卡介菌多糖核酸注射液靶向瞬时受体电位香草酸亚型1通路对特应性皮炎的干预作用及机制研究

Study on the intervention effect and mechanism of bacillus Calmette-Guerin polysaccharide and nucleic acid injection on atopic dermatitis by targeting the transient receptor potential vanilloid subtype 1 pathway.

作者信息

Wang Xiufen, Wu Di, Duan Tingting, Liu Ying, Lv Shukun, Cui Liran, Ding Changrui, Xu Yulong

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

Scientific Research Section, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

出版信息

Ann Transl Med. 2022 May;10(10):608. doi: 10.21037/atm-22-2101.

DOI:10.21037/atm-22-2101

PMID:35722408

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9201144/

Abstract

BACKGROUND

This study aimed to explore the mechanism of Bacillus Calmette-Guerin polysaccharide and nucleic acid injection (BCG-PSN) targeting the transient receptor potential vanilloid subtype 1 (TRPV1) pathway for atopic dermatitis (AD) in mice.

METHODS

Experiment 1: a total of 30 Kunming (KM) mice were randomized into blank control, model, BCG-PSN low-dose (25 g/kg), BCG-PSN medium-dose (75 g/kg), BCG-PSN high-dose (225 g/kg), and positive drug (hydrocortisone 25 mg/kg) control groups. The AD model mice were established by induction with 2,4-Dinitrochlorobenzene (DNCB). After treatment in groups, the symptom score and scratching frequency in skin lesions were observed. The levels of immunoglobulin E (IgE), interleukin (IL)-4, IL-31, and IL-13 in serum were detected, as well as the levels of tumor necrosis factor-α (TNF-α), TRPV1, and nuclear factor (NF)-κB p65 in skin lesions in each group. Experiment 2: the optimal dose of BCG-PSN in Experiment 1 was adopted. A total of 20 KM mice were randomized into blank control, model, BCG-PSN, and BCG-PSN + PAC (PAC-14028) groups. The symptom score and scratching frequency in skin lesions were observed. The levels of IgE, IL-4, IL-31, and IL-13 in serum were detected, as well as the levels of TNF-α and TRPV1 in skin lesions in each group.

RESULTS

In Experiment 1, compared with the blank control group, the ear tissues of mice in model groups developed AD, with increased symptom score, scratching frequency, levels of IgE, IL-4, IL-31, and IL-13 in serum and levels of TNF-α, TRPV1, and NF-κB p65 in skin lesions. Compared with the model group, BCG-PSN low-dose, BCG-PSN medium-dose, BCG-PSN high-dose, and positive drug control groups had reduced AD symptoms, decreased symptom score, and decreased scratching frequency, with declined expression of each inflammatory substance, including the greatest decrease in the medium-dose group. In Experiment 2, after BCG-PSN was combined with PAC, the inflammation indexes decreased compared with those in the model group, and increased compared with those in the BCG-PSN group.

CONCLUSIONS

Intramuscular BCG-PSN can target the TRPV1 pathway, inhibit inflammation, and improve the symptoms of AD mice.

摘要

背景

本研究旨在探讨卡介菌多糖核酸注射液（BCG-PSN）针对小鼠特应性皮炎（AD）靶向瞬时受体电位香草酸亚型1（TRPV1）通路的机制。

方法

实验1：将30只昆明（KM）小鼠随机分为空白对照组、模型组、BCG-PSN低剂量（25μg/kg）组、BCG-PSN中剂量（75μg/kg）组、BCG-PSN高剂量（225μg/kg）组和阳性药物（氢化可的松25mg/kg）对照组。用2,4-二硝基氯苯（DNCB）诱导建立AD模型小鼠。分组处理后，观察皮肤病变的症状评分和搔抓频率。检测血清中免疫球蛋白E（IgE）、白细胞介素（IL）-4、IL-31和IL-13的水平，以及各组皮肤病变中肿瘤坏死因子-α（TNF-α）、TRPV1和核因子（NF）-κB p65的水平。实验2：采用实验1中BCG-PSN的最佳剂量。将20只KM小鼠随机分为空白对照组、模型组、BCG-PSN组和BCG-PSN+PAC（PAC-14028）组。观察皮肤病变的症状评分和搔抓频率。检测血清中IgE、IL-4、IL-31和IL-13的水平，以及各组皮肤病变中TNF-α和TRPV1的水平。

结果

实验1中，与空白对照组相比，模型组小鼠耳部组织出现AD，症状评分、搔抓频率、血清中IgE、IL-4、IL-31和IL-13水平以及皮肤病变中TNF-α、TRPV1和NF-κB p65水平均升高。与模型组相比，BCG-PSN低剂量组、BCG-PSN中剂量组、BCG-PSN高剂量组和阳性药物对照组的AD症状减轻，症状评分降低，搔抓频率降低，各炎症物质表达下降，其中中剂量组下降最为明显。实验2中，BCG-PSN与PAC联合使用后，炎症指标与模型组相比降低，与BCG-PSN组相比升高。