Study Of The Uncaria Rhynchophylla Total Alkaloids On Intervention Vascular Remodeling In Hypertension And Protection Of Vascular Endothelial Cell Function

This experiment had come from shandong provincial projects:topic Numbers--J05L05.Objective:The recent studies indicate that, primary hypertension pertains to endothelial function obstacle. The ideal antihypertensive medication besides lower blood pressure, still should improve the structure and function of the vascular hypertension, reverse arterial remodeling, and make the function of normal, protect endothelial function and protection of target organs. The Uncaria rhynchOphylla is commonly used medicine for clinical treatment of hypertension. The effective components of the Uncaria rhynchOphylla total alkaloids have high biological activity, having good step-down, resisting myocardial reconstruction and antiarrhythmic effect, but the hypotensive mechanism is unclear. Previous research shows that, total alkaloids lower blood pressure through antihypertensive vascular remodeling, inhibit antihypertensive vascular smooth muscle cell proliferation. The field Inhibiting endothelial cell ageing step-down has not involved. Therefore, this research explored the function and mechanism of the Uncaria rhynchOphylla that antihypertensive vascular remodeling, inhibit endothelial cell aging. And try to open up its by inhibiting endothelial cell senescence-to protect endothelial cell function-reverse the vascular remodeling-lower blood pressure-protect the target organs, an effective way to control the field of hypertension.Methods:In vivo experiments, we took spontaneously hypertensive rats (SHR) as a model. Then we observed the influence of Uncaria alkaloids on the blood pressure of SHR tail artery, on the rat thoracic aorta, mesenteric artery histological and stereological changes, on the rat aorta endothelial ultrastructure, on the Rat aortic endothelialβ-galactosidase expression and telomerase activity expression of the relative. On this basis, we study the effect and possible mechanism of Uncaria rhynchOphylla total alkaloids step-down, improve the effect of vascular remodeling. In vitro experiments, we build RAEC model AngⅡinduced by the proliferation and D-galacitiol induced agingl respectively. We observed the effects of total alkaloid on RAEC proliferation activity by MTT method, on RAEC Ca2+concentration the value of the relative expression by immunohistochemistry, on RAEC group cell cycle By flow cytometry, on RAEC ultrastructure by scanning electron microscopy,on positive rate of aging RAEC byβ-galactosidase staining, on the expression of telomerase activity in RAEC by PCR-ELISA assay and on the apoptosis of aging RAEC. To study the effect and the possible mechanism of Uncaria rhynchOphylla total alkaloids that AngⅡRAEC induced by inhibiting proliferation, restrain D-galacitiol RAEC induced aging and promote aging RAEC apoptosis.Results:The vivo experiments show that RTA can reduce the total alkaloid SHR tail arterial blood pressure and has very obvious difference compared with the model group(P<0.01). Comparing with the model group, the RTA group, mesenteric artery and the thoracic aorta film thickness/lumen diameter ratio reduced significantly(P<0.05). The results of thoracic aortic endothelial scanning electron microscope shows that the RTA group s endothelial form structure were obviously improvedCompared comparing with the model group. It performances that endothelial cells aligned with a smooth surface, the cell shedding reduced obviously and lining damage ligtening obviously. The thoracic aortic endothelial rats beta galacitiol nucleoside enzyme expression of the RTA group reduced significantly compareing with the model group (P <0.05). AT the same time, the thoracic aortic endothelial rats relative express telomerase activity of the RTA group reduced significantly compareing too with the model group (P<0.05). The vitro experiments indicate that:The MTT experiments showed thatⅡangiotensin significantly promote RAEC proliferation, the Total alkaloid can inhibit the proliferation of angiotensinⅡ-induced RAEC, the RAEC Ca2+concentration of the RTA group significantly reduce relative to express (P<0.05), It was found that G1 period became high (P<0.05) and S period became lower (P<0.01) in the RTA group, and the RTA blocked the transform from G0/G1 period to synthesis of DNA period, so that theRAEC proliferation was inhibited. RAEC ultrastructure scanning electrometry microscopy showed that the RAEC morphological structure of the RTA group improved obviously, such as the cell morphology and size and microvilli quantity and distribution. Beta galacitiol nucleoside enzymes stain shows that D-galacitiol has obvious effect of RAEC induced aging, the rate of senescent cells of the RTA group reduced obviously (P<0.01). Detection of telomerase activity were significantly lower compareing with the model group (P<0.05). The RTA can improve senescence endothelial cell apoptosis significantly(P<0.05).Conclusion:This medicine opened a new field for traditional Chinese medicine to control of hypertension,though the effective way that inhibitting endothelial cells-protecting endothelial function-reversing vascular remodeling-reducing blood pressure-protecting target organs. Research shows that RTA can significantly reduce the total alkaloid SHR tail arterial blood pressure.It has an significant function to lower blood pressure. The RTA has the obvious improvement, vascular remodeling of reverse hypertension. It can improve sendothelial function and structure and protect endothelial function and inhibit endothelial function of aging significantly. The RTA can inhibit Ang II RAEC proliferation-promoting effect. For D-galacitiol mediated RAEC aging has obvious inhibition. The RTA can obviously improve the structure and function of the RAEC. The RTA can reduce positive senescent cells and the telomerase activity. The RTA can inhibit the RAEC aging significantly. The RTA can improve senescence endothelial cell apoptosis significantly.