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来自阿根廷东北部的异齿游蛇科食螺蛇杜氏腺分泌物的肌肉和皮肤坏死及形成水肿的活性

Muscle and skin necrotizing and edema-forming activities of Duvernoy's gland secretion of the xenodontine colubrid snake Philodryas patagoniensis from the north-east of Argentina.

作者信息

Peichoto M E, Acosta O, Leiva L, Teibler P, Maruñak S, Ruíz R

机构信息

Cátedra de Química Biológica I, Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Av. Libertad 5470, Corrientes 3400, Argentina.

出版信息

Toxicon. 2004 Nov;44(6):589-96. doi: 10.1016/j.toxicon.2004.05.030.

Abstract

Philodryas patagoniensis is a colubrid snake spread by all South America, but very little is known about the composition and biological activities of its Duvernoy's gland secretion. In order to characterize it, we studied edematogenic, dermonecrotic and myonecrotic activities. For edematogenic activity, solutions containing different amounts of secretion were injected s.c. in the right foot pad of mice, both feet were subsequently cut off and weighed individually. For myonecrotic activity, mice were injected i.m. with solutions containing 40 microg of secretion, and at various time intervals mice were bled to determine serum creatine kinase activity and gastrocnemius muscles were removed for microscopic examination (Hematoxylin-Eosin stain). For dermonecrotic activity, solutions containing different amounts of secretion were injected into the shaved dorsal skin of mice; the necrotic lesion was measured on the inner surface of the skin and trimmed for microscopic examination (Hematoxylin-Eosin stain). Phospholipase A(2) activity was evaluated using a kinetic method. Results showed that P. patagoniensis Duvernoy's gland secretion exhibits a high edematogenic activity and moderate myonecrotic and dermonecrotic activities, while lacking phospholipase A(2) effect. Regarding edema, a 30% increase in the weight was produced by injecting 0.26 microg of Duvernoy's gland secretion. Microscopically, myonecrosis reached its highest intensity 12 h after injection, which was also demonstrated by serum creatine kinase levels. Dermonecrosis was proportional to the amount of secretion injected, with a minimum necrotizing dose of 15.7 microg. Myonecrotic, edematogenic and dermonecrotic activities were inhibited when the secretion was pre-incubated with 1 mM Na(2)EDTA. This suggests that the enzymes responsible for those activities are mostly metalloproeinases. All the studies carried out up to now demonstrate the potential toxicity of P. patagoniensis Duvernoy's gland secretion (which inhabits the north-east region of Argentina) and that the local lesions caused by this colubrid snake are very similar to those found in bothropic accidents. This latter suggests a more careful evaluation of the victims when considering the medical treatment to be adopted.

摘要

巴塔哥尼亚菲洛德蛇是一种分布于南美洲各地的游蛇科蛇类,但人们对其毒腺分泌物的成分和生物活性知之甚少。为了对其进行表征,我们研究了其致水肿、皮肤坏死和肌肉坏死活性。对于致水肿活性,将含有不同量分泌物的溶液皮下注射到小鼠的右足垫中,随后将两只脚切断并分别称重。对于肌肉坏死活性,给小鼠肌肉注射含有40微克分泌物的溶液,并在不同时间间隔取血以测定血清肌酸激酶活性,同时取出腓肠肌进行显微镜检查(苏木精-伊红染色)。对于皮肤坏死活性,将含有不同量分泌物的溶液注射到小鼠剃毛的背部皮肤中;在皮肤内表面测量坏死病变,并修剪后进行显微镜检查(苏木精-伊红染色)。使用动力学方法评估磷脂酶A2活性。结果表明,巴塔哥尼亚菲洛德蛇毒腺分泌物具有高致水肿活性和中度肌肉坏死及皮肤坏死活性,但缺乏磷脂酶A2效应。关于水肿,注射0.26微克毒腺分泌物可使重量增加30%。在显微镜下,注射后12小时肌肉坏死达到最高强度,血清肌酸激酶水平也证明了这一点。皮肤坏死与注射的分泌物量成正比,最小坏死剂量为15.7微克。当分泌物与1 mM Na2EDTA预孵育时,肌肉坏死、致水肿和皮肤坏死活性受到抑制。这表明负责这些活性的酶大多是金属蛋白酶。迄今为止进行的所有研究都证明了巴塔哥尼亚菲洛德蛇(栖息于阿根廷东北部地区)毒腺分泌物的潜在毒性,并且这种游蛇科蛇类造成的局部损伤与具窍蝰蛇咬伤造成的损伤非常相似。后者表明在考虑采用何种医疗治疗时,应对受害者进行更仔细的评估。

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