| Objective: To study the antihypertensive effect and mechanism of Eucommia folium granules.Materials and methods: Eucommia folium granules are extracted by flash extraction method.Eucommia folium granules are formed by one-step granulation method.The quality standard of Eucommia folium granules is established;40 male spontaneously hypertensive rats(SHR)are randomly divided into 5Group,model group,perindopril group,Eucommia folium granules low,medium and high dose groups,8in each group,8 male wistar rats in the blank group.The rats in each group were given by intragastric administration at a dose of 10 m L/kg/d.The rats in the model group and the blank group were given 0.5%CMC-Na solution.The dose in the perindopril group was 0.4 mg/kg.The dosage of granules in the low,medium and high dose groups was 2.06,4.12 and 8.24 g/kg.Rats in each group were given once every day at 9 am for 8 weeks.The nitrate reductase method was used to detect the serum NO content of the rat,and the ELISA kit was used to detect the serum e NOs,Ang II,TNF-α,and IL-6 content;HE and Masson staining were used to detect the morphological changes of the rat thoracic aorta.Changes in ultrastructure of vascular endothelium;Western Blot method to detect changes in Rho A and ROCK 1 protein expression;PCR method to detect changes in Rho A and ROCK 1 gene expression;SPSS 26.0 software was used to process the experimental data,and Graphpad prism 8 was used to plot the results.The data were expressed as means ± standard deviation(`x±s).Result:1 Preparation and quality control of Eucommia folium granulesEucommia folium granules are prepared by flash extraction method and one-step granulation method to obtain particles with uniform particle size,good molding rate and good dissolution.Establish the quality standard of Eucommia folium granules,use TLC to identify chlorogenic acid,and establish the HPLC method for simultaneous determination of peach glucoside,geniposide and chlorogenic acid.2 Effects of Eucommia folium granules on blood pressure in SHR ratsBefore administration,the systolic and diastolic blood pressure of rats in each group were measured.The systolic blood pressure of SHR rats was(161.28±5.31)mm Hg.After 8 weeks ofadministration,the average systolic blood pressure of Eucommia folium granules in low,medium,and high dose groups and perindopril group were(137.52±9.10),(124.74±6.82),(127.14±6.45),(133.41 ±7.71)mm Hg,significantly lower than the model group systolic blood pressure(176.08±5.95)mm Hg(P<0.01).The average diastolic blood pressure of Eucommia folium granules in low,medium and high dose groups and perindopril group were(116.13±8.89),(109.36±12.43),(103.90±16.41),(104.83±8.88)mm Hg The diastolic blood pressure(153.0±2.75)mm Hg was significantly decreased(P<0.01).3 The effect of Eucommia folium granules on serum NO,e NOs,Ang II,TNF-α and IL-6 in SHR ratsCompared with the model group,the levels of serum NO and e NOs in Eucommia folium granules were significantly lower than those in the model group(p<0.05).The serum Ang IIof Eucommia folium granules in low,medium and high dose groups and perindopril group.Content of was significantly increased(P<0.01).Compared with the model group,the levels of TNF-α and IL-6 in the middle and high dose groups of Eucommia folium granules and the perindopril group were significantly reduced((P<0.05),and the low dose groups of Eucommia folium granules were compared with the model group There was no significant difference in serum TNF-α and IL-6 levels(P>0.05),but they all showed a decreasing trend.4 Effect of Eucommia folium granules on vascular endothelial morphology of SHR rats(1)HE staining to observe the effect of Eucommia folium granules on thoracic aorta of SHR ratsIn the model group,the endometrium was obviously damaged,partially shed,unevenly thickened,the medial vascular smooth muscle cells were significantly proliferated,elastic fibers were reduced,and even fractured,and the boundary between the adventitia and the media was blurred;Eucommia folium granules were low,medium,Both the high-dose group and the perindopril group can improve the vascular endothelial morphology to varying degrees.The vascular intima in each group is smoother,the medial muscle fibers are arranged in an orderly manner,and smooth muscle cells and elastic fibers are arranged in a regular manner.(2)Masson staining to observe the effect of Eucommia folium granules on thoracic aorta of SHR ratsCompared with the model group,the low,medium and high dose groups of Eucommia folium granules and the perindopril group had reduced collagen fiber deposition in the adventitia of blood vessels,elastic fibers were ordered and evenly distributed,and the collagen phenomenon between the media cells was obvious Reduced,Eucommia folium granules can significantly reduce the collagen content of thoracic aorta in SHR rats.(3)Observation of the effect of Eucommia folium granules on the ultrastructure of vascular endothelium in SHR ratsThe vascular endothelial morphology of the blank group was normal.The vascular endothelial morphology of the model group was abnormal,the structure was loose,the elastic membrane of the blood vessel was broken,collagen fibers increased,and abnormal organelles appeared.Compared with the model group,the Eucommia folium granules low,medium,and high dose groups and the perindopril group had vascular endothelial morphology tending to be normal,ordered,and abnormal organelles significantly reduced.5 Effects of Eucommia folium granules on Rho A,ROCK 1 protein and gene expression in thoracic aorta of SHR ratsCompared with the model group,the Rho A protein expression of Eucommia folium granules in the middle and high dose groups and the perindopril group was significantly down-regulated(P<0.05),and there was no significant difference in Rho A protein expression between the Eucommia folium granules low dose group and the model group(P>0.05),but there is a tendency to decrease.Compared with the model group in the low,medium and high dose groups of Eucommia folium granules and the perindopril group,the protein expression of ROCK 1 was significantly down-regulated(P <0.05),and that of Eucommia folium granules was low and medium,High-dose group and perindopril group compared with model group,Rho A,ROCK1 gene expression was significantly down-regulated(P <0.05).Conclusions:1 The preparation process of Eucommia folium granules was determined,and the quality standard of Eucommia folium granules was established.2 Eucommia folium granules have a significant effect on reducing blood pressure in SHR rats.3 Eucommia folium granules can significantly increase the serum NO and e NOs levels in SHR rats,can significantly reduce the serum Ang II levels in SHR rats,and can improve vascular endothelialfunction.Eucommia folium granules can significantly reduce the levels of TNF-α and IL-6 in the serum of SHR rats and can inhibit the inflammatory response.4 Eucommia folium granules can improve the morphology of vascular endothelium in SHR rats.5 The middle and high dose groups of Eucommia folium granules can down-regulate the expression of Rho A,ROCK 1 protein and genes in the thoracic aorta of SHR rats,improve the endothelial function damage of hypertensive rats,and achieve the effect of reducing blood pressure. |
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