乌头赤石脂丸方对急性心肌梗死后应用阿司匹林致胃黏膜损伤大鼠前列腺素E2和信号通路的影响  

Effects of Wutou Chishizhi Pills on Prostaglandin E2 and Signaling Pathways in Rats with Gastric Mucosal Injury Induced by Aspirin after Acute Myocardial Infarction

作　　者：史晓梅 肖钰雪 王鑫赫 谢璐璐 王松 连春雨 郭军鹏[1] 刘宏岩[1] SHI Xiao-mei;XIAO Yu-xue;WANG Xin-he;XIE Lu-lu;WANG Song;LIAN Chun-yu;GUO Jun-peng;LIUHong-yan(Changchun University of Chinese Medicine,Changchun Jilin 130117)

机构地区：[1]长春中医药大学,吉林长春130117

出　　处：《世界中西医结合杂志》2023年第3期510-515,共6页World Journal of Integrated Traditional and Western Medicine

基　　金：吉林省科技厅科技发展计划项目(20170101007JC)。

摘　　要：目的 探讨乌头赤石脂丸方对急性心肌梗死后应用阿司匹林致胃黏膜损伤大鼠的前列腺素E2(Prostaglandin E2,PGE2)和Nrf2/HO-1/NQO-1及Beclin1/LC3信号通路的影响。方法 将40只SPF级雄性大鼠随机分为正常组、模型组、奥美拉唑组和乌头赤石脂丸组4组。除正常组外,其他3组大鼠均结扎心脏左冠状动脉前降支,再灌胃0.2 g/kg的阿司匹林4 d复制急性心梗(AMI)后胃损伤模型,治疗组同时给予相应药物治疗7 d。观察大鼠胃黏膜损伤程度;苏木素-伊红(HE)染色法观察胃组织的形态学变化;ELISA法检测血清中PGE2、血管内皮生长因子(Vascular Endothelial Growth Factor, VEGF)含量及血浆中凝血指标[凝血酶原时间(Prothrombin Time, PT),凝血酶时间(ThrombinTime, TT),纤维蛋白原(Fibrinogen, FIB)];Western blot法检测胃组织[核转录因子E2相关因子2(Nuclear transcription factor E2related factor 2,Nrf2),血红素氧合酶-1(Heme oxygenase-1,HO-1),醌氧化还原酶-1(Quinone oxidoreductase-1,NQO-1)及自噬相关蛋白(Beclin-1,Beclin-1)、微管相关蛋白1轻链3(Microtubule-associated protein 1 light chain 3,LC3)]。结果 与模型组比较,乌头赤石脂丸组的胃黏膜损伤指数降低(P<0.01),黏膜结构相对完整,未见黏膜脱落等病理变化,炎性细胞浸润少见。乌头赤石脂丸组PGE2、VEGF含量明显增高(P<0.01)。乌头赤石脂丸组的PT、TT均明显缩短(P<0.01),FIB含量明显降低(P<0.01)。乌头赤石脂丸组大鼠胃组织Nrf2、HO-1及NQO-1表达明显增高(P<0.01),Beclin1和LC3表达明显降低(P<0.01)。结论 乌头赤石脂丸方能够减轻心梗后应用阿司匹林导致的胃粘膜损伤,其作用机制可能与促进PGE2的释放,激活Nrf2/HO-1/NQO-1和Beclin1/LC3信号通路有关。Objective To investigate the effects of Wutou Chishizhi Pills(WCP)on prostaglandin E2(PGE2)and the Nrf2/HO-1/NQO-1 and Beclin1/LC3 signaling pathways in rats with gastric mucosal injury induced by aspirin after acute myocardial infarction(AMI).Methods SPF rats were randomly assigned into 4 groups:a normal group,a model group,an omeprazole group,and a WCP group.Except for the normal group,the other groups were subjected to ligation of the left anterior descending coronary artery,and then received 0.2 g·kg-1 aspirin by gavage for 4 days to replicate the gastric injury model after AMI.Corresponding drugs were administrated for 7 days.The injury of gastric mucosa was evaluated,and hematoxylin-eosin(HE)staining was employed to observe the morphological changes of the gastric tissue.The serum levels of PGE2 and vascular endothelial growth factor(VEGF)and the plasma levels of coagulation indexes[prothrombin time(PT),thrombin time(TT),and fibrinogen(FIB)]were determined by enzyme-linked immunosorbent assay(ELISA).The expression levels of nuclear transcription factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),quinone oxidoreductase-1(NQO-1),Beclin-1,and microtubule-associated protein 1 light chain 3(LC3)in the gastric tissue were determined by Western blotting.Results Compared with the model group,the WCP group showed decreased gastric mucosal injury index(P <0.01),intact mucosal structure,no pathological changes such as sloughing of mucosa,andmild inflammatory infiltration.The WCP group had higher levels of PGE2 and VEGF(P <0.01),shorter PT and TT(P <0.01),and lower level of FIB(P <0.01)than the model group.Compared with the model group,WCP up - regulated theprotein levels of Nrf2,HO -1,and NQO -1(P <0.01)and down - regulated the protein levels of Beclin1 and LC3(P <0.01).Conclusion WCP can reduce the gastric mucosal injury caused by aspirin after AMI by promoting the release ofPGE2 and activating the Nrf2/ HO -1/ NQO -1 and Beclin1/ LC3 signaling pathways.

关 键 词：乌头赤石脂丸 胃黏膜损伤 出血 急性心肌梗死 氧化应激 自噬 

分 类 号：R285.5[医药卫生—中药学]