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染料木黄酮对荷淋巴瘤小鼠炎症和血栓形成倾向的体内干预及相关机制

[The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice].

作者信息

Chen Zhi-Yue, Shi Qing-Qing, Sun Xin, Ni Jun, Wu Wei, Shen Lian-Jun, Sun Mei, Xu Kai-Lin, Gu Jian, Gu Hao

机构信息

Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China.

Department of Hematology, Northern People's Hospital, Yangzhou 225001, Jiangsu Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Feb;31(1):125-129. doi: 10.19746/j.cnki.issn.1009-2137.2023.01.020.

Abstract

OBJECTIVE

To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.

METHODS

Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX)drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.

RESULTS

After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all <0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (<0.05).

CONCLUSION

Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

摘要

目的

探讨染料木黄酮(GEN)对荷淋巴瘤小鼠肿瘤相关炎症及肿瘤血栓形成倾向的体内干预作用及相关机制。

方法

将40只5 - 6周龄雌性Balb/c小鼠注射鼠源性前B细胞淋巴瘤细胞系38B9建立淋巴瘤小鼠模型,随机分为对照组、荷瘤组、GEN药物干预组和环磷酰胺(CTX)药物干预组。采用组织病理学评估肿瘤发生情况。观察肿瘤形成情况,收集肿瘤组织进行苏木精-伊红(HE)染色和免疫组化染色。分别采用酶联免疫吸附测定(ELISA)和流式细胞术检测GEN和环磷酰胺(CTX)干预后血浆中炎症因子表达及血栓指标变化。采用免疫组化方法检测荷瘤小鼠肿瘤组织中CD19的表达。

结果

荷瘤14天后,小鼠发生肿瘤。淋巴瘤细胞在肿瘤组织中弥漫分布,肿瘤组织中CD19表达呈阳性。荷淋巴瘤小鼠体内白细胞介素-6(IL-6)、中性粒细胞胞外诱捕网(NETs)、C型凝集素受体2(CLEC-2)等炎症因子以及组织因子(TF)、纤维蛋白原(FIB)、D - 二聚体(D-D)等血栓指标显著高于肿瘤注射前,且低于药物干预后(均P<0.05)。GEN组CLEC-2和D-D水平显著低于CTX组(P<0.05)。

结论

荷淋巴瘤小鼠存在肿瘤相关炎症和血栓形成倾向。GEN通过干扰肿瘤炎症因子,显示出比CTX更好的抗炎和抗血栓作用。

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