摘要
【目的】探讨橘皮苷通过调控磷脂酰肌醇-3激酶(phosphatidylinositol-3 kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/核转录因子-κB(nuclear transcription factor-κB,NF-κB)信号通路对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠相关性肺损伤的减轻作用。【方法】取75只大鼠,其中60只建立大鼠SAP模型,然后分为橘皮苷低、中、高剂量(A、B、C)组和模型(M)组;另15只为假手术(S)组。手术后3 h,A、B、C组股静脉注射10、20、40 mg/kg橘皮苷,M、S组同法注射等体积生理盐水。统计24 h生存率,检测血浆淀粉酶(amylase,AMS)水平变化;检测各组肺泡灌洗液(broncho-alveolar lavage fluid,BALF)中IL-6、IL-1β、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;观察肺组织病理学改变;检测各组肺组织中PI3K、NF-κB p65mRNA和蛋白表达及Akt1/2 mRNA、pAkt1/2/Akt1/2。【结果】模型组存活大鼠精神萎靡、反应迟钝、喜卧、呼吸急促、浅快,橘皮苷3个剂量组均有所改善;M组24 h存活率低于S组,B、C组均高于M组(P<0.05)。存活大鼠血浆AMS水平干预前M组、A组、B组、C组均高于S组(P<0.05),干预后12、24 h组间比较,M组均高于S组(P<0.05),且橘皮苷的作用均呈剂量依赖性,本组内比较M、A、B和C组均逐渐降低;病理学观察发现,S组肺组织结构无异常,M组肺间质、肺泡间隔、肺泡等均出现明显病理改变;A、B、C均有所改善。BALF中IL-6、IL-1β、TNF-α水平、肺组织中PI3K、NF-κB p65 mRNA和蛋白相对表达量、Akt1/2mRNA相对表达量、pAkt1/2/Akt1/2组间比较,M组均高于S组(P<0.05),且橘皮苷的作用均呈剂量依赖性。【结论】橘皮苷可通过调控PI3K/Akt/NF-κB信号通路减轻SAP大鼠相关性肺损伤,抑制气道炎症状态,其中40 mg/kg的橘皮苷干预效果最佳。
【Objective】To explore the effect of hesperidin on the reduction of related lung injury in rats with severe acute pancreatitis(SAP) by regulating phosphatidylinositol-3 kinase(PI3 K)/protein kinase B(Akt)/nuclear transcription factor-κB(NF-κB) signaling pathway.【Methods】A total of 75 rats were selected, and 60 of them were used to establish SPA models. Then they were divided into groups in low, medium and high doses of hesperidin(A, B, C) and model group(M), and the remaining 15 rats were noted as sham operation group(S). After 3 hours of operation, in the groups A, B and C, 10, 20 and 40 mg/kg hesperidin was injected via femoral vein,and in the groups M and S, the same volume of saline was injected. The 24-hour survival rates were counted and the changes of plasma amylase(AMS) were compared. The levels of interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in broncho-alveolar lavage fluid(BALF) were measured. The pathological changes of lung tissue were observed. The expression of PI3 K, NF-κB p65, Akt1/2 and pAkt1/2/Akt1/2 in lung tissues were detected. 【Results】 In the model group, the surviving rats were mentally depressed, unresponsive, sleepy, and their breath was shallow and fast, while it was improved in the A, B and C groups. The 24-hour survival rate in the group M was lower than that in the group S, and those in the group B and C were higher than that in the group M(P< 0.05). The plasma AMS levels in the M group, A group, B group and C group were higher than that in the S group before intervention(P< 0.05). Compared with group S after 12 and 24 hours of intervention, the effect of hesperidin in group M was higher(P< 0.05), and the effect of hesperidin was dose-dependent. Compared with groups, it lower gradually in groups M, A, B and C. Pathological observation showed that there was no abnormality of lung tissue structure in group S, and there were obvious pathological changes in pulmonary interstitium, alveolar septum and alveoli in group M. Those were all improved in groups A, B and C. The levels of IL-6, IL-1β and TNF-α in BALF, mRNA and protein expression of PI3 K and NF-κB p65 in lung tissue, relative expression of Akt1/2 mRNA and pAkt1/2/Akt1/2 in the M group were higher than those in the S group(P<0.05), and the effect of hesperidin was dose-dependent.【Conclusion】Hesperidin can alleviate the related lung injury and inhibit the airway inflammation in SAP rats by regulating PI3 K/Akt/NF-κB signaling pathway. Hesperidin(40 mg/kg) is of the best intervention effect.
作者
胡涛
冯强
王媛媛
尹德宏
徐文漭
HU Tao;FENG Qiang;WANG Yuan-yuan;YIN De-hong;XU Wen-mang(Department of Critical Medicine,the 920th Hospital of the Joint Service Support Force of PLA,Kunming 650032,China)
出处
《武警后勤学院学报（医学版）》
CAS
2019年第9期13-18,共6页
Journal of Logistics University of PAP（Medical Sciences）
