Magnesium Lithospermate B, an Active Extract of Salvia miltiorrhiza, Mediates sGC/cGMP/PKG Translocation in Experimental Vasospasm. (2nd April 2014) - Chang, Chih-Zen
Abstract : Background . Soluble guanylyl cyclases (sGCs) and Ras homolog gene family, member A (rhoA)/Ras homolog gene family kinase(rho-kinase) plays a role in vascular smooth muscle relaxation in subarachnoid hemorrhage (SAH). It is of interest to examine the effect of MLB on rhoA/ROCK and sGC/cGMP/PKG expression. Methods . A rodent SAH model was employed. Tissue samples were for sGC α 1, sGC β 1, PKG, rhoA, ROCK (Western blot), and cGMP (ELISA) measurement. Results . MLB morphologically improved convolution of the internal elastic lamina, distortion of endothelial wall, and necrosis of the smooth muscle in the SAH rats. Expressed cGMP, sGC α 1, sGC β 1, and PKG in the SAH groups were reduced (P < 0.01 ), and MLB precondition significantly induced cGMP, sGCα 1, sGCβ 1, and PKG. L-NAME reversed the vasodilation effect of MLB, reduced the bioexpression of PKG and cGMP (P < 0.01 ), and tends to reduce sGCα 1 level and induce rhoA, ROCK level in MLB precondition + SAH groups. Conclusion . These results demonstrate that sGC/cGMP/PKG and NO/ET pathways play pivotal roles in SAH-induced vasospasm. Through activating sGC/cGMP/PKG pathway and partially by inactivating rho-kinase in a NO-dependent mechanism, MLB shows promise to be an effective strategy for the treatment of this disease entity.