Bunge)on transdifferentiation of renal tubular epithelial cells in diabetic KKay mice.Methods Diabetic KKay mice were selected,respectively,in low,medium,low and high doses(0.1,0.2,0.4 g/kg)of total flavone of Lianxingjidou(Oxytropis falcate Bunge)were administered by gavage once a day for 4 weeks.The general condition of the animals was observed before administration every day.The general condition,body mass and fasting blood glucose were detected and recorded at the 0,2 and 4 weeks of modeling.At the 5 th week,the renal tissue was stained with HE,and the contents of creatinine(CR),urea nitrogen(BUN)and uric acid(UA)in the collected serum were measured to evaluate renal function and detect gene and protein expression in renal stroma.Results Compared with the model group,the total flavone of Lianxingjidou(Oxytropis falcate Bunge)can reduce the body mass of diabetic KKay mice in a dose-dependent manner.Blood glucose was decreased significantly(P<0.05).The 24-hour UAlb was decreased significantly,and serum levels of Cr,BUN and UA were decreased significantly(P<0.05).The renal histomorphology showed that the number of glomeruli in renal tissue was increased significantly,and the number of glomerular cells and ECM was decreased significantly.The expression level of E-cadherin was increased,but the expression ofα-SMA was decreased significantly(P<0.05),and the expressions of type I collagen,type III collagen and FN in renal stroma were decreased(P<0.05).Conclusion The total flavone of Lianxingjidou(Oxytropis falcate Bunge)could increase body weight,decrease Cr and BUN and inhibit glomerular apoptosis,decrease the number of glomerular cells and increase the expression level of E-cadherin to some extent.