Lei Liu, Jie Cui, Wei-Li Qiao, Hong Sun, Chang-Dong Yan, Department of Physiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, China.
World J Gastroenterol. 2013 Dec 28;19(48):9439-46. doi: 10.3748/wjg.v19.i48.9439.
To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.
Twenty male patients undergoing subtotal gastrectomy were enrolled in this study. Young and elderly patient groups aged 25-40 years and 60-85 years, respectively, were included. Inclusion criteria were: no clinical evidence of cardiovascular, renal or diabetic diseases. Conventional clinical examinations were carried out. After surgery, gastric submucosal arteries were immediately dissected free of fat and connective tissue. Vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured by isolated vascular perfusion. Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin (HE) staining and Verhoeff van Gieson (EVG) staining. The expression of xanthine oxidase (XO) and manganese-superoxide dismutase (Mn-SOD) was assessed by Western blotting analysis. The malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined according to commercial kits.
The overall structure of vessel walls was shown by HE and EVG staining, respectively. Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients; however, cell layer number in the vessel wall increased significantly in the elderly group. Compared with submucosal arteries in young patients, the amount of vascular collagen fibers, lumen diameter and media cross-sectional area were significantly increased in elderly patients. Ach- and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients. Compared with the young group, the expression of XO and the contents of MDA and H₂O₂ in gastric submucosal arterioles were increased in the elderly group. In addition, the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group.
Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process.
评估人类胃黏膜下血管功能障碍及其在衰老过程中的机制。
本研究纳入 20 例行胃大部切除术的男性患者。分别纳入年龄在 25-40 岁和 60-85 岁的年轻和老年患者组。纳入标准为:无心血管、肾脏或糖尿病疾病的临床证据。进行常规临床检查。手术后,立即将胃黏膜下动脉从脂肪和结缔组织中分离出来。通过分离血管灌注测量乙酰胆碱(ACh)和硝普钠(SNP)对血管的反应。通过苏木精和伊红(HE)染色和 Verhoeff van Gieson(EVG)染色观察胃黏膜血管的形态变化。通过 Western blot 分析评估黄嘌呤氧化酶(XO)和锰超氧化物歧化酶(Mn-SOD)的表达。根据商业试剂盒测定丙二醛(MDA)和过氧化氢(H₂O₂)含量以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性。
HE 和 EVG 染色分别显示了血管壁的整体结构。年轻或老年患者的血管中未观察到内弹性膜或新生内膜层的破坏;然而,老年组血管壁的细胞层数量显著增加。与年轻患者的胃黏膜下动脉相比,老年患者的血管胶原纤维含量、管腔直径和中膜横截面积显著增加。与年轻患者的胃黏膜下小动脉相比,老年患者的 Ach 和 SNP 诱导的血管舒张明显减少。与年轻组相比,老年组胃黏膜下小动脉中 XO 的表达以及 MDA 和 H₂O₂的含量增加。此外,与年轻组相比,老年组 Mn-SOD 的表达以及 SOD 和 GSH-Px 的活性显著降低。
胃血管功能障碍和衰老可能与衰老过程中氧化应激增加和抗氧化防御减少有关。