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目的探讨替米沙坦对4%高盐诱导Wistar大鼠肠系膜动脉重构中血管平滑肌细胞(VSMC)表型转化的影响。方法将雄性Wistar大鼠按随机原则分为对照组(0.5%NaCl饲料饲养)、模型组(4%NaCl饲料饲养)、替米沙坦组[4%NaCl饲料+替米沙坦5mg/(kg·d)],共喂养24周。运用HE、Masson及免疫组织化学染色观察肠系膜动脉结构变化。实时荧光定量聚合酶链反应(PCR)及Western blot检测肠系膜动脉平滑肌肌动蛋白(SMA)、平滑肌22α(SM22α)、调宁蛋白(calponin)和骨桥蛋白(OPN)的mRNA和蛋白表达水平。结果与对照组(n=8)比较,模型组(n=10)血压升高,肠系膜动脉中膜增厚,中膜厚度/腔径、血管壁横截面积、血管壁横截面积/腔径和中膜胶原容积分数增加,增殖细胞核抗原(PCNA)阳性表达率增加(0.612±0.096比0.184±0.041,P<0.01),SMA、SM22α、调宁蛋白的mRNA和蛋白表达降低,而骨桥蛋白的mRNA和蛋白表达升高;与模型组相比,替米沙坦组(n=9)血压降低,肠系膜动脉中膜厚度和中膜厚度/腔径、血管壁横截面积、血管壁横截面积/腔径减小,中膜胶原容积分数降低,PCNA阳性表达率减少(0.208±0.029比0.612±0.096,P<0.01),SMA、SM22α、调宁蛋白的mRNA及蛋白表达升高,而骨桥蛋白的mRNA及蛋白表达降低。结论 4%高盐喂食可引起Wistar大鼠肠系膜动脉重构和血压升高,VSMC由收缩型向合成型转化可能是其机制之一;替米沙坦可能通过逆转VSMC表型转化,改善肠系膜动脉重构。
Objective To investigate the effect of telmisartan on the phenotype of vascular smooth muscle cells (VSMCs) in 4% high-salt induced Wistar rat mesenteric artery remodeling. Methods Male Wistar rats were randomly divided into control group (0.5% NaCl feeding), model group (4% NaCl feeding), telmisartan group [4% NaCl feeding + D)] for a total of 24 weeks. The structure of mesenteric artery was observed by HE, Masson and immunohistochemical staining. The mRNA and protein expression of SMA, SM22α, calponin and osteopontin (OPN) of mesenteric artery were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) and Western blot. Results Compared with the control group (n = 8), the model group (n = 10) had elevated blood pressure, thickening of mesenteric artery medial membrane, thickness of medial membrane / lumen, cross-sectional area of blood vessel wall, (P <0.01). The positive expression rate of PCNA increased (0.612 ± 0.096 vs 0.184 ± 0.041, P <0.01), and the mRNA and protein expression of SMA, SM22α and tonotin decreased, while the expression of osteopontin (N = 9) decreased blood pressure, mesenteric artery intima-media thickness and media thickness / lumen diameter, blood vessel wall cross-sectional area, blood vessel wall cross-section (P <0.01). The expression of SMA, SM22α and tonotin mRNA and protein were increased while the ratio of PCNA positive expression was decreased (0.208 ± 0.029 vs 0.612 ± 0.096, P <0.01) Bridge protein mRNA and protein expression decreased. Conclusions 4% high-salt diet may induce remodeling of mesenteric artery and increase of blood pressure in Wistar rats. One of the mechanisms may be the conversion of VSMC from contractile to synthetic. Telmisartan may improve mesenteric artery by reversing VSMC phenotype Reconstruction.