Experimental Study On The Aconitum Chishizhi Pill Prescription On Gastric Injury In Rats Induced By Aspirin After Acute Myocardial Infarction

Objective:To observe the effects of Aconitum Chishi Zhi prescription（ACP）on the injury degree of gastric mucosa,plasma coagulation-fibrinolysis system,oxidative stress of gastric tissue and protein expression of autophagy signal pathway in rats induced by aspirin after acute myocardial infarction,To investigate the protective effect and mechanism of ACP prescription on gastric mucosal injury induced by aspirin in rats after acute myocardial infarction,in order to provide theoretical basis for clinical application.Methods:Forty SPF male rats were randomly divided into normal group,model group,omeprazole（OME）group and ACP group.The model of gastric injury induced by aspirin after acute myocardial infarction（AMI）was established by referring to relevant literature:except for the normal group,the other three groups of rats were ligation of the left anterior descending coronary artery,and then given 0.2g kg-1 aspirin intragastrically for 4day.and given corresponding drugs for 7 day in the OME group and ACP group.The ECG of AMI model was observed.Pathological changes of gastric mucosa were observed under macroscopic and microscope.The contents of PGE₂and VEGF in serum and the contents of TXB₂,6-Keto-PGF1α,t-PA and PAI-1 in plasma were detection by ELISA.PT,TT and FIB in plasma were determined by coagulation.Immunohistochemical method was used to detect the expression of Keap1 and LC3 in gastric tissues of rats.The expression levels of Nrf2,HO-1,NQO1,Beclin1,LC3,P-ERK1/2,CX43 and Occludin in gastric tissues were detected by Western blot.Results:1.Effects of ACP on pathological changes of gastric tissue and gastric mucosal injury index in rats treated with aspirin after acute myocardial infarctionThe normal group had normal stomach morphology,no hyperemia and erosion of mucosa,and no inflammatory cell infiltration.Large amount of food residue was observed in the gastric cavity of model group,and the gastric volume increased,the wall became thinner,and there were ulcer hemorrhagic spots and mucosal shedding,Microscopically,gastric mucosa was observed to be disordered,the mucosal epithelium was absent and flaked off,there were more inflammatory cells infiltrating in the submucosa,and blood vessels were obviously dilated.The gastric mucosa injury index was significantly higher than that of the normal group（P<0.01）.The gastric body of the rats in the ACP group and OME group did not increase,but the shape was normal,the gastric mucosa was slightly hyperemic,the ulcer bleeding points were significantly reduced,and the folds were more regular,Microscopically,the gastric mucosa structure was intact,no mucosal epithelial shedding,reduced inflammatory cell infiltration,regular glandular arrangement,no mucosal shedding and other pathological changes were observed,and the gastric mucosal injury index was significantly lower than that of the model group（P<0.01）.2.Effects of ACP on PGE2,VEGF in serum and PT,TT,FIB,TXB2,6-Keto-PGF1α,T-PA and PAI-1 in plasma of ratsCompared with normal group,the contents of PGE₂and 6-keto-PGF1αin serum of model group were decreased（P<0.05）,VEGF,TXB₂and PAI-1 were significantly decreased（P<0.01）,The contents of t-PA and FIB increased（P<0.05,P<0.01）,PT and TT prolongation（P<0.01,P<0.05）;Compared with model group,the contents of PGE₂,TXB₂,6-Keto-PGF1α,PAI-1 and VEGF in serum of ACP group and OME group were significantly increased（P<0.01）,The contents of t-PA and FIB decreased（P<0.05,P<0.01）,PT and TT decreased in OME group（P<0.05）,PT and TT in Aconitum chishi pills group were significantly reduced（P<0.01）.3.Expression of Keap 1 and LC3 proteins in gastric tissues of rats by ACPCompared with normal group,Keap 1 and LC3 were more expressed in gastric tissue of model group;Compared with model group,the expressions of Keap 1 and LC3 in gastric tissues of aconitum and Omeprazole groups were significantly decreased.4.Effects of ACP on the expression of Nrf2,HO-1,NQO1,Beclin1,LC3 and P-ERK1/2,CX43 and Occludin in gastric tissues of ratsCompared with normal group,the expression of Nrf2,HO-1,NQO1,CX43 and Occludin in gastric tissue of model group decreased（P<0.01）,Beclin1,LC3,p-ERK1/2 expression increased（P<0.01）;Compared with model group,the expressions of Nrf2,HO-1,NQO1,CX43 and Occludin in gastric tissues of rats in ACP groups increased（P<0.01）,Beclin1,LC3,p-ERK1/2 expression decreased（P<0.01）.Conclusion:ACP can reduce the injury degree of gastric mucosa injury and reduce the occurrence of bleeding in rats treated with aspirin after acute myocardial infarction.Its mechanism may be related to promoting the release of protective factors such as PGE₂and VEGF,regulating the balance of coagulation-fibrinolysis system,and activating oxidative stress and autophagy signaling pathways.