| Objective:1 To investigate the effect of Magnolin on blood pressure in primary hypertensive rats and secondary hypertensive rats.2 To investigate the effect of Magnolin on the uncoupling of eNOS in thoracic aorta of SHR rats,and then to reveal the mechanism of anti-eNOS uncoupling of Magnolin.Method:1 Modeling method of secondary hypertension rats: 32 SD rats were randomly divided into two groups: ligation of left renal artery with silk suture,and with a 0.2 mm U-shape clamp,after the model had been established,the hypertension SD rats were divided into five groups according to the principle of random sampling: model group,captopril group(40 mg/kg),Magnolin groups with high(80 mg/kg),middle(40 mg/kg)and low(20 mg/kg)doses respectively.Each group was administrated for 7 days.2 Spontaneously hypertensive rats(SHR)were adaptively fed for one week and were randomly divided into five groups: SHR group,captopril group(40 mg/kg),Magnolin groups with high(100 mg/kg),middle(20 mg/kg)and low(4 mg/kg),normotensive Wistar Kyoto rats as control(WKY group).The blood pressure were measured by tail cuff method before and after administration,food intake and water intake of rats were measured,each measurement was taken three times for a period of time,intragastric 7d monitoring in rats after administration of food intake,water intake and blood pressure of three indicators,and the indicators of the results recorded before and after drug intervention the data for statistical analysis.3 The rats were sacrificed to collect heart and thoracic aorta after stomach perfusion a week,The changes of diastolic function of thoracic aorta which were intervened by SHR were detected by the system of isolated vascular strips.4 Western Blot method was used to evaluate the effect of Magnolin intervention on the level of eNOS protein subunit in thoracic aorta of SHR rats.5 The relative changes of protein and mRNA contents of NADPH oxidase subunits(p91phox;p22phox)were determined by Real-time PCR and Western blot.The effects of Magnolin on NADPH oxidase subunits were investigated at the protein expression level.6 The content of malondialdehyde(MDA)in the thoracic aorta of SHR model group and SHR Magnolin intervention group was measured by colorimetric method,to investigate the effects of magnolin intervention on oxidation level.Result:1 The blood pressure of the silk group and the silver clip group were increased gradually.after operation 9 weeks,the blood pressure of the two groups were increased significantly and remained stable,but there was no significant difference between the two groups.Compared with the model group,the blood pressure of Captopril group and Magnolin group decreased significantly after 7 days of drug intervention,the difference was statistically significant(P<0.05),but there was no statistically significant difference in blood pressure between each dose group of Magnolin.2 Compared with SHR group,the compression pressure was significantly decreased in the Captopril group and the Magnolin high dose group at 7 days after the intervention,the difference was statistically significant.Compared with the SHR group,the compression pressure of the low dose group was lower,but the difference was not obvious,there was not statistically significant.The diastolic blood pressure in the Captopril group and the Magnolin intervention group were significantly lower than that in the control group.The difference was statistically significant,but the difference between the groups is not obvious,Magnolin has a significant role in lowering blood pressure.3.Effects of Magnolin on Sodium Nitroprussid(SNP)and Acetylcholine(Ach)on vasodilatation in SHR rats,compared with the SHR group,the vasodilator curve of SNP in the treatment group was not significantly shifted,it is indicated that there was no effect of Magnolin on the relaxation of vasodilators dependent on smooth muscle.The Ach vasodilator curve was significantly shifted in the Magnolin intervention group.4 According to the results of Western blot,Magnolin significantly inhibited expression of gp91-phox protein,but the inhibitory effect on p22-phox protein was not significant.Conclusion: Magnolin can reduce the diastolic blood pressure and systolic blood pressure in primary hypertensive rats and renal hypertensive rats,both of primary hypertension and secondary hypertension have a certain antihypertensive effect.Its mechanism may be related to the inhibition of gp91-phox protein expression with magnolin,reduce oxidative stress,and thus inhibit eNOS uncoupling,and the protection of vascular endothelium. |
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