Jin Hongzhong, Yang Xiaojia, Zhao Kailiang, Zhao Liang, Chen Chen, Yu Jia
PhD, Department of Hepatobiliary Surgery, Renmin Hospital, Wuhan University, Hubei Province, China. Acquisiton and analysis of data, manuscript writing.
MD, PhD, Department of Hepatobiliary Surgery, Renmin Hospital, Wuhan University, Hubei Province, China. Conception and design of the study, supervised all phases of the study, final approval.
Acta Cir Bras. 2019 Aug 19;34(6):e201900609. doi: 10.1590/s0102-865020190060000009.
The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats.
Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot.
The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups.
Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.
本研究旨在阐明糖原合成酶激酶-3β（GSK-3β）抑制剂对大鼠急性坏死性胰腺炎（ANP）所致急性肺损伤进展的疗效及其潜在机制。
将72只大鼠随机分为6组：（1）ANP-溶剂对照组；（2）ANP-TDZD-8组；（3）ANP-SB216763组；（4）假手术-溶剂对照组；（5）假手术-TDZD-8组；（6）假手术-SB216763组。对大鼠胰腺和肺组织进行血液生化检测、组织病理学检查及免疫组化分析。采用蛋白质免疫印迹法检测肺组织中GSK-3β、磷酸化GSK-3β（Ser9）、诱导型一氧化氮合酶（iNOS）、细胞间黏附分子-1（ICAM-1）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）的蛋白表达。
结果显示，GSK-3β抑制剂干预可减轻胰腺和肺的病理损伤（P<0.01），降低血清淀粉酶、脂肪酶、胸腔积液及肺湿干比，降低血清白细胞介素-1β和白细胞介素-6浓度（P<0.01），抑制核因子-κB（NF-κB）激活，减少iNOS、ICAM-1和TNF-α蛋白表达，但上调ANP大鼠肺组织中IL-10表达（P<0.01）。ANP-TDZD-8组的炎症反应及各项指标低于ANP-SB216763组。
抑制GSK-3β通过NF-κB信号通路的抑制作用减轻与ANP相关的急性肺损伤。不同种类的GSK-3β抑制剂对ANP急性肺损伤的作用不同。
