| Summary: | 碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 95 === Abstract
In ten major causes of the death in Taiwan, cardiovascular disease and hypertension are all relate to atherosclerosis. The main methods to treat coronary artery disease are percutaneous transluminal coronary angioplasty, with or without stent implantation. But within the following 6 months after the operation, nearly 30 - 50％ of the patients have coronary restenosis. Previously, reports showed that cannabinoid system might play a role in the treatment of atherosclerosis. Delta-9-tetrahydrocannabinol, or 6a, 7, 8, 10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d ]-pyran-1-ol, is a substance possessing several stereochemical variants. One of them is (2)-trans-delta-9-tetra-hidrocannabinol, also called dronabinol or D9-THC. Two known cannabinoid receptors are namely CB1 and CB2 receptors. In our study, we investigated the effects of THC on the development of intimal hyperplasia on vessels after angioplasty injury. We used western blot to detect CB1 and CB2 receptors, and observed MAPK signal transduction. Cell proliferation capacity were detected by BrdU incorporation assay. In cell functional assays, we used cell migration assay to observe cell migratory ability in response to THC, CB1 antagonist, and CB2 antagonist. In animal experiments, mice underwent femoral artery wire injury. We used immunofluorescence staining to
detect the expression of CB1 and CB2 receptors on injured vessel. Our data demonstrated that in the course of forming atherosclerosis or restenosis, THC probably promoted the proliferation of the vascular smooth muscle cells（SMCs）, and accelerated the progression of restenosis. This effect of THC could be blocked by CB1 and CB2 antagonists, by suppressing SMCs proliferation. Thus, cannabinoids system maybe a valuable target for attenuating the development of intimal hyperplasia, namely restenosis, after vascular injury.
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