Licks Francielli, Minuzzo Hartmann Renata, Schemitt Elizângela, Raskopf Colares Josieli, Marques Camila, Fillmann Henrique, Possa Marroni Norma
Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Program in Medicine: Medical Sciences, UFRGS; Porto Alegre, RS, Brazil.
Hepatol Forum. 2022 Apr 26;3(2):51-56. doi: 10.14744/hf.2021.2021.0034. eCollection 2022 May.
Portal hypertension (PH) is a syndrome associated with cirrhosis and characterized by a progressive increase in portal pressure, with consequent compensatory vascular dilation. Gastric vascular changes associated with oxidative and nitrosative stress characterize the clinical presentation of portal hypertensive gastropathy (PHG). In addition, the inflammatory process is considered an aggravating factor for severity by contributing to gastric tissue injury. The aim of this study was to investigate the synergistic anti-inflammatory and antioxidant action of N-acetylcysteine (NAC) in the stomach of rats with PH.
Eighteen Wistar male rats were used in this experimental protocol and were divided into three groups with six in each group: sham-operated (SO), partial portal vein ligation (PPVL), and PPVL + NAC. Treatment with NAC at a dose of 10 mg/kg (i.p.) was initiated on day 8 after surgery and continued for 7 days. We evaluated the expression of iNOS, NQO-1, HSP-90, and SOD by Western blot, as well as nuclear factor-kappa B (NF-κB) and tumor necrosis factor (TNF)-α staining by immunohistochemistry, in the rat stomach.
The PPVL group exhibited increased expression of HSP-90, iNOS, SOD, and NQO-1 when compared with controls. NAC reduced the expression of all studied proteins. Similarly, NF-κB and TNF-α staining was increased in PPVL animals versus controls and reduced in PPVL + NAC versus PPVL animals, respectively.
These results suggest the effectiveness of NAC as a dual anti-inflammatory and antioxidant in animals with experimental PHG induced by partial ligation of the portal vein.
门静脉高压(PH)是一种与肝硬化相关的综合征,其特征是门静脉压力逐渐升高,随之出现代偿性血管扩张。与氧化应激和亚硝化应激相关的胃血管变化是门静脉高压性胃病(PHG)临床表现的特征。此外,炎症过程通过导致胃组织损伤被认为是病情严重程度的加重因素。本研究的目的是探讨N-乙酰半胱氨酸(NAC)在门静脉高压大鼠胃中的协同抗炎和抗氧化作用。
本实验方案使用了18只雄性Wistar大鼠,分为三组,每组6只:假手术组(SO)、部分门静脉结扎组(PPVL)和PPVL + NAC组。术后第8天开始腹腔注射剂量为10 mg/kg的NAC进行治疗,并持续7天。我们通过蛋白质印迹法评估大鼠胃中诱导型一氧化氮合酶(iNOS)、醌氧化还原酶1(NQO-1)、热休克蛋白90(HSP-90)和超氧化物歧化酶(SOD)的表达,以及通过免疫组织化学评估核因子κB(NF-κB)和肿瘤坏死因子(TNF)-α染色。
与对照组相比,PPVL组HSP-90、iNOS、SOD和NQO-1的表达增加。NAC降低了所有研究蛋白的表达。同样,与对照组相比,PPVL组动物的NF-κB和TNF-α染色增加;与PPVL组动物相比,PPVL + NAC组的NF-κB和TNF-α染色减少。
这些结果表明NAC作为一种双重抗炎和抗氧化剂对由门静脉部分结扎诱导的实验性PHG动物有效。