Study On The Mechanism Of "Gastrodia Elata-Danshen Combination" On Vascular Endothelial Injury In Spontaneously Hypertensive Rats Based On PERK Pathwa

Objective:By observing the effects of "Gastrodia elata-Salvia miltiorrhizan combination" on blood pressure,HE staining of thoracic aorta and the expression of GRP78,CHOP and Caspase-12,which are the signature proteins of PERK pathway in spontaneously hypertensive rats(SHR),we investigated the efficacy of "Gastrodia elata-Salvia miltiorrhizan combination" on hypertension and the mechanism of its effects on improving vascular endothelial injury.Methods:Thirty male SHR rats were randomly divided into model group,western medicine group and "Gastrodia elata-Salvia miltiorrhizan combination" small,medium and large dose groups,six rats in each group,and six WKY male rats were set up as blank control group,a total of six groups.The rats in the western medicine group were gavaged with 0.72mg/kg of Candesartanate suspension,while the rats in the small,medium and large dose groups were gavaged with 2.43g/kg,4.86g/kg and 9.72g/kg of "Gastrodia elata-Salvia miltiorrhizan combination" respectively.The model group and the blank group were gavaged with sterile distilled water in equal amounts for 8 weeks.During this period,blood pressure changes were measured by non-invasive blood pressure testing;pathological changes in the thoracic aorta were observed by HE staining;the results of GRP78,CHOP and Caspase-12 protein quantification in the abdominal aorta were measured by western blotting.Results:1.Blood pressure results: Before the drug intervention,the blood pressure of rats in the model group,western medicine group and "Gastrodia elata-Salvia miltiorrhizan Combination" small,medium and large dose groups were significantly higher compared with that of rats in the blank group(P<0.01);After the drug intervention,the blood pressure of the rats in the western medicine group and "Gastrodia elata-Salvia miltiorrhizan Combination" small,medium and large dose groups were significantly lower compared with that of the rats in the model group(P<0.01).2.HE staining results: After the drug intervention,compared with the blank group,the thoracic aorta of rats in the model group had obvious endothelial injury,abnormal endothelial cell morphology,swelling,shedding cells,incomplete endothelial structure and thickened endothelium;compared with the model group,the thoracic aorta of rats in the western medicine group and "Gastrodia elata-Salvia miltiorrhizan combination" small,medium and large dose groups had less injury and less endothelial cells.The endothelial cell morphology,intima-media structure and thickness were all improved to different degrees.3.Immunoblotting results: After drug intervention,the expression of GRP78,CHOP and Caspase-12 in the abdominal aorta of rats in the model group was significantly increased compared with that in the blank group(P<0.01);the expression of GRP78,CHOP and Caspase-12 in the abdominal aorta of rats in the Western medicine group and the small,medium and large dose groups of "Gastrodia elata-Salvia miltiorrhizan combination" were significantly decreased compared with that in the model group(P<0.01);the expression of GRP78,CHOP and Caspase-12 protein in the abdominal aorta of the rats in the medium and high dose groups of "Gastrodia elata-Salvia miltiorrhizan combination" were significantly decreased compared with that in the western group(P<0.01).Conclusion:1."Gastrodia elata-Salvia miltiorrhizan combination" can reduce blood pressure in spontaneously hypertensive rats and improve endothelial injury induced by hypertension.2."Gastrodia elata-Salvia miltiorrhizan combination" may inhibit endoplasmic reticulum stress by down-regulating the expression of PERK signaling pathway proteins GRP78,CHOP and Caspase-12,thus improving vascular endothelial injury.