Inhibitory effects of Tianma Gouteng Drink on vascular remodeling and its impact on NOX2/ROS pathway and endoplasmic reticulum stress in SHR
Objective To explore the inhibitory effects and related mechanism of Tianma Gouteng Drink on vascular remodeling in spontaneously hypertensive rats(SHR).Methods The rats were randomized into normal control,model,irbesartan,and Tianma Gouteng Drink groups.The rat tail artery pressure was measured weekly during administration.After 4 weeks of administration,the tissue of the thoracic aorta was examined by HE staining;intima-media thickness(IMT)of the thoracic aorta was measured and the IMT/lumen diameter(LD)ratio was calculated;the morphological changes of the thoracic aorta were examined by scanning electron microscopy.Immunohistochemical analysis was performed to determine the protein expressions of NADPH oxidase 2(NOX2),C/EBP homologous protein(CHOP),and glucose-regulating protein 78(GRP78)in the thoracic aorta.ELISA was used to determine the plasma levels of reactive oxygen species(ROS).Results(1)Tail artery pressure measurement:Compared with normal control group,the systolic blood pressure of rats in model group was significantly higher(P＜0.05);compared with model group,the systolic blood pressure of rats in all treatment groups decreased from the first week of administration(P＜0.05).(2)Histomorphological examination of the thoracic aorta:Scanning electron microscopy revealed that the wall of the thoracic aorta in model group was significantly thicker than that in normal control group;compared with model group,the thickness of the thoracic aortic wall was reduced in all treatment groups.HE staining showed that the vascular structure of the thoracic aorta in normal control group was normal,with no evidence of arterial wall proliferation;in model group,the wall of the thoracic aorta was significantly thickened,and the number of nuclei per unit area increased;compared with model group,both the thickness of the thoracic aortic wall and the number of nuclei per unit area were reduced in all treatment groups.Compared with normal control group,the IMT and IMT/LD of the thoracic aorta in model group increased(P＜0.05);compared with model group,the IMT and IMT/LD of the thoracic aorta decreased in all treatment groups(P＜0.05).(3)Immunohistochemical determination of NOX2,CHOP,and GRP78 protein expression levels in the thoracic aorta:Compared with normal control group,the protein expression levels of NOX2,CHOP,and GRP78 in the vascular wall of model group were significantly higher(P＜0.05);compared with model group,the protein expression levels of NOX2,CHOP,and GRP78 in the vascular wall decreased in all treatment groups(P＜0.05).(4)ELISA measurement of plasma ROS level:Compared with normal control group,plasma ROS level in model group significantly increased(P＜0.05);compared with model group,ROS levels of all treatment groups significantly decreased(P＜0.05).Conclusion Tianma Gouteng Drink can inhibit vascular remodeling while lowering blood pressure,and its mechanism may be related to the inhibition of endoplasmic reticulum stress mediated by NOX2/ROS pathway.
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