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评价载有和未载有辛伐他汀的根管封闭剂的细胞毒性和细胞因子 IL-6 产生:一项体外研究。

The evaluation of cytotoxicity and cytokine IL-6 production of root canal sealers with and without the incorporation of simvastatin: an invitro study.

机构信息

Department of Conservative Dentistry and Endodontics, SRM Dental College, Ramapuram, Chennai, Tamil Nadu, 600089, India.

出版信息

BMC Oral Health. 2022 Jan 11;22(1):6. doi: 10.1186/s12903-022-02039-y.

DOI:10.1186/s12903-022-02039-y
PMID:35012572
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8751161/
Abstract

BACKGROUND

Freshly mixed root canal sealers when proximate the periapical tissues, trigger varying degrees of cytotoxicity/inflammatory reactions. Simvastatin, a class of the drug statin, is a widely used cholesterol-lowering agent with additional anti-inflammatory activities. This study assessed the effects of simvastatin on cytotoxicity and the release of IL-6 (Interleukin-6) production when incorporated in zinc oxide eugenol and methacrylate resin-based sealers.

METHODS

Experimental groups consisted of conventional zinc oxide eugenol and methacrylate based-EndoREZ sealers (ZE & ER respectively) and 0.5 mg/mL simvastatin incorporated sealers (ZES & ERS). L929 mouse fibroblast cells were exposed to freshly mixed experimental sealers and evaluated for cytotoxicity (MTT assay) and inflammation levels (inflammatory marker IL-6 for ELISA) at various time intervals (0h, 24h and 7th day). The values were compared to the cell control (CC; L929 cells alone) and solvent control (SC; L929 cells + DMSO) groups. All the experiments were conducted in triplicates and subjected to statistical analysis using IBM SPSS Statistics software. Non parametric tests were conducted using Kruskal-Wallis and Friedman tests for inter-group and intra-group comparisons respectively. Pairwise comparison was conducted by post hoc Dunn test followed by Bonferroni correction. P values < 0.05 were considered statistically significant.

RESULTS

All the experimental groups (ZE, ER, ZES, ERS) exhibited varying degree of cytotoxicity and IL-6 expression compared to the control groups CC and SC. The cell viability for ZE and ER decreased on day 7 as compared to 24 h. ZES and ERS had higher viable cells (75.93% & 79.90%) compared to ZE and ER (54.39% & 57.84%) at all time periods. Increased expression of IL-6 was observed in ZE & ER (25.49 pg/mL & 23.14 pg/mL) when compared to simvastatin incorporated ZE & ER (ZES-12.70 pg/mL & ERS-14.68 pg/mL) at all time periods. Highest level of cytotoxicity and inflammation was observed in ZE compared to all the other groups on day 7.

CONCLUSIONS

Addition of 0.5 mg/mL of simvastatin to the sealers (ZES and ERS) decreased the cytotoxicity in the freshly mixed state and reduces their inflammatory effect.

摘要

背景

新混合的根管封闭剂接近根尖周组织时,会引发不同程度的细胞毒性/炎症反应。辛伐他汀是他汀类药物的一种,是一种广泛使用的降胆固醇药物,具有额外的抗炎作用。本研究评估了辛伐他汀对氧化锌丁香酚和甲基丙烯酸树脂基封闭剂的细胞毒性和白细胞介素-6(IL-6)产生的影响。

方法

实验组包括传统的氧化锌丁香酚和甲基丙烯酸酯基-EndoREZ 封闭剂(ZE 和 ER 分别)和 0.5mg/mL 辛伐他汀掺入的封闭剂(ZES 和 ERS)。L929 小鼠成纤维细胞暴露于新混合的实验封闭剂中,并在不同时间间隔(0h、24h 和 7 天)评估细胞毒性(MTT 测定)和炎症水平(酶联免疫吸附试验中的炎症标志物 IL-6)。将这些值与细胞对照(CC;单独的 L929 细胞)和溶剂对照(SC;L929 细胞+DMSO)组进行比较。所有实验均重复三次,并使用 IBM SPSS Statistics 软件进行统计分析。使用 Kruskal-Wallis 和 Friedman 检验分别进行组间和组内比较的非参数检验。通过事后 Dunn 检验和 Bonferroni 校正进行两两比较。P 值<0.05 被认为具有统计学意义。

结果

与对照 CC 和 SC 相比,所有实验组(ZE、ER、ZES、ERS)均表现出不同程度的细胞毒性和 IL-6 表达。ZE 和 ER 的细胞活力在第 7 天比 24 小时下降。ZES 和 ERS 在所有时间段的存活细胞(75.93%和 79.90%)均高于 ZE 和 ER(54.39%和 57.84%)。与掺入辛伐他汀的 ZE 和 ER(ZES-12.70pg/mL 和 ERS-14.68pg/mL)相比,在所有时间点,ZE 和 ER 中观察到更高的白细胞介素-6 表达(25.49pg/mL 和 23.14pg/mL)。在第 7 天,与所有其他组相比,ZE 观察到最高水平的细胞毒性和炎症。

结论

在封闭剂(ZES 和 ERS)中添加 0.5mg/mL 的辛伐他汀可降低新混合状态下的细胞毒性,并降低其炎症作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e2/8751161/fbbc76a9ea40/12903_2022_2039_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e2/8751161/fbbc76a9ea40/12903_2022_2039_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e2/8751161/3bf724356e1a/12903_2022_2039_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e2/8751161/008b3ef7ab26/12903_2022_2039_Fig2_HTML.jpg
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