RESUMO
Objective To investigate the renoprotective effect of aspirin-triggered lipoxins(ATL)on kidney of mice with acute kidney injury(AKI).Methods Eighty-eight male specific pathogen-free(SPF)C57BL/6J mice were randomly divided into lipopolysaccharide(LPS)groups(including 2 h group,4 h group,8 h group,12 h group, 24 h group),ATL+LPS(including 2 h group,4 h group,8 h group,12 h group,24 h group)and normal control group according to random numble table,and each group had 8 mice.The mice in LPS groups were given LPS intraperitoneal injection to establish AKI animal models,while the mice in ATL+LPS groups were given ATL intraperitoneal injection 30 minutes before LPS intraperitoneal injection.The enzyme linked immunosorbent assay was used to test the serum creatinine(Scr),serum urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),cysteine-rich protein-61 (Cyr61)and netrin-1 levels of mice.Results The kidney tissue injury scores of mice of ATL+LPS group[4 h:(22.32 ± 1.04)scores,8 h:(31.11 ± 1.86)scores,12 h:(18.22 ± 0.92)scores,24 h:(20.87 ± 3.18)scores] were lower than those of LPS group at the corresponding time points[4 h:(35.47 ± 2.27)scores,8 h:(52.28 ± 2.82) scores,12 h:(54.99 ± 4.56)scores,24 h:(53.41 ± 4.76)scores],and the differences were statistically significant(all P<0.01).The values of Scr,BUN,TNF-α and IL-1β in ATL+LPS group[Scr 8 h:(143.07 ± 5.02)μmol/L, BUN 12 h:(33.07 ± 3.52)mmol/L,TNF-α 4 h:(196.33 ± 14.181)ng/L and 8 h:(221.77 ± 10.11)ng/L,IL-1β 4 h:(50.25 ± 2.67 ng/L)]were lower than those in LPS group at the corresponding time points[Scr 8 h:(227.43 ± 11.17)μmol/L,BUN 12 h:(59.68 ± 3.84)mmol/L,TNF-α 4 h:(267.87 ± 26.48)ng/L and 8 h:(334.78 ± 21.08)ng/L,IL-1β 4 h:(89.45 ± 5.87)ng/L],and the differences were statistically significant(all P<0.01). The urine NGAL[4 h:(56.76 ± 4.01)μg/L,8 h:(65.44 ± 7.81)μg/L],KIM-1[8 h:(78.19 ± 9.48)μg/L] and netrin-1[8 h:(40.12 ± 2.01)ng/L,12 h:(36.87 ± 2.87)ng/L]of mice in ATL+LPS group were lower than those in LPS group at the corresponding time points[NGAL 4 h:(168.77 ± 10.77)μg/L,8 h:(155.33 ± 8.26) μg/L;KIM-1 8 h:(124.73 ± 13.47)μg/L;netrin-1 8 h:(89.17 ± 2.74)ng/L,12 h:(81.11 ± 3.88)ng/L],and the differences were statistically significant(all P<0.01).Conclusions ATL can treat LPS-induced AKI and play a renoprotective role in the kidney.
RESUMO
La preeclampsia es un síndrome hipertensivo que se presenta a partir de la semana 20 de gestación. El objetivo de este trabajo es describir la producción y los mecanismos de acción de las lipoxinas inducidas por la aspirina y proponerlas como una alternativa adecuada para modular los procesos oxidativos característicos de la preeclampsia y los ciclos proinflamatorios que inician con la cascada de activación del factor nuclear-kappa B, y en consecuencia de sus productos. La preeclampsia se caracteriza por la producción de sustancias proinflamatorias, que inducen la activación de células endoteliales, directa o indirectamente, a través de la activación previa de los monocitos, los cuales pueden generar especies reactivas de oxígeno y expresar moléculas de adhesión que median la interacción con el endotelio, contribuyendo a su estado de disfunción, activación e inducción de la cascada de señalización del factor nuclear-kappa B. La aspirina por su parte, induce la producción de lipoxinas que inhiben la activación del factor nuclear-kappa B mediante el bloqueo de la proteína quinasa IkB, necesaria para desencadenar la activación de la vía canónica y no canónica de este factor nuclear.
Preeclampsia is a hypertensive syndrome that occurs after the 20th weeks of gestation. The objective of this review was to describe the mechanisms of production and action of aspirin- triggered lipoxins in order to consider them as a suitable alternative to modulate oxidative processes, which are characteristic of preeclampsia and proinflammatory cycles starting with cascade activation of nuclear factor-kappa B, consequently of their products. Preeclampsia is characterized by the production of proinflammatory substances that induce directly or indirectly endothelial cell activation,, through prior activation of monocytes, which can generate reactive oxygen species and expression of adhesion molecules that mediate interacting with the endothelium, contributing to its dysfunction, activation and induction of signaling cascade nuclear factor-kappa B. Aspirin induces lipoxin, which inhibits the activation of nuclear factor-kappa B by blocking IkB protein kinase, necessary to trigger the activation of canonical and non-canonical pathway of this nuclear factor.