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土茯苓通过抑制半胱天冬酶 -3 的激活,保护庆大霉素诱导的肾损伤大鼠免受氧化应激诱导的细胞凋亡。

Rhizoma smilacis glabrae protects rats with gentamicin-induced kidney injury from oxidative stress-induced apoptosis by inhibiting caspase-3 activation.

作者信息

Liu Cuiyan, Kang Youxi, Zhou Xiuhong, Yang Zisheng, Gu Jingang, Han Chunyang

机构信息

College of Animal Science and Technology, Anhui Agricultural University, 130 West Changjiang Road, Shushan District, Anhui 230036, PR China.

Biotechnology Center, Anhui Agricultural University, 130 West Changjiang Road, Shushan District, Heifei, Anhui 230036, PR China.

出版信息

J Ethnopharmacol. 2017 Feb 23;198:122-130. doi: 10.1016/j.jep.2016.12.034. Epub 2016 Dec 27.

DOI:10.1016/j.jep.2016.12.034
PMID:28034658
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Rhizoma smilacis glabrae (RSG), which is mild-natured and tastes sweet or bland, has pharmacological action of eliminating dampness, detoxifying, and ensuring that joints were healthy and supple in traditional Chinese medicine.

AIM OF THE STUDY

To discuss the protective effect of RSG on gentamicin (GM)-induced kidney injury in rats and its regulatory mechanisms of oxidative stress-induced apoptosis by inhibiting caspase-3 activation.

MATERIALS AND METHODS

A total of 40 Sprague-Dawley (SD) rats were randomly divided into 5 groups: control group, model group, and RSG low, middle, and high dose groups (0.75,1.5,3gkg). Six hours after intramuscular GM injections, rats in the model group were given distilled water by intragastric administration, and rats in the 3 RSG intervention groups were given different dosages of RSG water-extracts. Twenty-four hours after the last administration, blood and kidney samples were collected to test for biochemical indexes of kidney injury, oxidative stress, histopathological defects, apoptosis rate, and caspase-3 protein expression to assess the protective effect of RSG water-extracts against GM-induced kidney injury.

RESULTS

Compared with the model group, serum TP and ALB levels were significantly higher (P<0.05), and BUN, CRE, and UA levels were significantly lower (P<0.05) in the 3 RSG intervention groups. In kidney tissues, SOD, CAT, and GSH levels increased significantly (P<0.05), while MDA level decreased significantly (P<0.05). Total apoptosis rate dropped markedly (P<0.01), and the protein expressions of caspase-3 increased, while expressions of activated caspase-3 decreased. Histopathological analysis showed shrinkage of kidney cells reduced with appearance of complete kidney structure and decrease in activated caspase-3 expressions in impaired renal tubules decreased. Among the 3 RSG intervention groups, the middle dose group (1.5gkg) showed the best protective effect.

CONCLUSIONS

RSG water-extracts had protective effects against GM-induced kidney injury in rats, and its mechanism of action was related to oxidative stress-induced apoptosis by inhibiting caspase-3 activation.

摘要

民族药理学相关性

土茯苓味甘淡,性平,在传统中医中具有祛湿、解毒以及使关节健康灵活的药理作用。

研究目的

探讨土茯苓对庆大霉素(GM)诱导的大鼠肾损伤的保护作用及其通过抑制半胱天冬酶 -3激活对氧化应激诱导凋亡的调控机制。

材料与方法

将40只Sprague-Dawley(SD)大鼠随机分为5组:对照组、模型组以及土茯苓低、中、高剂量组(0.75、1.5、3 g/kg)。肌肉注射GM 6小时后,模型组大鼠灌胃给予蒸馏水,3个土茯苓干预组大鼠分别给予不同剂量的土茯苓水提取物。末次给药24小时后,采集血液和肾脏样本,检测肾损伤、氧化应激、组织病理学缺陷、凋亡率及半胱天冬酶 -3蛋白表达的生化指标,以评估土茯苓水提取物对GM诱导的肾损伤的保护作用。

结果

与模型组相比,3个土茯苓干预组血清总蛋白(TP)和白蛋白(ALB)水平显著升高(P<0.05),血尿素氮(BUN)、肌酐(CRE)和尿酸(UA)水平显著降低(P<0.05)。在肾组织中,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽(GSH)水平显著升高(P<*0.05),而丙二醛(MDA)水平显著降低(P<0.05)。总凋亡率显著下降(P<0.01),半胱天冬酶 -3蛋白表达增加,而活化的半胱天冬酶 -3表达降低。组织病理学分析显示肾细胞萎缩减轻,肾结构完整,受损肾小管中活化的半胱天冬酶 -3表达减少。在3个土茯苓干预组中,中剂量组(1.5 g/kg)显示出最佳保护效果。

结论

土茯苓水提取物对GM诱导的大鼠肾损伤具有保护作用,其作用机制与通过抑制半胱天冬酶 -3激活减轻氧化应激诱导的凋亡有关。

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