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目的探讨化瘀通络中药治疗糖尿病肾病蛋白尿可能的作用靶点。方法 60只SD大鼠随机选10只做为正常组,其余大鼠采用高糖高脂饲料喂养联合腹腔注射链脲佐菌素建立糖尿病肾病模型。将成模大鼠随机分为模型组15只、厄贝沙坦组14只、中药组15只。厄贝沙坦组给予厄贝沙坦片13.5 mg/(kg·d),中药组给予化瘀通络中药颗粒剂4.41 g/(kg·d),正常组及模型组给予等量饮用水灌胃,每日1次,共16周。分别于造模前(0周)及造模后第2、4、8、12、16周行24 h尿蛋白定量检测;第16周末取肾组织行光镜病理学观察,测量肾小球基底膜厚度并计数阴离子位点,检测肾组织硫酸乙酰肝素蛋白多糖(HSPG)、乙酰肝素酶(HPA)、足盂蛋白(PCX)的表达及尿PCX含量。结果模型组第2、4、8、12、16周24 h尿蛋白定量水平较同时间点正常组升高,厄沙贝坦组和中药组在第2、4、8、12、16周24 h尿蛋白定量水平低于同时间点模型组,并且中药组在12、16周24 h尿蛋白定量水平低于同时间点厄贝沙坦组(P<0.05或P<0.01)。厄贝沙坦组、中药组较模型组基底膜增厚减轻、阴离子位点数量增多(P<0.05),病理损伤得以改善。各组大鼠肾组织HSPG蛋白及mRNA表达差异无统计学意义(P>0.05);与模型组比较,厄贝沙坦组、中药组HPA蛋白及mRNA表达减少,PCX蛋白及mRNA表达增加,尿PCX含量下降(P<0.05)。结论化瘀通络中药可减少糖尿病肾病尿蛋白,其机制可能是抑制肾组织HPA的过表达,从而减少基底膜阴离子位点丢失,并能上调肾组织PCX的表达,减少尿PCX排泄,维持肾小球电荷屏障的完整性。
Objective To investigate the possible targets of Huayu Tongluo Chinese medicine in treating proteinuria of diabetic nephropathy. Methods Sixty SD rats were randomly selected as the normal group. The rest rats were fed with high glucose and high fat diet and streptozotocin intraperitoneally to establish diabetic nephropathy model. The rats were randomly divided into model group 15, irbesartan 14, traditional Chinese medicine group 15. The irbesartan group received 13.5 mg / (kg · d) of irbesartan and the traditional Chinese medicine group received 4.41 g / (kg · d) of traditional Chinese medicine granules of Huayu Tongluo. The normal group and the model group received the same amount of drinking water irrigation Stomach, once daily, for a total of 16 weeks. Urinary protein was detected 24 hours before modeling (0 week) and 2, 4, 8, 12 and 16 weeks after model making respectively. At the end of 16th week, the pathological changes of renal tissue were observed by light microscope and the glomerular basement The thickness of the membrane was counted and the anion sites were counted. The expression of HSPG, HPA and PCX in renal tissue and urinary PCX content were detected. Results The urinary protein levels at 24 h, 24, 8, 12 and 16 weeks in model group were significantly higher than those in normal group at 2, 4, 8, 12 and 16 weeks h urinary protein was lower than the model group at the same time points, and the urinary protein level of Chinese medicine group at 24th and 24th hour was lower than that of irbesartan group at 12 and 16 weeks (P <0.05 or P <0.01). The irbesartan group and the Chinese medicine group alleviated the thickening of the basement membrane, the number of anionic sites increased (P <0.05), and the pathological injury was improved. Compared with the model group, the expressions of HPA protein and mRNA in irbesartan group and traditional Chinese medicine group were decreased, the expression of PCX protein and mRNA was increased, and the expression of HSPG protein and mRNA in renal tissue of rats in each group was no significant difference (P> 0.05) PCX content decreased (P <0.05). Conclusion Huayu Tongluo herbs can reduce urinary protein in diabetic nephropathy by inhibiting the overexpression of HPA in renal tissue, decreasing the loss of anion sites in the basilar membrane, increasing the expression of PCX in renal tissue, decreasing urinary PCX excretion, maintaining renal The integrity of the ball charge barrier.