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肉桂醛对烟曲霉细胞壁的影响及其在侵袭性肺曲霉病小鼠治疗中的应用

Effects of Cinnamaldehyde on the Cell Wall of and Its Application in Treating Mice with Invasive Pulmonary Aspergillosis.

作者信息

Deng Jiehua, Wang Gangsheng, Li Jihong, Zhao Yile, Wang Xiaolu

机构信息

Department of Dermatology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.

Research Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.

出版信息

Evid Based Complement Alternat Med. 2018 Oct 4;2018:5823209. doi: 10.1155/2018/5823209. eCollection 2018.

DOI:10.1155/2018/5823209
PMID:30402129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6193338/
Abstract

BACKGROUND

The invasive pulmonary aspergillosis is a kind of high incidence of disease with difficulties in treatment, poor prognosis, and high mortality.

OBJECTIVES

The study aimed to reveal the effect of cinnamaldehyde on the fungal cell wall and verify its efficacy on invasive pulmonary aspergillosis on immunosuppressed Institute of Cancer Research mice (ICR mice).

METHODS

ICR mice were given cyclophosphamide 200 mg.kg. d by intraperitoneal injection for 2 days. On the 4th day, the mice were given 50 of spore (10colony form unit CFU/mL) by intranasal injection to establish immunosuppressive animal models with invasive infection. Then the mice in treatment group orally administered cinnamaldehyde for 14 consecutive days, while voriconazole was given to the mice in the positive control group.

RESULTS

The clearance rate of pulmonary fungi, cure rate, and reduction of 1,3---glucans in treatment group were 80.00%, 80.00%, and 81.00%, respectively while in positive control group they were 67.00%, 60.00%, and 62.00%, respectively. There were significant differences in the results between two groups as mentioned above (P<0.05). Electron microscopy showed that, in treatment group, the cell wall of was dissolved and detached and the cell surface was incomplete. There were edema, degeneration, and necrosis in nucleus and organelle, which lead to cellular necrocytosis. The cytomembrane of was intact, clear, and complete, whereas the cytomembrane in the positive control group disappeared. The hyphal morphology of was deformed, but the cell wall was intact.

CONCLUSION

Cinnamaldehyde has a good curative effect in the treatment of invasive pulmonary aspergillus infection in immunodeficient mice. It mainly affects the synthesis of 1,3---glucans from the cytoderm of but does not affect cell wall. It would potentially be an effective and novel drug for targeted treatment of deep infection.

摘要

背景

侵袭性肺曲霉病是一种发病率高、治疗困难、预后差且死亡率高的疾病。

目的

本研究旨在揭示肉桂醛对真菌细胞壁的作用,并验证其对免疫抑制的癌症研究所小鼠(ICR小鼠)侵袭性肺曲霉病的疗效。

方法

对ICR小鼠腹腔注射环磷酰胺200mg·kg·d,连续2天。第4天,通过滴鼻给予小鼠50μL孢子(10⁶菌落形成单位CFU/mL)以建立侵袭性感染的免疫抑制动物模型。然后治疗组小鼠连续14天口服肉桂醛,阳性对照组小鼠给予伏立康唑。

结果

治疗组肺真菌清除率、治愈率和1,3-β-葡聚糖降低率分别为80.00%、80.00%和81.00%,而阳性对照组分别为67.00%、60.00%和62.00%。上述两组结果存在显著差异(P<0.05)。电子显微镜显示,治疗组中,曲霉的细胞壁溶解、脱落,细胞表面不完整。细胞核和细胞器出现水肿、变性和坏死,导致细胞坏死。曲霉的细胞膜完整、清晰且完整,而阳性对照组的细胞膜消失。曲霉的菌丝形态变形,但细胞壁完整。

结论

肉桂醛对免疫缺陷小鼠侵袭性肺曲霉感染有良好的治疗效果。它主要影响曲霉细胞壁中1,3-β-葡聚糖的合成,但不影响细胞膜。它可能是一种有效且新型的深部感染靶向治疗药物。

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