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积雪草苷对阿霉素诱导的大鼠肾病中足细胞细胞骨架蛋白和肾小裂隙隔膜蛋白水平的影响。

Effects of asiaticoside on levels of podocyte cytoskeletal proteins and renal slit diaphragm proteins in adriamycin-induced rat nephropathy.

机构信息

Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China.

出版信息

Life Sci. 2013 Sep 3;93(8):352-8. doi: 10.1016/j.lfs.2013.07.010. Epub 2013 Jul 18.

Abstract

AIMS

Centella asiatica has been used to treat kidney diseases in Chinese traditional medicine. Asiaticoside (an extraction of C. asiatica) exerts a variety of pharmacological effects including immunomodulatory and anti-inflammatory functions. However, the mechanism of asiaticoside in the treatment of renal diseases remains largely unknown. This study investigated the molecular mechanism of asiaticoside in treating adriamycin-induced nephropathy of rats.

MAIN METHODS

Sixty-two SD male rats were randomly divided into normal control group (n=12) and nephropathy group (n=50). Except for the normal control group, rats were injected with adriamycin (6mg/kg) via the tail vein to induce nephropathy. Adriamycin induced nephropathic rats were divided into untreated group, prednisone group (25mg/kg), and asiaticoside groups with various dosages (8, 16 and 32mg/kg). Samples of urine and serum, tissue of kidney were collected for analysis after treatments for four weeks. Morphological changes were evaluated under light microscope and electron microscope. Synaptopodin, desmin, nephrin and podocin mRNA and protein were determined by RT-PCR and Western blotting.

KEY FINDINGS

Compared to the untreated nephropathy group, asiaticoside treatment mitigated histological damages, decreased 24-hour urine protein excretion and total cholesterol, increased serum albumin. Asiaticoside treatment increased the mRNA and protein levels of synaptopodin, nephrin and podocin in a dose-dependent manner. Furthermore, asiaticoside treatment decreased the mRNA and protein levels of desmin.

SIGNIFICANCE

Asiaticoside can mitigate adriamycin-induced nephropathy in rats, which is associated with the increase in synaptopodin, nephrin and podocin gene expression, and the decrease in desmin gene expression.

摘要

目的

积雪草在中医中被用于治疗肾脏疾病。积雪草酸(积雪草的一种提取物)具有多种药理作用,包括免疫调节和抗炎作用。然而,积雪草酸治疗肾脏疾病的机制在很大程度上尚不清楚。本研究旨在探讨积雪草酸治疗阿霉素诱导的大鼠肾病的分子机制。

方法

62 只雄性 SD 大鼠随机分为正常对照组(n=12)和肾病组(n=50)。除正常对照组外,其余大鼠均通过尾静脉注射阿霉素(6mg/kg)诱导肾病。将阿霉素诱导的肾病大鼠分为未治疗组、泼尼松组(25mg/kg)和不同剂量(8、16 和 32mg/kg)的积雪草酸组。治疗 4 周后收集尿液和血清样本及肾脏组织进行分析。在光镜和电子显微镜下评估形态学变化。通过 RT-PCR 和 Western blot 测定突触蛋白、结蛋白、nephrin 和 podocin 的 mRNA 和蛋白表达。

结果

与未治疗的肾病组相比,积雪草酸治疗减轻了组织学损伤,降低了 24 小时尿蛋白排泄和总胆固醇,增加了血清白蛋白。积雪草酸治疗呈剂量依赖性增加 synaptopodin、nephrin 和 podocin 的 mRNA 和蛋白水平。此外,积雪草酸治疗降低了结蛋白的 mRNA 和蛋白水平。

结论

积雪草酸可减轻阿霉素诱导的大鼠肾病,其机制与 synaptopodin、nephrin 和 podocin 基因表达增加以及结蛋白基因表达减少有关。

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