ABSTRACT
Alzheimer's disease（AD） is an incipient aging neurodegenerative disease， which increases rapidly along with the development trend of social aging and seriously threatens the health of the people. In the absence of effective preventive measures， it will have an enormous impact on the socio-economic and healthcare system. The study found that abnormal cell signal transduction is a key link in many diseases. Cell signal transduction theory has been widely used to clarify the essence of traditional Chinese medicine visceral image and the mechanism of traditional Chinese medicine. 'Correlation of Liver and Kidney' is one of the core plates of the theory of 'Correlation of Five Organs'， which is suitable for explaining the pathogenesis of complex diseases and the correlation of multiple syndromes， and guiding the prescription of clinical syndrome. Hei Xiaoyaosan， as the first choice compound for the prevention and treatment of AD based on the theory of "Correlation of Liver and Kidney' in our team， can play the effects of prevention and treatment by soothing liver and nourishing blood， strengthening spleen and tonifying kidney， and promoting brain collaterals and dredging viscerab spirit. Based on the theory of 'Correlation of Liver and Kidney'， this paper expounds the pathogenesis of AD from the perspective of traditional Chinese medicine， and puts forward the methods and ideas of the preventing and treating of AD from Ca2+-calcium/calmodulin dependent protein （CaM）/calcium/calmodulin dependent protein kinaseⅡ（CaMKⅡ）-cyclic adenosine phosphate reactive element binding protein （CREB） cell signal transduction pathway by consulting literatures and previous studies.
ABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>Studies have shown that nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is expressed widely in tumor tissues and regulates tumor angiogenesis. However, the results are controversial. This study was to investigate the effect of NO on tumor angiogenesis and its mechanism.</p><p><b>METHODS</b>C57BL/6 mice inoculated with Lewis lung cancer cells were randomly divided into three groups. Mice in the NO group were inoculated with lung cancer cells transfected with eNOS gene, mice in the L-NAME group with L-NAME, an eNOS antagonist, and mice in the control group with normal saline. Plasma concentration of NO and the number of endothelial progenitor cells (EPCs) in peripheral blood were detected . Tumor vessel density, CD133+ cells, and the expression of VEGF-VEGFR in tumor tissues were also measured.</p><p><b>RESULTS</b>Four weeks after inoculation of Lewis cells, tumor volume was significantly larger in control group [ (3022 +/- 401) mm(3)] than in the L-NAME group [ (1204 +/-97) ) mm(3)] and in the eNOS group [(1824 +/- 239) mm(3)] (P<0.01). eNOS protein and NO production increased significantly in Lewis lung cancer cells transfected with eNOS gene. But the number of CD133-positive cells and vessel density in tumors were significantly lower in the eNOS group than in the control group [(48+/-19) / HPF vs. ( 103 +/- 27)/ HPF, (19+/- 7) HPF vs. (31 +/- 9) HPF, P<0.05]. The number of EPCs in peripheral blood was not statistically different between each group. The levels of NO in blood and tumor tissue significantly decreased after the treatment of L-NAME, while the tumor vessel density reduced to 12+/- 5/ HPF (P<0.01, vs. the control group; P<0.05, vs the eNOS transfected group). The number of EPCs in blood and that of CD133-positive cells in tumor tissue were significantly smaller in the L-NAME group than in the control group (P<0.05).</p><p><b>CONCLUSION</b>No derived from eNOS inhibits angiogenesis and tumor growth, which may be due to its suppression on either the mobilization or homing of EPCs via VEGF binding to VEGFR.</p>