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巴西钝眼蜱(mouro tick)唾液腺匀浆物抑制体内伤口愈合和体外内皮细胞增殖。

Ornithodoros brasiliensis (mouro tick) salivary gland homogenates inhibit in vivo wound healing and in vitro endothelial cell proliferation.

机构信息

Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF), Fundação Estadual de Pesquisa Agropecuária (FEPAGRO), Eldorado do Sul, RS, Brazil.

出版信息

Parasitol Res. 2013 Apr;112(4):1749-53. doi: 10.1007/s00436-013-3333-3. Epub 2013 Feb 9.

DOI:10.1007/s00436-013-3333-3
PMID:23397378
Abstract

Ornithodoros brasiliensis is a nidicolous tick only found in the southern Brazilian highlands region. O. brasiliensis parasitism is frequently associated with toxicosis syndrome, which can lead to severe reactions, ranging from local pruritus and pain to systemic disturbances both in humans and dogs. One of the most frequent findings associated with an O. brasiliensis bite is a slow healing lesion at the site of tick attachment, which can take several weeks to heal. This work tested the hypothesis that an O. brasiliensis salivary gland homogenate is able to modulate the skin wound-healing process in vivo, using a model of excisional skin lesion in rats, which are divided into two groups: (1) control group and (2) treated group, which topically received salivary gland homogenate equivalent to the protein amount of one whole salivary gland (≈5 μg protein). The hypothesis that O. brasiliensis salivary gland homogenates interfere with endothelial cell proliferation, a key role phenomenon in wound healing, was also tested. O. brasiliensis salivary gland homogenates significantly delay skin wound healing. The time to full healing of skin lesions in control rats was 15 days, contrasting with 24 days in rats topically treated with O. brasiliensis salivary gland homogenates. The calculated HT50 (healing time to recover 50% of the wound area) for control groups was 3.6 days (95% CI, 3.2-3.9) and for salivary gland treated rats was 7.7 days (95% CI, 7.0-8.4). Salivary gland homogenates have a strong cytotoxic activity on cultured endothelial cells (LC50, 13.6 mg/ml). Also, at sublethal concentrations (≤3 mg/ml), salivary gland homogenates have a remarkable anti-proliferative activity (IC50 0.7 mg/ml) on endothelial cells, equivalent to ≈0.03 salivary gland pairs, an activity which seems to be much greater than reported for any other tick species. This is the first report about the biological activities of O. brasiliensis salivary compounds and provides the first in vivo evidence to support the concept of wound-healing modulation by tick salivary secretions. Results shown here contribute to an understanding of O. brasiliensis tick toxicosis syndrome, and also increase our knowledge of tick salivary bioactive compounds.

摘要

巴西革蜱是一种仅在巴西南部高地发现的嗜血性蜱。巴西革蜱寄生常与中毒综合征相关,这可能导致人类和犬类出现严重反应,包括局部瘙痒和疼痛以及全身性紊乱。与巴西革蜱叮咬最相关的一种常见发现是蜱附着部位的缓慢愈合损伤,可能需要数周才能愈合。本工作通过大鼠皮肤切除损伤模型,检验了巴西革蜱唾液腺匀浆能够调节体内皮肤伤口愈合过程的假说,该模型分为两组:(1)对照组和(2)实验组,实验组局部给予相当于一个完整唾液腺的蛋白量(≈5 μg 蛋白)的唾液腺匀浆。还检验了巴西革蜱唾液腺匀浆干扰内皮细胞增殖(伤口愈合的关键作用现象)的假说。巴西革蜱唾液腺匀浆显著延迟皮肤伤口愈合。对照组大鼠皮肤损伤完全愈合的时间为 15 天,而局部给予巴西革蜱唾液腺匀浆的大鼠则为 24 天。对照组的 HT50(恢复伤口面积 50%的愈合时间)为 3.6 天(95%CI,3.2-3.9),而唾液腺处理的大鼠为 7.7 天(95%CI,7.0-8.4)。唾液腺匀浆对培养的内皮细胞具有很强的细胞毒性(LC50,13.6mg/ml)。此外,在亚致死浓度(≤3mg/ml)下,唾液腺匀浆对内皮细胞具有显著的抗增殖活性(IC50 0.7mg/ml),相当于≈0.03 个唾液腺对,这种活性似乎比任何其他蜱种报道的都大。这是首次报道巴西革蜱唾液化合物的生物学活性,并为蜱唾液分泌物调节伤口愈合提供了首个体内证据。这里展示的结果有助于了解巴西革蜱中毒综合征,并增加我们对蜱唾液生物活性化合物的认识。

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