オノ　シゲキ   Shigeki Ono   小野　成紀    所属   川崎医科大学  医学部 臨床医学　脳神経外科学２    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Role of extracellular matrix in experimental vasospa sm-Inhibitory effect of antisense oligonucleotide on collagen induction-.
掲載誌名	正式名：Stroke; a journal of cerebral circulation 略　 称：Stroke ISSNコード：00392499/15244628
巻・号・頁	27(11),pp.2102-2109
著者・共著者	Onoda K, Ono S, Ogihara K, Shiota T, Asari S, Ohmoto T, Ninomiya Y.
発行年月	1996/11
概要	Although it has been suggested that collagen plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no constructive research to prove it directly. In this study we stopped the transcription of the procollagen type I gene by introducing antisense oligonucleotides for its mRNA in a rat femoral artery model of vasospasm induced by blood and assayed the changes in the vasoconstrictive activity of the vessel and expression of the procollagen mRNA. We applied antisense, sense, or missense oligonucleotides, located at the carboxyl propeptide region for alpha 1(I) procollagen mRNA, onto the femoral artery in a rat femoral artery model of vasospasm. The diameter of the artery was measured by angiography. The transcription level of the procollagen gene in the arterial tissue was assayed by use of reverse transcription-polymerase chain reaction. Morphological change in the artery was observed with aldehyde-fuchsin-Masson-Goldner staining. In the model, when the artery was exposed to antisense oligonucleotides in pluronic gel for 5 days to prevent arterial contraction, the contraction was inhibited at a significant level (76.0% +/- 5.6) when compared with that in control experiments using sense oligonucleotides (64.0% +/- 2.4), missense oligonucleotides (63.5% +/- 3.5), or gel alone (62.1% +/- 5.8). The application of antisense oligonucleotide resulted in a marked decrease in alpha 1(I) procollagen mRNA expression as determined by polymerase chain reaction, indicating that the collagen reduction by antisense oligonucleotides occurred at the transcription level. Histological staining suggested that collagen accumulation at the site in the artery where antisense oligonucleotide had been administered was indeed less than that in the control artery. The results indicate that the induction of procollagen type 1 could cause pathogenesis of the arterial contraction induced by blood in a rat femoral vasospasm model.
文献番号	8898823