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[含黄酮的水苋菜提取物给药对移植性大鼠肾癌中凋亡和自噬标志物表达的影响]

[The expression of apoptosis and autophagy markers in transplantable rat kidney cancer with the administration of flavonoid-containing hedge hyssop ( L.) extract].

作者信息

Navolokin N A, Maslyakova G N, Polukonova N V, Mudrak D A, Bucharskaya A B

机构信息

V.I. Razumovsky Saratov State Medical University, Ministry of Health of Russia, Saratov, Russia.

出版信息

Arkh Patol. 2019;81(1):24-30. doi: 10.17116/patol20198101124.

DOI:10.17116/patol20198101124
PMID:30830101
Abstract

OBJECTIVE

To establish the mechanisms of pathomorphism of transplantable kidney cancer in rats that used flavonoid-containing hedge hyssop (Gratiola officinalis L.) extract in an in vivo experiments.

MATERIAL AND METHODS

The experiment was carried out on 30 male Wistar rats with transplantable kidney cancer PA. At 72 hours after tumor inoculation, the rats in the experimental groups received hedge hyssop extract at an oral or intramuscular dose of 110 mg/kg/day for 12 days. A comparison group consisted of the animals with a tumor, but without exposure. The investigators used the immunohistochemical markers of apoptosis (p53, bax, bcl-2, Fas-receptor, Fas-ligand), autophagy (LC3B), proliferation (Ki-67), and angiogenesis (VEGF). During statistical data processing, the Shapiro-Wilk test was used to test the normality of the indicator distribution in the groups. Cramer-Welch's t-test was also employed to compare the groups.

RESULTS

Histological examination of tumor tissue under the action of hedge hyssop extract showed the emergence of extensive areas of damage (necrosis and apoptotic bodies). With both routes of hedge hyssop extract administration, there was a sharp decrease in the expression of the proliferation markers Ki-67 and the angiogenesis marker VEGF and a high expression of the apoptosis markers p53, bax, CD95 (Fas/APO-1), and FAS-ligand in tumor cells and its absence in the comparison group. All the described changes were more pronounced with intramuscular administration. The expression of the autophagy marker LC3B increased with the oral administration of hedge hyssop extract and decreased with its intramuscular administration.

CONCLUSION

A pronounced pathomorphism of kidney cancer develops due to consumption of hedge hyssop extract. This suppresses the proliferation, angiogenesis, and activation of apoptotic signaling and mitochondrial pathways and blocks protective autophagy. The autophagy marker LC3B can be used as an additional criterion for evaluating the therapeutic pathomorphism of tumors.

摘要

目的

通过体内实验,确定含黄酮类的水八角(水八角)提取物对大鼠移植性肾癌病理形态变化机制的影响。

材料与方法

对30只患有移植性肾癌PA的雄性Wistar大鼠进行实验。在接种肿瘤72小时后,实验组大鼠以口服或肌肉注射的方式,每天给予110mg/kg剂量的水八角提取物,持续12天。对照组由患有肿瘤但未接受处理的动物组成。研究人员使用了凋亡(p53、bax、bcl-2、Fas受体、Fas配体)、自噬(LC3B)、增殖(Ki-67)和血管生成(VEGF)的免疫组化标记物。在统计数据处理过程中,使用Shapiro-Wilk检验来检验各组指标分布的正态性。还采用了Cramer-Welch t检验来比较各组。

结果

水八角提取物作用下肿瘤组织的组织学检查显示出现了广泛的损伤区域(坏死和凋亡小体)。通过两种水八角提取物给药途径,肿瘤细胞中增殖标记物Ki-67和血管生成标记物VEGF的表达急剧下降,凋亡标记物p53、bax、CD95(Fas/APO-1)和Fas配体的表达升高,而对照组则无此现象。所有上述变化在肌肉注射时更为明显。自噬标记物LC3B的表达在口服水八角提取物时增加,在肌肉注射时减少。

结论

食用水八角提取物会导致肾癌出现明显的病理形态变化。这抑制了增殖、血管生成以及凋亡信号和线粒体途径的激活,并阻断了保护性自噬。自噬标记物LC3B可作为评估肿瘤治疗病理形态变化的额外标准。

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