| Background:The proliferation of vascular smooth muscle cells (VSMC) is a central event in the pathogenesis of atherosclerosis, hypertension, coronary heart disease, postangioplasty restenosis, so to investigate the drug which can inhibit the proliferation of VSMC is the key event for people to reseach.Cellular proliferation is governed by the cell cycle, which comprises 4 distinct sequential phases (G1, S, G2, M). There are two transtion in the cell cycle including G1-S transition and G2-M transition, and the G1-S transition which is effected by a lot of intracellular regulate factor and extracellular stimulation is more important. Progression which is from the G1 phase to the S phase is regulated by a number of of cyclin and serine/threonine protein kinases known as cyclin-dependent kinase (CDK) complexes. P21 and p27 are both member of cyclin-dependent kinase inhibitor family, and inhibit the cyclin-CDK activity leading to GI arrest. P27 is constitutively expressed in normal arteries, is downregulated after arterial injury, becomes upregulated during the later phases of arterial repair, and is inversely correlated with VSMC proliferation. P21 is not expressed in normal arteries, becomes upregulated during the later phases of arterial repair, and also is inversely correlated with VSMC proliferation. A deficiency of p27 in mice leads to benign hyperplasia in multiple organs, but itdoes not directly produce tumors. All of these indicate that p21 and p27 are both negatively related to VSMC proliferationNF-B is one of transcription factor which have the function of transcription and activation and is heterodimers which is constituted with two subunits p50and p65. In the inactive cell, NF- B is retained in the cytoplasm in an inactive state through interaction with represser protein I K B(36 kD). I B can inhibit the nucleic localization signal of NF-B and make it retain in the cytoplasm in the style of inactive compound. I K B family includes I B, I B , I B and so on, and the I B a is most important and is researched most deeply.When the cell is stimulated by the foreign signal, I B is inactivated by phosphorylation, then NF-B can entrance the nucleus and facilitate the express of gene by activating the B enhancer and promotor.It is very important that NF-B can regulate the express of gene which is very related to inflammation, cell differentiation and cell proliferation.Recent research show that NF-B can regulate and transcript the expression of cyclooxygenase-2 gene.Cyclooxygenase-2 is rate-limiting enzyme of prostaglandin synthesis and is absent in quiescent cell,but it's expression increased obviously when it is stimulated by blood serum, cytokine, mitogen and other factor.And when cyclooxygenase-2 is induced and express, a lot of prostatic product is released.Wilson's research show that cyclooxygenase-2 is obviously related to proliferation of VSMC during TNF- a and angiotensin II induced cell proliferation. Recent research indicates that the expression of cyclooxygenase-2 increase obviously in the atherosclerosis vessel, but it is not detected in normal vessel. All of these indicate that the expression of cyclooxygenase-2 is positively related to proliferation of VSMC and atherosclerosis.Parthenolide ( sesquiterpene lactone ) is extract from feverfew (Tanacetum),it's main component is sesquiterpene , it is commanly used in west country and is mainly used to therapy skin infection, rheumatic disorder, migraine. But recent research indicate that parthenolide can regulate many pathway of signal in the cell, inhibit the cyclooxygenase, TNF- a, interleukin-1 expression induced by lipopolysaccharide in macrophage, inhibit the iNOS expression in human monocyt, inhibit the activity of NF- K B in Hela cell, inhibit the growth of tumor cell and can relieve the myocardial ischemical reperfusion injury and so on.But the invention research about the effection of parthenolide on the VSMC is very rare in the world, so we do some research about the effection of inhibition of parthenpolide...
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