Effects Of Notch1 Signaling Pathway Mediated NSAID On Cardiac Structure And Function In Rats With Pressure Overload Myocardial Hypertrophy

Object:To study the effects of aspirin and celecoxib on the cardiac structure and function of stress overload myocardial hypertrophy rats,and whether the protective effect was achieved by regulating the Notch 1 signaling pathway.Methods:180 SPF SD rats were randomly divided into normal control group,sham operation group,model group,model+Celecoxib group and model+Asprin group.At 8weeks,10 weeks,12 weeks and 14 weeks,the tail artery was measured by noninvasive tail artery manometer;the structure and function of left ventricle were detected by echocardiography;the contents of plasma inflammatory factors TNF-α,IL-10 and PGI₂were detected by Elisa;the left ventricle was weighed to calculate the left ventricular mass index;the morphology of myocardial cells was observed by HE staining;the content of collagen fibers was detected by Masson staining;the expression of collagen fibers was detected by immunohistochemistry the expression and distribution of related proteins were detected by immunohistochemistry;the content of related m RNA was detected by fluorescence quantitative PCR.Results:（1）tail artery pulse pressure:the arterial pressure（systolic pressure,diastolic pressure）of the model group was significantly higher than that of the normal control group（P<0.05）.The blood pressure of Celecoxib group and Asprin group began to decrease from 12weeks,and there was no significant difference between the two groups at 14 weeks.（2）Echocardiography showed that the systolic function of the model group decreased significantly,EF and FS gradually decreased with time compared with the normal control group（P<0.05）.（3）left ventricular mass index of the model group increased significantly（P<0.05）.Asprin group decreased from 10 weeks,Celecoxib group decreased from 12 weeks,and there was significant difference compared with the control group at 14 weeks（P>0.05）.（4）Results:the levels of IL-10 and TNF-αin the model group increased gradually compared with the other four groups（P<0.05）;the content of PGI₂ decreased gradually compared with the other four groups（P<0.05,P<0.01）.The levels of TNF-α,IL-10 and PGI₂in aspirin group and Celecoxib group were significantly lower than those in model group（P<0.05,P<0.01）.（5）He staining showed that:in the model group,the arrangement of myocardial cells was disordered,the diameter increased and the ischemic area appeared from 8 weeks.In Celecoxib group and Asprin group,the arrangement of cardiomyocytes was slightly irregular,and the diameter of cardiomyocytes was significantly decreased compared with the model group（P<0.05）.（6）Collagen fiber staining showed that cvf-t and cvf-nv increased gradually from 8 weeks in the model group（P<0.05）;collagen fibers proliferated and stroma widened.The content of collagen fibers in Asprin group and celecoxib group was significantly lower than that in model group（P<0.05）.（7）Fluorescent quantitative PCR results:Notch1 receptor m RNA and HEY2 m RNA increased in the model group,and were significantly higher than the other four groups at each time point;Asprin group decreased from 10 weeks,celecoxib group decreased from 12 weeks.（8）Immunohistochemical results:the content and distribution of Notch-1 receptor protein:the model group entered the cardiac plasma from the myocardial cell membrane,and the time compliance increased;aspirin group transferred from the cell membrane to the plasma and kept it in the cell membrane,which was not entered into the plasma from low to high to low;the celecoxib group was fed into the plasma from the cell membrane to the cell membrane for 14weeks,and then returned to the cell membrane,which was in the trend with aspirin the group was similar,without peak but platform stage.HEY2 protein content and distribution:the model group was distributed in the interstitial nucleus,and the time compliance increased;aspirin was transferred from the interstitial nucleus to the posterior metaplasm nucleus,and the expression was from low to high to low;the celecoxib group transferred from the cardiac nucleus to the interstitial nucleus and returned to the cardiac nucleus.The overall trend was the same as that of aspirin group,but there was no peak,and the platform stage appeared.Conclusion:NSAID can decrease blood pressure,restore myocardial systolic and diastolic function,and inhibit left ventricular remodeling and hypertrophy in hypertensive rats with myocardial hypertrophy.This effect may be achieved through the regulation of Notch1Signaling Pathway by NSAID.