摘要
目的基于神经生长因子(NGF)/酪氨酸激酶受体A(TrkA)通路探讨天麻素注射液治疗局灶性脑缺血致肺损伤大鼠的作用机制。方法将40只SD大鼠随机分为4组:正常组、假手术组、模型组和天麻素治疗组(10只/组)。采用栓塞大鼠右侧大脑中动脉复制局灶性脑缺血模型,造模成功后,用天麻素注射液腹腔注射10 mg/kg,1次/d,持续14 d;假手术组和模型组大鼠不予治疗。治疗结束后,测定大鼠肺组织湿/干重比值,HE染色检测肺组织病理变化,ELISA法检测动脉血液中炎性因子(IL-10、TNF-α)的含量,Western blot检测肺组织NF-κB p65、TNF-α的表达,免疫组织化学染色法及蛋白质免疫印迹试验检测肺组织NGF、TrkA的表达。结果与正常组和假手术组相比,模型组呈现出明显的炎症性肺损伤病理表型,肺湿/干重比值增加(P<0.01),动脉血中TNF-α浓度增高(P<0.01),肺组织内NF-κB p65(P<0.01)、TNF-α(P<0.01)、NGF(P<0.05)和TrkA(P<0.05)蛋白表达水平上升;与模型组相比,天麻素治疗组肺部炎性病理变化减轻,肺湿/干重比值降低(P<0.05),动脉血中TNF-α浓度降低(P<0.01),IL-10浓度增高(P<0.01),肺组织内NF-κB p65和TNF-α蛋白表达水平降低(P<0.05),肺组织内NGF和TrkA蛋白表达水平增加(P<0.05)。结论脑缺血可引起炎症性肺损伤,NGF/TrkA通路可能参与了炎症反应的发生过程;天麻素注射液可减轻脑缺血大鼠的肺损伤,其机制可能与NGF/TrkA通路激活抗炎途径有关。
Objective To investigate the therapeutic mechanism of gastrodin injection for alleviating lung injury caused by focal cerebral ischemia in rats and the role of the NGF-TrkA pathway in mediating this effect.Methods Forty SD rats were equally randomized into normal group,sham-operated group,model group and gastrodin group,and in the latter two groups,rat models of focal cerebral ischemia were established by embolization of the right middle cerebral artery.After successful modeling,the rats were treated with intraperitoneal injection of gastrodin injection at the daily dose of 10 mg/kg for 14 days.After the treatment,the wet/dry weight ratio of the lung tissue was determined,the pathological changes in the lung tissue were observed using HE staining,and the levels of IL-10 and TNF-αin the arterial blood were detected with ELISA.The expressions of NF-κB p65 and TNF-αin the lung tissue were detected with Western blotting,and the expressions of NGF and TrkA were detected using immunohistochemical staining and Western blotting.Results Compared with the normal control and sham-operated groups,the rats in the model group showed obvious inflammatory lung injury,significantly increased wet/dry weight ratio of the lungs(P<0.01),increased TNF-αlevel in arterial blood(P<0.01),and significantly up-regulated protein expressions of NF-κB p65(P<0.01),TNF-α(P<0.01),NGF(P<0.05)and TrkA(P<0.05)in the lung tissue.Treatment with gastrodin injection obviously alleviated lung inflammation,decreased the wet/dry weight ratio of the lungs(P<0.05),and significantly lowered TNF-αlevel(P<0.01)and increased IL-10 level in the arterial blood in the rat models(P<0.01);gastrodin injection also significantly decreased the protein expressions of NF-κB p65 and TNF-α(P<0.05)and up-regulated the expressions of NGF and TrkA in the lung tissue of the rats(P<0.05).Conclusion The NGF/TrkA pathway may participate in cerebral ischemia-induced inflammatory lung injury,which can be obviously alleviated by gastrodin through the activation of the anti-i
作者
产翠翠
马同军
王继胜
张雨微
龚鑫
CHAN Cuicui;MA Tongjun;WANG Jisheng;ZHANG Yuwei;GONG Xin(Department of Anatomy,Wannan Medical College,Wuhu 241002,China)
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2022年第1期116-122,共7页
Journal of Southern Medical University
基金
皖南医学院2020年度中青年科研基金(WK202027)。
