Co-administered telmisartan and calcium dobesylate to inhibitors inflammation in aortic of spontaneous hypertension via the miR-19b-3p/SOCS1 axis
Objective To investigate the protective effect and mechanism of telmisartan and calcium dobesilate on aorta in rats with spontaneous hypertension.Methods Spontaneously hypertensive(SHR)rats and their WKY rats were randomly divided(n=6)into control group(WKY),SHR group,telmisartan group,calcium oxybenesulfonic acid group and combined treatment group.He-matoxylin-eosin staining was used to observe the changes of aortic vessels before and after treatment.The expression level of inflamma-tory factors was detected by ELISA.The downstream target genes of miR-19b-3p were predicted by TargetScan,and the binding rela-tionship between miR-19b-3p and downstream target genes was verified by double luciferase assay.The expression levels of miR-19b-3p and SOCS1 were detected by qRT-PCR.Cells were divided into:control group,temesartan+NC group,NC+CAD group and temesar-tan+CAD group.Subsequently,in order to verify the regulatory relationship between temesartan and calcium hydroxybenzenesulfonate and miR-19b-3p/SOCS1 signaling axis,VSMC cells were treated with temesartan and calcium hydroxybenzenesulfonate alone or in combination.Cell were grouped into:blank group,miR-19b-3p inhibitoror group,miR-19b-3p inhibitor+timisartan+NC group,miR-19b-3p inhibitor+NC+CAD group,miR-19b-3p inhibitoror+timisartan+CAD group.Vascular Smooth Muscle cells(VSMC)were isolat-ed from the aorta of spontaneously hypertensive rats.The effects of telmisartan and calcium isobenesulfate on cell proliferation,migra-tion phenotyping and expression of inflammatory factors were investigated by CCK-8,Transwell laboratory assay,qRT-PCR and WB.Results Compared with the control group,the aortic wall thickness was significantly thickened and the lumen inner wall was de-creased in the SHR+NC group;the thickness of the thoracic aortic wall was decreased and the lumen radius was increased in SHR rats via SHR+timisartan and SHR+CAD groups.ELISA results showed that the expression levels of IL-1β,TNF-α,and IL-6 in the blood of rats in the SHR+NC group were significantly increased compared with those in the control group(P<0.05),and the expression levels of inflammatory factors in the rats in the SHR+timisartan,SHR+CAD,and timosartan+CAD groups were significantly decreased compared with those in the SHR+NC group(P<0.05).Compared with the expression level of miR-19b-3p in the aorta of the control group,it was significantly higher in the SHR+NC group and significantly lower in the SHR+timisartan and SHR+TAD groups(P<0.05).The qRT-PCR results showed that the expression level of SOCS1 was significantly decreased in the SHR+NC group compared with the control group,and significantly up-regulated in the SHR+timisartan,SHR+CAD,and timisartan+CAD groups,compared with the SHR+NC group(P<0.05).The results of qRT-PCR showed that the expression level of miR-19b-3p in aorta of SHR rats was significantly de-creased in VSMC cells in the temesartan+NC,NC+CAD and temesartan+CAD groups compared with the control group(P<0.05).The results of transwell assay showed that the migration of VSMC cells was significantly decreased in the temosartan+NC,NC+CAD and te-mosartan+CAD groups compared with that in the control group(P<0.05).Compared with the blank group,the expression levels of IL-1β and TNF-α were significantly reduced in the miR-19b-3p inhibitor group,which was enhanced by further addition of temosartan and calcium hydroxybenzenesulfonate treatment(P<0.05).Conclusion Telmisartan combined with Calcium Dobesylate to relieve the aortic-injury and inhibitor the expression of inflammatory factors in spontaneous hypertension via the miR-19b-3p/SOCS1 axis.
telmisartancalcium dobesilatemiR-19b-3psuppressor of cytokine signaling-1spontaneous hypertensioninflammatory
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