| Objective: Observation of Compound Gouteng Zhixuan Tablets on spontaneously hypertensive rats(SHR)tail artery pressure,thoracic aorta morphology changes,P2Y6 receptor(P2Y6R),nuclear factor κB RelA(NF-κB p65),tumor necrosis factor-α(TNF-α)expression,to explore its regulatory effect on vascular endothelial inflammation in the early stage of hypertension.Methods: The 48 SHRs were randomly divided into 6 groups,8 in each group,namely: model group,Compound Gouteng Zhixuan tablets group,Irbesartan tablets group,MRS 2578 group,Compound Gouteng Zhixuan tablets + MRS 2578 group,Irbesartan tablets + MRS 2578 group.The model group was gavage with distilled water;the Compound Gouteng Zhixuan tablet group was gavage with the Compound Gouteng Zhixuan tablet suspension;the Irbesartan tablet group was gavage with Irbesartan tablet suspension;the MRS 2578 group was treated with P2Y6R the antagonist MRS 2578 solution was injected intraperitoneally;the Compound Gouteng Zhixuan tablets + MRS 2578 group was administered with the Compound Gouteng Zhixuan tablets suspension and the MRS 2578 solution was injected intraperitoneally;the Irbesartan tablets + MRS 2578 group was given Irbesartan the tablet suspension was intragastrically administered and the MRS 2578 solution was injected intraperitoneally.All rats intervened continuously for 4 weeks,once a day.One week before the start of the experiment and 2 days a week after the treatment,the tail artery blood pressure of each rat was measured 3 times by non-invasive rat tail artery manometry,and the average value of the systolic blood pressure of the 3 times was taken as the blood pressure value of the week.The body weight was measured and recorded on the 7th day of each week,and the dosage was adjusted according to the body weight.After 4 weeks of drug intervention,samples were taken,serum and thoracic aorta were separated,the morphological changes of SHR thoracic aorta were observed by HE staining method,TNF-α concentration in serum was determined by ELISA method,and RT-PCR method was used to detect the gene expression of P2Y6R and NF-κB p65 in the thoracic aorta.Results:(1)SHR tail artery systolic blood pressure before and after intervention:After 4 weeks of drug intervention,the Compound Gouteng Zhixuan tablet group,Irbesartan tablet group,MRS 2578 group,Compound Gouteng Zhixuan tablet + MRS 2578 group,Irbesartan tablet + MRS 2578 group of the systolic blood pressure was lower than before the intervention,and the difference was statistically significant;the systolic blood pressure of the model group did not change significantly before and after the intervention,and the difference was not statistically significant.(2)HE staining method to observe the morphological changes of SHR thoracic aorta: the model group has complete tube wall structure,local intima is damaged,hyperplasia,and media smooth muscle cell arrangement is disordered;Compound Gouteng Zhixuan tablets group,Irbesartan tablets and the MRS 2578 group the tube wall structure is complete,the intima is locally uneven,damaged or hyperplasia,and the smooth muscle layer and elastic fibers of the media have no obvious pathological changes;Compound Gouteng Zhixuan tablets + MRS 2578 group,Irbesartan tablets +MRS 2578 group,the tube wall structure was intact,the intima was smooth and flat,the morphology and structure were normal,and the media smooth muscle layer and elastic fibers had no obvious pathological changes.(3)Determination of TNF-α concentration in serum by ELISA method:Compared with the model group,the concentration of serum TNF-α in each group of Compound Gouteng Zhixuan tablets,Irbesartan tablets group,MRS2578 group,Compound Gouteng Zhixuan tablets + MRS 2578 group,and Irbesartan besartan tablets + MRS 2578 group,the difference was statistically significant.Compared with the Compound Gouteng Zhixuan group,the Irbesartan tablet group,and the MRS 2578 group,the Compound Gouteng Zhixuan tablets + MRS 2578 group and the Irbesartan tablets +MRS 2578 group have lower serum TNF-α concentration,and the difference was statistically significant.(4)Using RT-PCR method to detect the gene expression of P2Y6R and NF-κB p65 in the thoracic aorta: Compared with the model group,the Compound Gouteng Zhixuan tablets group,Irbesartan tablets group,MRS2578 group,Compound Gouteng Zhixuan tablet + MRS 2578 group and Irbesartan tablet + MRS 2578 group,each group of thoracic aorta P2Y6R and NF-κB p65 gene expression were all decreased,and the difference was statistically significant;Compared with the Compound Gouteng Zhixuan tablet group,Irbesartan tablets group and the MRS 2578 group,the Compound Gouteng Zhixuan tablets + MRS 2578 group and the Irbesartan tablet + MRS 2578 group have lower gene expression of P2Y6R and NF-κB p65 in the thoracic aorta,and the difference was statistically significant.Conclusion:(1)Compound Gouteng Zhixuan Tablets can effectively lower SHR blood pressure.(2)Compound Gouteng Zhixuan Tablets can regulate the early vascular endothelial inflammation of hypertension,and its mechanism may be to reduce the early vascular endothelial inflammation of hypertension by down-regulating the expression of P2Y6R,NF-κB p65 and TNF-α,thereby achieving the effect of lowering blood pressure. |
