增龄通过下调平滑肌细胞BK_(Ca)通道α和β_1亚基表达改变肠系膜动脉舒缩性

Aging Changes the Vascular Contractility in the Rat Mesenteric Arteries by Downregulation of the α-and β_1-subunit Expression of BK_(Ca) Channels in Smooth Muscle Cells

目的探讨增龄对大鼠肠系膜动脉平滑肌细胞大电导钙激活钾通道（BKCa）α和β1亚基蛋白表达的影响。方法选用不同年龄雄性Wistar大鼠,分为青年组（4-5月龄）、中年组（15-16月龄）和老年组（22-24月龄）。分别进行在体血压监测和离体去内皮血管张力测定,并采用蛋白免疫印迹分析观察肠系膜动脉平滑肌细胞BKCa通道α和β1亚基的表达。结果增龄导致大鼠收缩压和脉压显著增大。去甲肾上腺素诱发各组肠系膜动脉收缩,并呈浓度依赖性,增龄导致血管对去甲肾上腺素的敏感性（pD2）和最大收缩反应降低;BKCa通道选择性阻断剂Iberiotoxin诱发各组血管张力增高,但增高幅度青年组〉中年组〉老年组。蛋白免疫印迹分析显示α和β1亚基均随增龄下降,但β1亚基下降幅度显著大于α亚基。结论增龄诱导大鼠肠系膜动脉BKCa通道在血管张力维持中的贡献下降,其分子机制可能为增龄诱发的α和β1亚基表达非平行性下调（β1亚基下调更为显著）。

Aim To investigate the effects of aging on the molecular expression of α-and β1-subunit of largeconductance Ca2 ＋-activated K＋（ BKCa） channels in rat mesenteric arterial smooth muscle cells. Methods Young（ 4~ 5 months）,middle-aged（ 15 ~ 16 months）,and old（ 22 ~ 24 months） male Wistar rats were used. In vivo blood pressure and in vitro endothelium-removed mesenteric arterial tension were measured. Immunohistochemistry and Western Blot assay were also conducted. Results The systolic blood pressure and pulse pressure were significantly increased with aging. The vascular tone caused by norepinephrine（ NE） strongly increased in a concentration dependent manner in each group,and aging reduced the sensitivity to NE in mesenteric arteries（ MA）. Selective BKCachannel blocker（ Iberiotoxin） induced a marked increase of vascular tension in MA in all three age groups. However,these effects were greatly decreased in old animals. Western Blot showed that the protein expression of BKCaα-and β1-subunit was significantly reduced with aging,and the suppression of β1subunits was larger than that of α subunits. Conclusions These data suggest that aging induces decrease of molecular expression of α- and β1-subunit of BKCachannels in MA myocytes,in which the suppression of β1-subunit is more pronounced than α-subunit. This unparallel downregulation of two subunits may be the mechanism underlying the aging-associated decrease of BKCachannel contribution in regulating MA basal tone.