摘要
[目的]观察苦杏仁苷对肺心病大鼠呼吸衰竭的改善作用及对表皮生长因子受体(epidermal growth factor receptor,EGFR)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路的影响。[方法]取50只无特定病原体(specific pathogen free,SPF)级雄性SD大鼠,随机分为正常对照组(常氧+腹腔注射0.9%氯化钠注射液)、模型组(低氧+腹腔注射0.9%氯化钠注射液)、苦杏仁苷低剂量组(低氧+腹腔注射10mg·kg-1苦杏仁苷)、苦杏仁苷高剂量组(低氧+腹腔注射20mg·kg-1苦杏仁苷)和阳性对照组(低氧+腹腔注射1.0mg·kg-1盐酸纳洛酮),每组各10只,药物处理均为1次/d,每周6d。干预4周后,检测肺功能、动脉血气相关指标、血流动力学和右心指数,以酶联免疫吸附(enzyme-linked immunosorbent assay,ELISA)法检测血清白细胞介素-8(interleukin-8,IL-8)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平,以苏木精-伊红(hematoxylin-eosin,HE)染色观察肺组织病理学变化,Western blot检测肺组织EGFR、磷酸化EGFR(phosphorylation-EGFR,p-EGFR)、p38MAPK、磷酸化p38MAPK(phosphorylation-p38 MAPK,p-p38MAPK)蛋白表达情况。[结果]苦杏仁苷低、高剂量组和阳性对照组较模型组呼吸频率、呼气峰流速值(peak expiratory flow,PEF)、50%肺活量时最大呼气流量(50%forced expiratory flow,FEF50)、氢离子浓度(potential of hydrogen,pH)、氧分压(partial pressure of oxygen,PaO2)水平升高,呼气阻力、二氧化碳分压(partial pressure of carbon dioxide,PaCO2)、血清IL-8、TNF-α水平、平均肺动脉压(mean pulmonary artery pressure,mPAP)、右心指数、p-EGFR、p-p38MAPK蛋白表达降低(P<0.05)。与阳性对照组比较,苦杏仁苷高剂量组上述指标差异无统计学意义(P>0.05)。[结论]苦杏仁苷对肺心病大鼠呼吸衰竭具有抑制作用,其作用机制可能与抑制EGFR/MAPK信号通路相关蛋白表达水平有关。
[Objective]To observe the ameliorating effect of amygdalin on respiratory failure in corpulmonale rats and its effect on the epidermal growth factor receptor(EGFR)/mitogen-activated protein kinase(MAPK)signaling pathway.[Methods]Fifty specific pathogen free(SPF)male SD rats were randomly divided into normal control group(normal oxygen+intraperitoneal injection of 0.9%sodium chloride injection),model group(hypoxia+intraperitoneal injection of 0.9%sodium chloride injection),amygdalin low-dose group(hypoxia+intraperitoneal injection of 10mg·kg-1 amygdalin),amygdalin high-dose group(hypoxia+intraperitoneal injection of 20mg·kg-1 amygdalin)and positive control group(hypoxia+intraperitoneal injection of 1.0mg·kg-1 naloxone hydrochloride),with 10 rats in each group,treated once a day,every six days one week.After 4 weeks of intervention,the lung function related indexes,arterial blood gas related indexes,hemodynamics and right heart index were tested,enzyme-linked immunosorbent assay(ELISA)method was used to detect serum levels of interleukin-8(IL-8),tumor necrosis factor-α(TNF-α).Pathological changes in lung tissue was observed with hematoxylineosin(HE)staining,and EGFR,phosphorylation-EGFR(p-EGFR),p38MAPK,phosphorylation-p38MAPK(p-p38MAPK)protein expressions in lung tissue were detected with Western blot.[Results]Compared with model group,breath rates,peak expiratory flow(PEF),and 50%forced expiratory flow(FEF50),potential of hydrogen(pH),partial pressure of oxygen(PaO2)increased,while expiratory resistance,partial pressure of carbon dioxide(PaCO2),serum levels of IL-8 and TNF-α,mean pulmonary artery pressure(mPAP),right heart index,p-EGFR、p-p38MAPK protein expression decreased in amygdalin low-dose group,amygdalin high-dose and positive control group(P<0.05).There was no significant difference in the above indicators between high-dose amygdalin group and positive control group(P>0.05).[Conclusion]Amygdalin has an inhibitory effect on respiratory failure in rats with corpulmonale,probably by inhibiting the expression levels of EGFR/MAPK signaling pathway related proteins.
作者
汪洋
张辉
马东波
伍冬冬
邓翔
李芳
吴秋歌
郭胜存
WANG Yang;ZHANG Hui;MA Dongbo(The First Affiliated Hospital of Zhengzhou University,Zhengzhou(450000),China)
出处
《浙江中医药大学学报》
CAS
2021年第4期384-390,共7页
Journal of Zhejiang Chinese Medical University
基金
国家自然科学基金项目(81701695)。
关键词
肺心病
肺动脉高压
呼吸衰竭
通气障碍
苦杏仁苷
表皮生长因子受体
丝裂原活化蛋白激酶
信号通路
corpulmonale
pulmonary hypertension
respiratory failure
ventilatory disorders
amygdalin
epidermal growth factor receptor
mitogen-activated protein kinase
signaling pathway
