二至丸提取物对糖尿病肾病大鼠足细胞损伤的保护作用研究
Study on the Protective Effect of Erzhi Formula Extraction on Podocyte Injury in Diabetic Nephropathy Rats
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摘要: 目的 探讨二至丸提取物(EZF)保护足细胞而抑制糖尿病模型大鼠肾损伤的机制。方法 采用STZ及高糖高脂饲料联合复制大鼠糖尿病肾病模型,考察EZF对大鼠尿蛋白量、肾指数、肾脏中炎症因子和抗氧化指标、肾脏病理结构变化(HE/PAS染色)以及足细胞裂孔膜CD2AP和podocin蛋白表达量。结果 与模型组比较,EZF各剂量组的24 h尿蛋白量均显著降低(P<0.05);EZF能够显著抑制模型组大鼠的体质量降低(P<0.01),并能显著抑制肾指数的增加(P<0.05);EZF高、中剂量组均可显著降低大鼠肾脏中IL-β、TNF-α和IL-6的水平(P<0.05~0.01);EZF高、中剂量组均显著降低大鼠肾脏中MDA含量(P<0.05),且显著提高SOD活力(P<0.05);HE和PAS染色表明,EZF对模型组大鼠的病理变化有减轻作用,且肾小球形态基本恢复正常;Western blot法对DN大鼠肾脏中CD2AP和podocin的蛋白表达的检测结果表明,EZF各剂量组大鼠肾组织中podocin、CD2AP蛋白表达量均显著升高(P<0.05)。结论 EZF可调节足细胞裂孔膜蛋白CD2AP和podocin表达而保护足细胞,进而修复肾功能而抗糖尿病肾病。Abstract: OBJECTIVE To elucidate the protective effect of Erzhi formula (EZF) on the podocyte injury in diabetic nephropathy (DN) rats. METHODS STZ and high glucose and high-fat diet were used to replicate the diabetic nephropathy rat model. The changes of blood glucose, urine protein, renal index, renal pathological changes (HE/PAS staining), and CD2AP and podocin protein expression in the podocyte membranes were investigated. RESULTS After 8 weeks treatment of EZF extraction, each dose group showed hypoglycemic effect. Compared with the model group, EZF extraction significantly decreased the 24 h urinary protein (P<0.05); After 16 weeks intervention, the body weight in the model rats were significantly reduced (P<0.01), renal index were increased significantly (P<0.05); HE and PAS staining showed that the pathological changes of model rats were alleviated and the glomerular morphology were normal after the treatment of EZF extraction. The expression of CD2AP and Podocin protein in DN rat kidney were detected by Western blotting method. The results showed that compared with the model group, EZF significantly increased the expression podocin and CD2AP protein (P<0.05,P<0.01). CONCLUSION EZF can inhibit renal injury and repair renal function in diabetic rats, and this function may be mediated by the protection of the podocyte and the regulation of the expression of CD2AP and podocin in its pore membrane protein.
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Key words:
- Erzhi formula /
- diabetic nephropathy /
- podocyte /
- podocin /
- CD2AP protein
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[1] LOEFFLER I, WOLF G. Epithelialtomesenchymal transition in diabetic nephropathy: fact or fiction?[J]. Cells, 2015, 4(4): 631652.〖ZK)〗 [2] 洪金妮,黎巍威,王学美. 糖尿病肾病中足细胞损伤的信号通路及中药的干预研究进展[J]. 中药药理与临床,2017,33(3): 215218.〖ZK)〗 [3] 张莉,王瑜,杜桂英,等. Toll样受体4在糖尿病肾病患者肾组织中的表达及厄贝沙坦的干预作用[J]. 华中科技大学学报(医学版),2017,46(1): 4045.〖ZK)〗 [4] 李丽华, 赵祎镭, 焦红.厄贝沙坦相关左侧颈部、腋下淋巴结及左侧乳房疼痛[J] .药物不良反应杂志, 2010, 12(1): 44.〖ZK)〗 [5] 吴旻. 扶寿精方[M]. 北京: 中医古籍出版社,1986:11.〖ZK)〗 [6] 刘端勇,赵海梅. 从滋阴入手,以二至丸调治亚健康的理论解析[J]. 时珍国医国药,2012,23(1):217219.〖ZK)〗 [7] 李志杰,张悦,刘煜敏,等.黄芪多糖对早期糖尿病肾病大鼠足细胞nephrin和podocin表达的影响[J]. 中国病理生理杂志,2011,27(9): 17721776.〖ZK)〗 [8] 方敬,陈志强,郭倩,等. 化瘀通络中药对糖尿病肾病大鼠肾脏足细胞裂孔膜蛋白podocin、CD2AP的调节作用[J]. 中国中西医结合杂志,2016,36(7):835838.〖ZK)〗 [9] SHONO A, TSUKAGUCHI H, YAOITA E, et al. Podocin participates in the assembly of tight junctions between foot processes in nephrotic podocytes[J]. J Am Soc Nephrol, 2007, 18(9):25252533.〖ZK)〗 [10] SAURUS P, TOLVANEN TA, LINDFORS S, et al. Inhibition of SHIP2 in CD2APdeficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis[J]. Sci Rep, 2017, 7(1):10731.〖ZK)〗 [11] 石格,毛志敏,万毅刚,等. 糖尿病肾病足细胞损伤的病理机制及中药的干预作用[J]. 中国中药杂志,2016,41(13):24162418.〖ZK)〗 [12] KWON SH, OH S, NACKE M, et al. Adaptor protein CD2AP and Ltype lectin LMAN2 regulate exosome cargo protein trafficking through the golgi complex[J]. J Biol Chem, 2016, 291(49):2546225475.〖ZK)〗
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