The Study Of Eucommia Pollen On Blood Pressure Reduction And Its Mechanism In Spontaneously Hypertensive Rats

Objective:The aim of this study is to evaluate the antihypertensive effects of Eucommia ulmoides pollen and explore the mechamins of antihypertensive effects on hypertensive rats.Materials and methods:50 spontaneously hypertensive rats were divided into model group（distilled water at 1.0 mL/kg/d,SHR group）,perindopril group（administered perindopril at 1.0 mL/kg/d）.Medicine,Eucommia pollen high,medium and low dose group（according to 0.945 mL/kg/d,0.315 mL/kg/d,0.105mL/kg/d to give Eucommia pollen liquid）and SD rats as 10 normal control group（Distilled water was given at 1.0 mL/kg/d,SD group）.All experimental rats were administered on time at 9:00 every day and were measured with a smart non-invasive blood pressure meter 4 hours after the daily administration for 7weeks.The rats were fasted and freely drinked for 24 h.The rats in each group were weighed and anesthetized by intraperitoneal injection of 10%chloral hydrate at 3 mL/kg.The anesthetized rats were fixed on a rat table,the skin and peritoneum were cut,the intestinal tissue was removed,and the abdominal aorta was taken for blood.The content of snoring factor nitric oxide（NO）,endothelium-derived hyperpolarizing factor（EDHF）,prostacyclin（PGI₂）,angiotensin II（Ang II）and endothelin 1（ET-1）in the serum of each group rats were detected by ELISA.Real time PCR method was used to detect the mRNA expression of ACE2 and Mas gene in the rat kidneys;The protein expression of ACE2 and Mas in rat kidneys was detected by Western blot;The thoracic aorta was removed and fixed in 4%paraformaldehyde,and the expression of type I and III collagen and TGF-?₁ in the thoracic aorta wall of each group were detected by immunohistochemistry.Statistical analysis and correlation analysis of each group were performed using SPSS25.0 software.The data were expressed as mean±standard deviation（x±SD）,and P<0.05 indicated that there was a significant difference.Result:1.Effect of Eucommia ulmoides pollen on systolic blood pressure of tail artery in hypertensive ratsThe systolic blood pressure of the rats in the group of high,middle and low doses of the Eucommia ulmoides pollen was significantly higher than that of the SD group before drug administration.There was no significant difference in systolic blood pressure in the rats at 4 h after administration.After 1 week of continuous administration,the systolic blood pressure of rats in the high,middle and low doses of Eucommia ulmoides pollen was significantly decreased compared with the model group.After 2 weeks of administration,the systolic blood pressure of the rats in the high,middle and low doses of the Eucommia ulmoides pollen group and Perindopril group was significantly lower than that of the model group.The systolic blood pressure of the Perindopril group was lower than that of the high,medium and low doses of Eucommia ulmoides pollen;From 3 weeks after administration to 7 weeks after administration,the systolic blood pressure of rats in the high,middle and low doses of Eucommia ulmoides pollen was significantly decreased compared with the model group.The systolic blood pressure of each group tended to be stable.2.Effect of Eucommia Ulmoides Pollen on Vascular Endothelial Factors in Hypertensive RatsThe contents of NO,EDHF and PGI₂ in the rat plasma of model group were significantly lower than those in the SD rat group.The plasma levels of NO,EDHF and PGI2 in the high dose group of Perindopril group and Eucommia ulmoides pollen were significantly higher than those in the model group.The plasma levels of NO and PGI₂ in the middle dose group of Eucommia ulmoides pollen were higher than those in the model group.The plasma contractile factors AngII and ET-1 in the model group were significantly higher than those in the SD group.The levels of AngII and ET-1 in the high,middle and low dose groups of Perindopril group and Eucommia ulmoides were significantly lower than those in the SHR group.3.Effects of Eucommia Ulmoides Pollen on the expression of ACE2,Mas and Angiotensin 1-7 in Hypertensive RatsThe content of angiotensin 1-7 in the group of high,middle,Perindopril and SD groups of Eucommia ulmoides pollen was significantly higher than that of SHR group.There was no significant difference in the content of angiotensin 1-7 between the low dose group of Eucommia ulmoides pollen and the model group.Compared with the model group,the high,medium and low doses of Eucommia ulmoides pollen,Perindopril group and SD group showed a significant increase in ACE2 and Mas-1 protein content.The expression of ACE2 and Mas mRNA in the kidney of the model group was significantly reduced compared with the SD group.Compared with the model group,the expressions of ACE2 and Mass mRNA were significantly increased in the high,middle and low doses of Eucommia ulmoides pollen,western medicine group and SD group.From the amount of expression,it can be clearly concluded that the middle dose of Eucommia ulmoides pollen is better.4.Effect of Eucommia Ulmoides Pollen on Thoracic Aortic Wall of Hypertensive RatsCompared with the SD group,the expression of type I and III collagen and TGF-?₁ increased significantly.Compared with the model group,the high,middle and low doses of Eucommia ulmoides pollen and the model group showed a significant decrease in collagen expression of I and III.Compared with the model group,the expression of TGF-?₁ was significantly decreased in the high,middle dose and Perindopril groups of Eucommia ulmoides pollen;There was no significant difference in the expression of I,III collagen and TGF-?₁ between the high and middle dose groups of Eucommia ulmoides Oliv.and Perindopril group and SD group.Compared with the SD group,the expression of I,III collagen and TGF-?1 was significantly increased in the low dose group of Eucommia ulmoides pollen.There was no significant difference in the expression of I,III collagen and TGF-?₁ between the Perindopril group and the SD group.Conclusions:1.The high,medium and low doses of Eucommiaulmoides pollen have the effect of lowering blood pressure;after a long-term administration,the effects of high,medium and low doses of Eucommia ulmoides pollen on lowering blood pressure were equivalent to the antihypertensive effect of Perindopril.2.Eucommia ulmoides pollen protects and reduces blood veAssel endothelial function by regulating the levels of endothelin-1,EDHF,PGI₂,AngII and ET-1 in plasma.3.The medium dose of Eucommia ulmoides pollen can promote the expression of protein and mRNA of ACE2 and Mas-1 in the kidney of hypertensive rats,increase the content of Ang1-7 in plasma,leading to the decrese in blood pressure.4.The high and medium doses of Eucommia ulmoides pollen can significantly inhibit the expression of vascular type I and III collagen and TGF-?1,which can repair the blood vessels in hypertensive rats.