Experimental Study On Protective Effects Of Rhynchophylline On Attenuating Cerebral Vasospasm After Subarachnoid Hemorrhage

Objective: Subarachnoid hemorrhage(SAH) is a cerebral vascular accident in presently, which almost owing to cerebral aneurysm rupture, its mortality and disability rate is quite high after the nervous system dysfunction, and nearly 35%patients are died early because of seizures. Most survivors will emerge cerebral vasospasm(CVS). CVS was one of the complications after SAH, which is more serious and common, and is an important factor to influence the survival rate and survival quality of patients. The occurrence of apoptosis in cerebral vascular endothelial cell in CVS after SAH have been demonstrated that the p38 MAPK pathway in cerebral tissue is activated, which induce by CVS in further. The biggest content of Gouteng(Uncaria) was the rhynchophylline(Rhy) alkaloid; studies had shown that, Rhy can inhibit the expression of NF-k B through the P38 MAPK pathway. But so far, Rhy whether can inhibit the apoptosis of vascular endothelial cells by the P38 MAPK pathway to reduce CVS after SAH has not been reported in the literature. Therefore, this study aimed to explore the Rhy wether reduces the CVS after SAH in rats by inhibiting the P38 MAPK pathway.Methods: 120 adult male SD rats were used in this study; establish the SAH model by endovascular puncture method. The animal were randomly divided into three groups, sham operation(Sham) group, SAH model group(SAH+N.S)(intraperitoneal saline 1m L after SAH) and Rhy treatment group(SAH+Rhy10mg/kg)(immediately intraperitoneal inject rhynchophylline 10mg/kg 1m L after SAH). At24 h, magnetic resonance imaging(MRI) measure basilar artery(BA) diameter. And then measure the diameter and the wall thickness of BA by HE staining. In different animal groups, using western blotting and immunofluorescence staining to measure the expression levels of the p-p38 MAPK, p-p53 and cleaved-caspase-3 proteins of BA.Results: At 24 h, Rhy administration group(SAH+Rhy10mg/kg) can significantly increase the diameter of BA compared with the SAH model group(SAH+N.S)confirmed by MRI(P<0.05); SAH+Rhy10mg/kg group can significantly increasethe inner diameter and reduced the thickness of vessel wall of BA compared with the SAH+N.S group by HE staining(P<0.05). In addition, the levels of p-p38 MAPK,p-p53 and cleaved-caspase-3 in BA were significantly reduced by Rhy treatment after SAH by Western blotting. Rhy can reduce the expressions of BA p-p38 MAPK,p-p53 and cleaved-caspase-3 apoptosis proteins in endothelial cells by immunofluorescence after SAH.Conclusion: Rhy can inhibit the expression level of p-p38 MAPK, p-p53 and cleaved-caspase-3 protein of BA to inhibit the P38 MAPK pathway, which inhibit the apoptosis of endothelial cells in BA, reduce the SAH after CVS, ameliorating the severity of cerebral vasospasm.