Chies Agnaldo Bruno, Nakazato Paula Carolina Grande, Spadella Maria Angélica, Zorzi Patrícia, Gomes Maria Cecília Jordani, D'Albuquerque Luiz Augusto Carneiro, Castro-E-Silva Orlando
PhD, Laboratory of Pharmacology, Marilia Medical School, Marilia-SP, Brazil. Conception and design of the study, analysis and interpretation of data, statistical analysis, manuscript writing.
Graduate student, Marilia Medical School, Marilia-SP, Brazil. Conception and design of the study, technical procedures, acquisition of data.
Acta Cir Bras. 2018 Sep;33(9):775-784. doi: 10.1590/s0102-865020180090000005.
To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver.
SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations.
I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments.
Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.
评估用卡巴拉汀预处理是否能够减轻大鼠肝脏缺血/再灌注（I/R）诱导的损伤。
使用假手术动物或接受I/R的动物，这些动物在缺血前50分钟或15分钟未接受治疗或用卡巴拉汀（2mg/kg）进行预处理。在I/R方案后，处死这些动物并收获其肝脏，以测量线粒体肿胀以及丙二醛（MDA）、亚硝酸盐和硝酸盐组织浓度。还采集血液用于测定血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）。
I/R促使研究动物的线粒体肿胀显著增加。这种线粒体肿胀的增加被卡巴拉汀部分阻止，但仅在缺血前50分钟给药时有效。无论是否进行卡巴拉汀治疗后，均未观察到I/R导致的MDA、亚硝酸盐或硝酸盐组织浓度有显著变化。此外，I/R使AST和ALT均升高。不同的卡巴拉汀治疗并未逆转这些血清酶的升高。
在缺血前50分钟给予卡巴拉汀可减轻I/R诱导所致的线粒体肿胀，这表明肝脏受到损伤。这种保护作用可能与未代谢的乙酰胆碱对库普弗细胞中存在的α7烟碱型乙酰胆碱受体（α7nAChR）的更大刺激有关，从而导致I/R诱导的炎症减轻。
