Роль NF-κB-опосередкованої дії NO-синтаз у дезорганізації сполучної тканини пародонта за умов експериментального метаболічного синдрому

Abstract

В эксперименте на 40 белых крысах исследована роль NF-κB в механизмах дезорганизации соединительной ткани пародонта, зависимых от функционального состояния NO - синтазы (NOS), в условиях моделирования метаболического синдрома (МС). Выявлено, что способность нейрональной NOS ограничивать дезорганизацию соединительной ткани пародонта (коллагенолиз и деполимеризацию протеогликанов), в условиях МС, является NF-κB-опосредованной. Показано, что действие селективного ингибитора индуцибельной NOS аминогуанидина в этих условиях не приводит к NF-κB-зависимым изменениям состояния коллагеновых и неколлагеновых белков в тканях пародонта. Введение ингибитора NF-κB JSH-23 сопровождается повышением коллагенопротективного действия L-аргинина в мягких и костной тканях пародонта.

NO- dependent disorders is an important part of the pathogenesis of metabolic syndrome (MS). It is known that a large number of effects produced by NO are mediated via the activation of nuclear factor κB (NF-κB). Excessive NO formation is accompanied by increased proteolysis and disorganization of connective tissue. The aim of this study was to clarify the role of NF-κB in the mechanisms of disruption of periodontal connective tissue in rats depending on the functional state of NO-synthases (NOS) under modeled MS. Methods. The research was carried out on 40 Wistar male rats weighing 180-230g in 8 series of experiments: during the first series necessary parameters of intact animals (control series) were studied; during the second series we investigated necessary parameters after the MS simulation, the during the third, fourth and fifth series when MS was modeling the animals were administered selective inhibitor of neuronal NO-synthase (nNOS) 7- nitroindazol (7-NI, 30 mg/kg), a selective inhibitor of inducible NO-synthase (iNOS) - aminoguanidine (20 mg/kg) and NO-synthase substrate - L-arginine (500 mg/kg). During the sixth, seventh and eighth series against the background of modeled MS in addition to the above mentioned substances the rats were administered an inhibitor of NF- κB activation II - JSH-23 (4-methyl-N-(3-phenylpropyl) benzene -1,2-diamine, 1 mg/kg). All compounds were administered intraperitoneally twice a week for a period of MS modeling. The state of collagen was assessed by the content of free oxyproline (FO) in the soft tissues and bone tissues. The level of proteoglycans was assessed by their monomers – glycosaminoglycans (GAG). Results. MS modeling is accompanied by increased FO concentration in bone and soft tissues by 61.8 % (p <0.001) and 68.3 % (p <0.001) respectively, increased GAG by 64.3 % (p <0,001) and 80.9 % (p <0.001). The introduction of 7-NI increases FO concentration in soft and bone periodontal tissues of the rats by 23.8 % (p<0.001) and by 21.8 % (p<0.001), GAG by 19.6 % (p<0,001) and 10.6 % (p<0.01) compared with the data of the second series. Under the combined effect produced by 7-NI and JSH-23 FO concentration and GAG decreases in periodontal soft tissues by 20.5 % (p<0.01) and 20.8 % (p<0.01), in periodontal bone tissue by 24.5 % (p<0.001) and by 16.0 % (p<0.01) compared to the results of the third series. The introduction of aminoguanidine limits FO content in soft and bone periodontal tissue by 40.0 % (p <0.001) and 43.4 % (p<0.001), GAG by 36.5 % (p<0.001) and 34.1 % (p<0.001) compared with the data of the second series. Under the combined effect produced by aminoguanidine and JSH-23 the concentration of GAG and FO in periodontal tissues is remaining reduced.The introduction of L-arginine under conditions of MS decreases FO concentration in soft and bone periodontal tissue by 32.8 % (p<0.001) and 30.8 % (p<0.001), GAG by 27.0 % (p<0.001) and 32.4 % (p<0.001) compared with the data of the second series. Under the combined effect produced by L-arginine and JSH-23 in the conditions of modeled MS FO concentration was significantly reduced in periodontal soft tissues by 25.1 % (p<0.01), the periodontal tissue by 21.6 % (p<0.01) compared with the data of the fifth series. GAG content did not change significantly. Conclusions: 1) The ability of nNOS to limit the disruption of periodontal connective tissue (collagenolysis and proteoglycan depolymerization) in modeled MS is NF-κB- mediated. 2) Effect of selective iNOS inhibitor aminoguanidine in modeled MS is not accompanied by NF-κB- dependent changes in the state of the collagen and noncollagen fibers in the periodontal tissues. 3) Introduction of an inhibitor NF-κB JSH-23 under MS is accompanied by increased collagen-protecting action of L-arginine in soft and bone tissues of periodontium.