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盐酸米诺环素纳米脂质体抑制 LPS 刺激的巨噬细胞中 TNF-α 的产生。

Minocycline hydrochloride nanoliposomes inhibit the production of TNF-α in LPS-stimulated macrophages.

机构信息

Shandong Provincial Key Laboratory of Oral Biomedicine, College of Stomatology, Shandong University, Shandong Province, People's Republic of China.

出版信息

Int J Nanomedicine. 2012;7:4769-75. doi: 10.2147/IJN.S34036. Epub 2012 Aug 31.

Abstract

BACKGROUND

As an adjunctive treatment of chronic periodontitis, it seems that the application of periocline or the other antimicrobials is effective against periodontopathogens. In this study, nanoliposomes were investigated as carriers of minocycline hydrochloride and the inhibition effects of minocycline hydrochloride nanoliposomes on the proliferation and lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α) of macrophages were elucidated.

METHODS

After stimulation with 10 μg/mL LPS, murine macrophages (ANA-1) were treated with 10, 20, 40, 50 and 70 μg/mL 2% minocycline hydrochloride nanoliposomes, minocycline hydrochloride solution, and periocline for 6, 12, 24, 48 and 60 hours, respectively. A tetrazolium (MTT) assay was used to evaluate macrophages cell proliferation rate and the levels of TNF-α mRNA were measured by SYBR Green Real Time PCR.

RESULTS

Ten to 70 μg/mL 2% minocycline hydrochloride nanoliposomes, minocycline hydrochloride solution, and periocline showed dose- and time-dependent inhibition of ANA-1 proliferation. Minocycline hydrochloride nanoliposomes showed dose- and ratio-dependent inhibition of LPS-stimulated TNF-α secretion of ANA-1. The inhibition effect of 10 μg/mL minocycline hydrochloride nanoliposomes was significantly better than that of two positive control groups, and equated to that of 60 or 70 μg/mL periocline. The expression of TNF-α mRNA in experimental group continued to reduce linearly with time.

CONCLUSION

All three preparations of minocycline hydrochloride showed dose- and time-dependent inhibition of proliferation of ANA-1. Minocycline hydrochloride nanoliposomes have stronger and longer inhibition effect on LPS-stimulated TNF-α secretion of macrophages cell than minocycline hydrochloride solution and periocline.

摘要

背景

作为慢性牙周炎的辅助治疗方法,应用派利奥或其他抗菌药物似乎对牙周致病菌有效。在本研究中,我们研究了纳米脂质体作为盐酸米诺环素的载体,以及盐酸米诺环素纳米脂质体对巨噬细胞增殖和脂多糖(LPS)刺激的肿瘤坏死因子-α(TNF-α)产生的抑制作用。

方法

用 10μg/mlLPS 刺激后,用 10、20、40、50 和 70μg/ml2%盐酸米诺环素纳米脂质体、盐酸米诺环素溶液和派利奥分别处理巨噬细胞(ANA-1)6、12、24、48 和 60 小时。四唑(MTT)法检测巨噬细胞增殖率,SYBR Green 实时 PCR 法检测 TNF-αmRNA 水平。

结果

10 至 70μg/ml2%盐酸米诺环素纳米脂质体、盐酸米诺环素溶液和派利奥对 ANA-1 增殖均表现出剂量和时间依赖性抑制作用。盐酸米诺环素纳米脂质体对 LPS 刺激的 ANA-1 分泌 TNF-α具有剂量和比例依赖性抑制作用。10μg/ml 盐酸米诺环素纳米脂质体的抑制效果明显优于两个阳性对照组,与 60 或 70μg/ml 派利奥相当。实验组 TNF-αmRNA 的表达随时间呈线性持续下降。

结论

三种盐酸米诺环素制剂对 ANA-1 的增殖均表现出剂量和时间依赖性抑制作用。盐酸米诺环素纳米脂质体对 LPS 刺激的巨噬细胞 TNF-α分泌的抑制作用强于盐酸米诺环素溶液和派利奥。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbe/3433324/0bc9d85596d4/ijn-7-4769f1.jpg

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