Study on the Effect and Mechanism of Dapagliptin on Blood Pressure in Desoxycorticosterone Salt Sensitive Hypertensive Rats
Objective To explore the effect and mechanism of dapagliptin on blood pressure in desoxycorticosterone(DOCA)salt sensitive hypertensive rats.Methods Fifty specific pathogen free(SPF)Wistar rats were selected from March to July 2023,and 10 rats were selected as blank group(n=10,given distilled water intragastric administration).The remaining 40 rats were established in salt-sensitive hypertension model,and then randomly divided into model group(n=10,given distilled water intragastric administration),enalapril group(n=10,given enalapril intervention),dagliaglozin group(n=10,given dagliaglozin intervention),and dagliaglozin+enalapril group(n=10,given dagliaglozin+enalapril intervention).The pathological tissues were observed of 5 groups,the blood pressure,heart rate,plasma renin activity(PRA),aldosterone(ALD),angiotensin Ⅱ(Ang Ⅱ),endothelin(ET)and mRNA expression levels of interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-α(TNF-α)in myocardial tissue were compared of 5 groups.Results In the blank group,the myocardial tissue was arranged neatly without inflammatory cell infiltration;in the model group,myocardial fibers were disordered and inflammatory cells infiltrated seriously;the myocardial fiber arrangement and inflammatory cell infiltration were improved in enalapril group,dagliazin group and dagliazin+enalapril group,especially in dagliazin+enalapril group.The blood pressure and heart rate of model group,enalapril group,dagliprazin group and dagliprazin+enalapril group were higher than those of blank group,and the differences were statistically significant(P<0.05);the blood pressure[(130.12±20.45)mmHg,(129.41±20.36)mmHg,(113.49±11.34)mmHg]and heart rate[(145.35±16.89)beats/min,(146.01±16.60)beats/min,(130.01±14.89)beats/min)]of enalapril group,dapagliflozin group and dapagliflozin+enalapril group were significantly lower than those of the model group[(156.49±24.34)mmHg,(163.89±20.01)beats/min],and the differences were statistically significant(P<0.05);the blood pressure and heart rate of dapagliflozin+enalapril group were lower than those of enalapril group and dapagliflozin group,and the differences were statistically significant(P<0.05);there were no significant differences in blood pressure and heart rate between enalapril group and dapagliflozin group,the differences were not statistically significant(P>0.05).PRA[(6.23±0.72)μg/L,(5.30±0.65)μg/L,(5.28±0.64)μg/L,(4.46±0.51)μg/L],ALD[(1.12±0.14)μg/L,(0.90±0.10)μg/L,(0.89±0.11)μg/L,(0.56±0.07)μg/L],AngⅡ[(23.89±2.83)ng/L,(20.89±2.01)ng/L,(20.76±2.02)ng/L,(17.25±1.60)ng/L],ET[(6.12±0.72)％,(5.10±0.61)％,(5.05±0.62)％,(4.27±0.35)％]in model group,enalapril group,dapagliflozin group,dapagliflozin+enalapril group were significantly higher than those in the blank control group[(3.95±0.21)μg/L,(0.39±0.04)μg/L,(15.75±1.46)ng/L,(3.25±0.30)％],the differences were statistically significant(P<0.05);the levels of RA,ALD,Ang Ⅱ and ET in enalapril group,dagliprazin group and dagliprazin+enalapril group were lower than those in model group,and the differences were statistically significant(P<0.05).The PRA,ALD,Ang Ⅱ and ET levels of dagliazin+enalapril group were lower than those of enalapril and dagliazin groups,and the differences were statistically significant(P<0.05).There were no significant differences in PRA,ALD,Ang Ⅱ and ET levels between enalapril group and daglipzin group,the differences were not statistically significant(P>0.05).Conclusion Daglipzin can effectively reduce blood pressure,heart rate,PRA,ALD,Ang Ⅱ and ET in DOCA salt-sensitive hypertensive rats,regulate mRNA expression of IL-10,TNF-α and IL-6,inhibit inflammatory response and improve myocardial fibrosis.
万方数据
维普
