Study on the Mechanism of Heart-nourshing Decoction in Protecting Vascular Endothelium Based on RhoA/Rock1 Signaling Pathway
Objective:To observe the influence of heart-nourishing decoction on vascular endothelial damage in SD rat models and discuss its mechanism.Methods:All 40 SD male rats were allocated to the blank group,the model group,fasudil group and heart-nourishing decoction group according to random number table method with ten in each group.Normal diet was given to the blank group,the model group,fasudil group and heart-nourishing decoction group were fed normal diet containing 3%L-methionine,for twelve weeks,in order to establish rat models with vascular endothelial damage.After successfully modeling,fasudil group received fasudil hydrochloride intraperitoneally at a dose of 2.7 mg/(kg·d),heart-nourishing decoction accepted intragastric administration of the extract suspension of the decoction at a dose of 2.34 g/(kg·d),the blank group and the model group were perfused with equivalent volume of pure water,they were intervened for four weeks.By the end of the intervention,rats were anaesthetised,weighed and sampled,HE method was used to observe the morphological changes of the vascular endothelium of the thoracic aorta in rats;RT-PCR was applied to detect the expressions of RhoA,Rock1 and eNOS mRNA in thoracic aorta in rats;WB was utilized to measure the expressions of RhoA,Rock1,p-MYPT1 and eNOS protein in rat thoracic aorta.Results:HE staining results displayed that the vascular endothelium was intact and continuous,with no obvious damage,most of the vascular endothelium was detached in the model group,with occasional remnants of endothelium,and the degree of injury was significantly aggravated.The vascular endothelium of rats in the heart-nourishing decoction and fasudil group was basically continuous and intact,and the degree of injury was apparently reduced.The results of RT-PCR and WB showed that the decoction could downregulate the expressions of protein and genes of RhoA/Rock1 signaling pathway(P<0.05),meanwhile it could up regulate the expressions of eNOS protein and gene(P<0.05).Conclusion:The decoction could improve pathological damage of the rat models suffering vascular endothelial damage,and its mechanism might be related to the reduction of RhoA,Rock1 protein and mRNA expression in thoracic aorta and the inhibition of RhoA/Rock1 signaling pathway.
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