Araujo e Silva Ana Candida, de Oliveira Lemos Fernanda, Gomes Marco Túlio Ribeiro, Salas Carlos Edmundo, Lopes Miriam Teresa Paz
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
J Pharm Pharmacol. 2015 Jan;67(1):133-41. doi: 10.1111/jphp.12318. Epub 2014 Sep 11.
The aim of this study was to extend our knowledge about the mechanism involved in the gastroprotective effect of P1G10, a proteolytic fraction rich in cysteine proteinases from Vasconcellea cundinamarcensis (syn. Carica candamarcensis) latex, which demonstrated gastric healing and protection activities in rats.
Wistar rats were submitted to gastric lesions by indomethacin and treated with P1G10 (10 mg/kg). Free thiol groups and prostaglandin E2 content were measured in gastric mucosal and gastrin levels in blood samples. To evaluate the participation of nitric oxide (NO) or proteolytic activity of P1G10 on its gastroprotective effect, animals were treated with an inhibitor of NO production (L-NAME) or the fraction inhibited by iodoacetamide, respectively. Gastric secretion study (acidity and pepsin activity) was also performed.
P1G10 (10 mg/kg) inhibited the occurrence of gastric lesions by indomethacin, restored the free thiol groups content on gastric mucosa and increased moderately prostaglandin E2 levels (34%). Furthermore, the treatment decreased the gastrin levels (95%), suggesting a possible modulation of secretory activity. This effect was accordant with attenuation of gastric acidity (42%) and pepsin activity (69%) seen in animals subjected to pyloric ligation. The inhibition of NO production or the proteolytic activity of P1G10 does not affect the gastroprotective effect.
These results can explain the gastroprotective activity of P1G10 and serve a basis for further studies of this active principle.
本研究旨在拓展我们对P1G10胃保护作用机制的认识。P1G10是一种富含半胱氨酸蛋白酶的蛋白水解组分，来源于昆迪纳马卡番木瓜（同义词：坎达马卡番木瓜）乳胶，已在大鼠中证明具有胃愈合和保护活性。
将Wistar大鼠用吲哚美辛造成胃损伤，并用P1G10（10 mg/kg）进行治疗。测定胃黏膜中的游离巯基基团和前列腺素E2含量以及血样中的胃泌素水平。为了评估一氧化氮（NO）或P1G10的蛋白水解活性对其胃保护作用的参与情况，分别用NO生成抑制剂（L-NAME）或碘乙酰胺抑制的组分对动物进行治疗。还进行了胃分泌研究（酸度和胃蛋白酶活性）。
P1G10（10 mg/kg）抑制了吲哚美辛引起的胃损伤的发生，恢复了胃黏膜中游离巯基基团的含量，并适度提高了前列腺素E2水平（34%）。此外，该治疗降低了胃泌素水平（95%），提示可能对分泌活性有调节作用。这种作用与幽门结扎动物中观察到的胃酸度降低（42%）和胃蛋白酶活性降低（69%）一致。抑制NO生成或P1G10的蛋白水解活性并不影响胃保护作用。
这些结果可以解释P1G10的胃保护活性，并为进一步研究这一活性成分提供基础。
