Changes in smooth muscle cell phenotype and contractile function following ischemia-reperfusion injury in the rat urinary bladder

Abstract

目的:下部尿路閉塞による膀胱機能低下には膀胱虚血・再還流が一要因であるという報告が増加している。今回, ラット膀胱虚血・再還流モデルを用いて膀胱平滑筋細胞における形態学的phenotypeの変化と膀胱機能の関係を検討した。方法:28匹のSD雄ラットを用いて膀胱虚血・再還流(I-R)モデルを作製し, 1時間虚血単独群, 1時間虚血・1時間再還流群, 1時間虚血・4時間再還流群, コントロール群に分類し, 透過型電子顕微鏡による膀胱平滑筋細胞におけるphenotypeの比率および経壁電気刺激とKClに対する等尺性収縮力を測定し, 検討を行った。結果:コントロールにおける膀胱平滑筋細胞の収縮型と非収縮型の比率(nc/c比)は0.169, 虚血単独群はnc/c比は0.991, 1時間I-R群, 4時間I-Rのnc/c比はそれぞれ0.865, 1.601であった。経壁電気刺激とKClに対する等尺性収縮力はI-R群で減少していた。考察:膀胱平滑筋細胞のnc/c比の結果より虚血単独群でも, 非収縮型細胞が増加し, I-Rによりさらに非収縮型細胞が増加することが示された。膀胱平滑筋収縮力は虚血単独群でもI-R群でも減少したが, 収縮反応は膀胱平滑筋細胞のphenotypeの変化とは対応しなかった。(著者抄録)

Twenty-eight adult male Sprague-Dawley rats were divided into four groups: Group 1 received 1 hour (h) of bilateral ischemia alone. Groups 2 and 3 received 1 h ischemia followed by 1 and 4 h of reperfusion (I-R), respectively. Group 4 consisted of age-matched control rats. Bladder strips were studied using electrical field stimulation (EFS) and KCl stimulation. Maximal contractile responses were recorded and analyzed. Temporal patterns of changes in phenotypic (non-contractile and contractile) expression of bladder smooth muscle cells were investigated using electron microscopy. The mean ratio of non-contractile to contractile phenotype (nc/c) of smooth muscle cells (SMCs) in the control group was 0.169. In the ischemia alone group, the ratio was 0.991. In the 1 h I-R group, the ratio 0.865 whereas in 4 h I-R group the ratio 1.601. The contractile responses to EFS and KCl showed decreased responses in all groups. These results clearly demonstrated that the ratio of nc/c increased significantly in the ischemia group and further increased significantly in both I-R groups. The contractile responses decreased in all ischemic groups although the magnitude of the contractile changes did not correspond in the change of phenotype ratio.