Demirbilek S, Sizanli E, Karadag N, Karaman A, Bayraktar N, Turkmen E, Ersoy M O
Department of Anesthesiology and Reanimation, Medical School of Inonu University, Malatya, Turkey.
Eur Surg Res. 2006;38(1):35-41. doi: 10.1159/000091525. Epub 2006 Feb 14.
We aimed to investigate the effects of methylene blue (MB) on NO production, myeloperoxidase (MPO) activity, antioxidant status and lipid peroxidation in lung injury during different stages of sepsis in rats.
Rats were randomly divided into 4 groups (n = 20): group C, sham operated; group CMB, sham operated and receiving MB (25 mg/kg, i.p.); group S, sepsis; group SMB, sepsis and receiving MB (25 mg/kg, i.p.). Sepsis was induced by cecal ligation and puncture (CLP). The MB dose was administered after CLP. Each group was subdivided into two subgroups (n = 10) which were sacrificed at 9 or 18 h after the surgical procedure. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and MPO activity, total nitrite/nitrate and malondialdehyde (MDA) in the lung tissue were measured. Lung injury was graded from 1 (injury to 25% of the field) to 4 (diffuse injury) by the pathologist.
In group SMB, while SOD and CAT increased in both early and late sepsis periods, GSH-PX increased significantly only in the early sepsis period when compared with group S. Increase in lung MPO activity after CLP-induced sepsis was prevented by MB administration. MB significantly decreased to nitrite/nitrate and MDA levels both in early and late sepsis periods when compared with group S (p < 0.05). Group S showed a marked increase in neutrophil infiltration into the interstitial space and thickening of the alveolar septa, whereas the alveolar damage score was lower in the SMB group (p < 0.05).
MB reduced the MPO activity and lipid peroxidation by both decreasing oxidative stress and NO overproduction in the lungs, which resulted in the attenuation of lung injury after CLP-induced sepsis in rats.
我们旨在研究亚甲蓝(MB)对大鼠脓毒症不同阶段肺损伤中一氧化氮(NO)生成、髓过氧化物酶(MPO)活性、抗氧化状态及脂质过氧化的影响。
将大鼠随机分为4组(n = 20):C组,假手术组;CMB组,假手术且接受MB(25 mg/kg,腹腔注射);S组,脓毒症组;SMB组,脓毒症且接受MB(25 mg/kg,腹腔注射)。通过盲肠结扎和穿刺(CLP)诱导脓毒症。CLP后给予MB剂量。每组再分为两个亚组(n = 10),在手术操作后9或18小时处死。检测肺组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-PX)水平及MPO活性、总亚硝酸盐/硝酸盐和丙二醛(MDA)。病理学家将肺损伤从1级(损伤面积达视野的25%)分级至4级(弥漫性损伤)。
在SMB组中,与S组相比,早期和晚期脓毒症阶段SOD和CAT均升高,而GSH-PX仅在早期脓毒症阶段显著升高。MB给药可防止CLP诱导脓毒症后肺MPO活性增加。与S组相比,MB在早期和晚期脓毒症阶段均显著降低亚硝酸盐/硝酸盐和MDA水平(p < 0.05)。S组显示中性粒细胞浸润至间质间隙显著增加且肺泡间隔增厚,而SMB组的肺泡损伤评分较低(p < 0.05)。
MB通过降低肺内氧化应激和NO过量生成,降低了MPO活性和脂质过氧化,从而减轻了CLP诱导的大鼠脓毒症后的肺损伤。