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二神丸提取物可缓解脾肾阳虚型腹泻大鼠的多尿,并调节 AQP2 和 AVPR2。

Er Shen Wan extract alleviates polyuria and regulates AQP 2 and AVPR 2 in a rat model of spleen-kidney Yang deficiency-induced diarrhea.

机构信息

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, PR China; College of Pharmacy, Guiyang College of Traditional Chinese Medicine, Guizhou 550002, PR China.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, PR China.

出版信息

Biomed Pharmacother. 2019 Feb;110:302-311. doi: 10.1016/j.biopha.2018.11.147. Epub 2018 Dec 3.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Er Shen Wan (ESW), has been empirically used for treating spleen-kidney Yang deficiency (SKYD) syndrome in Traditional Chinese medicine (TCM) for centuries and shows a variety of activities. The medicinal formula is a mixture of two component herbs, Psoraleae Fructus (PF, Bu-Gu-Zhi in Chinese) and Myristicae Semen (MS, Rou-Dou-Kou in Chinese). The current study was designed to evaluate ESWP antidiuretic treatment of polyuria and to explore potential mechanisms of renal water metabolism in the rat model of SKYD-induced diarrhea.

MATERIALS AND METHODS

An animal model of 'SKYD-induced diarrhea syndrome' has been established to evaluate the therapeutic effect and action mechanism according to the clinical syndrome and symptoms. The optimal dose (3.5 g/kg) of ESWP was given to rats by gavage for two weeks. Urinary volumes after 24 h were recorded. After the end of the trial, macroscopic morphological and histological examination of the kidney were conducted. Serum levels of Arginine vasopressin (AVP) and aldosterone (ALD) were also measured. Additionally, quantitative real-time RT-PCR (RT-qPCR) and immunohistochemistry (IHC) analyses were performed to clarify the regulation of aquaporin 2 (AQP 2) and arginine vasopressin type 2 receptor (AVPR 2) in the kidney at the gene and tissue expression levels respectively.

RESULTS

After the administration of ESWP, urinary output volume after 24 h was found to be significantly decreased in rats. Elevated plasma levels of AVP and ALD were detected. Histological kidney damage appeared to be impeded, and histological disease scores were reduced. In addition, the expression levels of AQP 2 and AVPR 2 were significantly increased.

CONCLUSION

This study suggests that ESWP may elicit significant effects on the treatment of polyuria. Potential mechanisms at least partially involve hormone regulation, and alleviating renal pathological damage. Simultaneously, ESWP may alter renal water absorption by increasing AQP 2 and AVPR 2 expression levels. Thus, the in vivo experimental evidence indicates that ESWP has a therapeutic effect on the SKYD syndrome, which is consistent with its traditional usage.

摘要

民族药理学相关性

二神丸(ESW)在中医临床上已被经验性地用于治疗脾肾阳虚(SKYD)综合征数百年,具有多种活性。该方剂是由两种成分草药组成的混合物,补骨脂(PF,Bu-Gu-Zhi 中文)和肉豆蔻(MS,Rou-Dou-Kou 中文)。本研究旨在评估 ESWP 对多尿的利尿治疗作用,并探索 SKYD 诱导腹泻大鼠模型中肾脏水代谢的潜在机制。

材料与方法

根据临床症状和体征,建立了“SKYD 诱导腹泻综合征”动物模型,以评估治疗效果和作用机制。通过灌胃给予大鼠 ESWP 的最佳剂量(3.5 g/kg),连续两周。记录 24 小时后的尿量。试验结束后,对肾脏进行宏观形态和组织学检查。还测量了血清血管加压素(AVP)和醛固酮(ALD)的水平。此外,通过定量实时 RT-PCR(RT-qPCR)和免疫组织化学(IHC)分析,分别阐明了肾脏水通道蛋白 2(AQP 2)和血管加压素 2 型受体(AVPR 2)在基因和组织表达水平的调节。

结果

给予 ESWP 后,发现大鼠 24 小时后的尿量明显减少。检测到血浆 AVP 和 ALD 水平升高。肾组织损伤得到抑制,组织学疾病评分降低。此外,AQP 2 和 AVPR 2 的表达水平显著增加。

结论

本研究表明,ESWP 可能对多尿症的治疗有显著效果。潜在的机制至少部分涉及激素调节和减轻肾脏病理损伤。同时,ESWP 可能通过增加 AQP 2 和 AVPR 2 的表达水平来改变肾脏的水分吸收。因此,体内实验证据表明,ESWP 对 SKYD 综合征具有治疗作用,这与其传统用途一致。

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