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甘草次酸脂质体通过抑制炎症应激对环磷酰胺诱导的膀胱炎的细胞保护作用。

Cytoprotective effects of glycyrrhetinic acid liposome against cyclophosphamide-induced cystitis through inhibiting inflammatory stress.

机构信息

Department of Urology Surgery, Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, PR China.

Department of Pathology, Guigang City People's Hospital, Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi 537100, PR China.

出版信息

Int Immunopharmacol. 2018 Jan;54:139-144. doi: 10.1016/j.intimp.2017.11.010. Epub 2017 Nov 11.

Abstract

This study was designed to investigate the pharmacological efficacy of glycyrrhetinic acid liposome (GAL) against female mice with nonbacterial cystitis induced by cyclophosphamide (CPS). Mice in different groups were subjected to tests for lactate dehydrogenase (LD), cytokine contents (IL-6, TNF-α) in serum, and histological changes in bladder tissue and to immunoassays. As a result, cyclophosphamide-induced cystitis in mice showed an increased LD level in serum, and the contents of cytokines (IL-6, TNF-α) were elevated. Interestingly, GAL-treated mice showed decreased LD and inflammatory cytokines of IL-6 and TNF-α in blood. Inflammatory infiltration and cell death in bladder tissue were reduced by GAL treatments. In addition, intravesical mRNAs of NF-κB and TNF-α were lowered dose-dependently in GAL-treated mice. As shown in cytohistological staining, the number of intravesical caspase-3, PARP-positive cells decreased in GAL-treated mice. Furthermore, a GAL-treated bladder showed down-regulated NF-κB and TNF-α expressions in a dose-dependent manner. In conclusion, our current findings may be the first to provide scientific evidence demonstrating that glycyrrhetinic acid liposomes provide benefits against cyclophosphamide-induced cystitis, which possibly occurs through underlying mechanisms that inhibit cell death and inflammatory stress.

摘要

本研究旨在探讨甘草次酸脂质体(GAL)对环磷酰胺(CPS)诱导的非细菌性膀胱炎雌性小鼠的药理作用。不同组别的小鼠接受乳酸脱氢酶(LD)、血清细胞因子含量(IL-6、TNF-α)、膀胱组织学变化和免疫检测。结果显示,环磷酰胺诱导的小鼠膀胱炎表现为血清 LD 水平升高,细胞因子(IL-6、TNF-α)含量升高。有趣的是,GAL 治疗组小鼠的血液中 LD 和促炎细胞因子 IL-6 和 TNF-α降低。GAL 治疗还可减轻膀胱组织的炎症浸润和细胞死亡。此外,GAL 治疗组小鼠膀胱内 NF-κB 和 TNF-α的 mRNA 水平呈剂量依赖性降低。细胞组织化学染色显示,GAL 治疗组小鼠膀胱内 caspase-3、PARP 阳性细胞数量减少。此外,GAL 治疗的膀胱呈剂量依赖性下调 NF-κB 和 TNF-α的表达。综上所述,本研究结果首次提供了科学证据,表明甘草次酸脂质体对环磷酰胺诱导的膀胱炎具有治疗作用,其作用机制可能是通过抑制细胞死亡和炎症应激来实现的。

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