真武汤加味对糖尿病肾病大鼠肾功能及其肾组织中IGF-1表达的影响

Effects of Modified Zhenwu Decoction (真武汤) on Kidney Function and IGF-1 Expression in Renal Tissue of Diabetic Nephropathy Model Rats

目的探讨真武汤加味治疗糖尿病肾病的可能作用机制。方法 40只雄性SD大鼠随机等分为正常组、模型组、真武汤低剂量组及真武汤高剂量组。除正常组外,其余各组采用高脂饲料喂养联合腹腔注射链脲佐菌素建立大鼠糖尿病肾病模型。造模成功后真武汤低、高剂量组分别给予真武汤2.45、9.80 g/(kg·d)灌胃,正常组及模型组给予等体积蒸馏水灌胃,均每日1次。给药16周后观察肾组织病理变化,测定各组大鼠血尿素氮(BUN)、血肌酐(Scr)、尿肌酐(Ucr)水平及24 h尿蛋白定量,并测定肾小球系膜阳性目标积分光密度(IOD)及肾组织中胰岛素样生长因子1(IGF-1)蛋白、mRNA表达。结果与正常组比较,模型组24 h尿蛋白定量及BUN、Scr均显著升高,Ucr显著降低,IOD值显著升高,肾组织基底膜明显增厚,系膜细胞明显增生及结节状硬化形成,肾组织中IGF-1蛋白及mRNA表达量明显升高(P<0.05);与模型组比较,真武汤低、高剂量组24 h尿蛋白定量、BUN、Scr均显著降低,Ucr显著升高,IOD值显著降低,肾脏组织病理改变明显减轻,肾组织中IGF-1蛋白及mRNA表达量明显降低(P<0.05);而真武汤高剂量组变化较真武汤低剂量组更显著。结论真武汤加味能减少糖尿病肾病大鼠24 h尿蛋白定量、降低Scr及BUN水平,升高Ucr水平,减轻肾组织病理学改变,其机制可能与其调节IGF-1表达有关。

Objective To observe the possible mechanism of Modified Zhenwu Decoction（ 真武汤） in treating diabetic nephropathy（ DN）. Methods A total of 40 male SD rats were selected and randomly and equally divided into normal control group（ NC group）,model control group（ DN group）,low dose of Zhenwu Decoction（ 真武汤）group（ EL group）,high dose of Zhenwu Decoction group（ EH group）. The rat models of DN were established by the single injection of streptozotocin（ STZ）. The rats in EL group and EH group were respectively administered with Zhenwu Decoction 2. 45 g/（ kg· d） and 9. 8 g/（ kg · d）,while NC group and DN group were administered with equal volume distilled water once a day. After 16 weeks＇ administration,the blood urea nitrogen（ BUN）,serum creatinine（ Scr）,urine creatinine（ Ucr） levels and 24 h urine protein quantitation in rats of each group were determined,and mesangial positive target integrated optical density（ IOD）,the expressions of insulin-like growth factor 1（ IGF-1） protein and mRNA in renal tissue were detected. Results Compared with NC group,the 24 hours urinary protein quantitative,levels of BUN and serum Scr in DN group were significantly increased,and the level of Ucr was significantly decreased,and the IOD was significantly increased. The kidney basement membrane was thickened obviously,mesangial cells were obviously proliferated and nodular sclerosis was formed. The IGF-1 protein and mRNA expressions were increased significantly in DN group（ P〈0. 05）. Compared with the DN group,the levels of 24 hours urinary protein quantitative,BUN and Scr in EL and EH groups were significantly decreased,and the level of Ucr was significantly increased. The IOD was significantly decreased,and the pathological damage of kidney tissue was significantly alleviated. The IGF-1 protein and mRNA expressions were decreased significantly（ P〈0. 05）. The changes of EH group were more obviously than EL group. Conclusion Modified Zhenwu Decoction can reduce the levels of24-hour urine protein,BUN and Scr,increase the levels of Ucr,and alleviate the pathological damage of kidney tissue in diabetic nephropathy rats. The molecular mechanism may be related to the regulation of Zhenwu Decoction on IGF-1 expression.