本文旨在观察亚急性衰老大鼠血管壁结构和功能的改变,探讨硫化氢(hydrogen sulfide,H2S)对血管老化的影响。雄性SD大鼠40只,随机分为溶剂组、D-半乳糖组、NaHS(H2S的供体)低、中、高剂量组,每组8只。D-半乳糖组每日背部皮下注射125 mg/kg D-半乳糖,连续8周;溶剂组每日背部皮下注射等体积生理盐水;NaHS低、中、高剂量组每日背部皮下注射125 mg/kg D-半乳糖,同时分别按1、10、100μmol/kg腹腔注射NaHS,连续8周。HE和Masson染色法观察各组大鼠主动脉形态学改变;硫代巴比妥酸(TBA)法和黄嘌呤氧化酶法检测大鼠主动脉超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量以及抗超氧阴离子含量;生化方法测定大鼠血清H2S浓度的变化;酶联免疫法(ELISA)检测血浆血管紧张素II(AngII)浓度变化;免疫印迹法测定大鼠主动脉血管紧张素II型1类受体(AT1R)蛋白的表达。结果显示,与溶剂组相比,D-半乳糖组大鼠血清H2S的浓度降低(P<0.05);而给予NaHS处理后,NaHS各剂量组大鼠血清H2S的浓度较D-半乳糖组明显升高(P<0.05)。血清H2S浓度的增高能够改善D-半乳糖引起的亚急性衰老大鼠主动脉形态学的变化。HE染色结果中,溶剂组主动脉内膜较薄,结构完整,中膜平滑肌排列规则;D-半乳糖组主动脉内膜增厚、隆起,内皮细胞部分脱落,中膜明显增厚,平滑肌增生、紊乱;与D-半乳糖组相比,NaHS各剂量组内皮细胞脱落减少,平滑肌细胞增生减少。Masson染色结果表明:与溶剂组相比,D-半乳糖组胶原纤维增多,平滑肌细胞增生(P<0.05);与D-半乳糖组相比,NaHS各剂量组胶原纤维减少,平滑肌细胞增生减少(P<0.05)。ELISA检测结果显示:与溶剂组相比,D-半乳糖组大鼠血浆AngII浓度明显升高(P<0.05);而给予NaHS处理后,NaHS各剂量组大鼠血浆AngII浓度较D-半乳糖组明显降低(P<0.05)。与溶剂组相比,D-半乳糖组大鼠主动脉SOD活性下降、MDA含量升高、抗超氧阴离子含量降低(P<0.05);而给予NaHS处理后,血管组织氧化应激水平得到明显改善:与D-半乳糖组相比,NaHS各剂量组主动脉SOD活性升高、MDA含量降低、抗超氧阴离子含量升高(P<0.05)。免疫印迹法测定显示,与溶剂组相比,D-半乳糖组大鼠主动脉血管AT1R蛋白表达上调(P<0.05),给予NaHS处理能下调主动脉AT1R蛋白的表达。以上结果提示,外源性H2S能够改善亚急性衰老大鼠主动脉形态学变化,降低血浆AngII的浓度、下调主动脉AT1R蛋白的表达,提高血管组织抗氧化应激的能力,延缓血管老化的发生。 This article aims to observe the changes of the structure and function of the vascular wall in subacute aging rats and to explore the effect of hydrogen sulfide (H2S) on the aging of blood vessels. Forty male SD rats were randomly divided into solvent group, D-galactose group, NaHS (donor of H2S) low, medium and high dose group, 8 rats in each group. The D-galactose group was injected subcutaneously with 125 mg / kg D-galactose every day for 8 weeks. The rats in the solvent group were injected subcutaneously with the same volume of normal saline on the back. The NaHS low, medium and high dose groups were injected subcutaneously with 125 mg / kg D-galactose, meanwhile, NaHS was injected intraperitoneally at 1, 10 and 100μmol / kg for 8 weeks. Morphological changes of the aorta were observed by HE and Masson staining. The activity of superoxide dismutase (SOD) in the aorta was detected by thiobarbituric acid (TBA) and xanthine oxidase (MDA) and anti-superoxide anion content were measured by enzyme-linked immunosorbent assay (ELISA). The changes of serum H2S concentrations were measured by biochemical methods. The concentrations of plasma angiotensin II (AngII) were detected by enzyme-linked immunosorbent assay Expression of Type II Receptor Type 1 Receptor (AT1R) Protein. The results showed that compared with the solvent group, the concentration of H2S in the serum of the D-galactose group decreased (P <0.05), while the concentration of NaHS in the NaHS group was significantly higher than that of the D-galactose group Increased (P <0.05). The increase of serum H2S concentration can improve the morphological changes of aorta in D-galactose-induced subacute aging rats. In the HE staining results, the aortic intima in the solvent group was thinner, the structure was complete, and the smooth muscle in the tunica media arranged regularly. The aorta in the D-galactose group had thickening and bulging intima, partial detachment of endothelial cells, thickening of the tunica media and smooth muscle hyperplasia , Disorder; compared with the D-galactose group, NaHS dose groups of endothelial cells shedding decreased smooth muscle cell proliferation decreased. The results of Masson staining showed that compared with the solvent group, collagen fibers increased and smooth muscle cells proliferated in D-galactose group (P <0.05). Compared with D-galactose group, the collagen fibers in each dose of NaHS decreased and the proliferation of smooth muscle cells decreased (P <0.05). Compared with the solvent group, the concentration of AngII in plasma in D-galactose group was significantly higher than that in the solvent group (P <0.05); while the concentration of NaII in NaHS group was significantly higher than that of D-galactose group Group was significantly lower (P <0.05). Compared with the solvent group, the activity of SOD in the aorta of D-galactose-treated rats decreased, the content of MDA increased and the content of anti-superoxide anion decreased (P <0.05), while the level of oxidative stress in the vascular tissue was significantly increased Improvement: Compared with D-galactose group, SOD activity, MDA content and superoxide anion content in the aorta of NaHS groups increased (P <0.05). Western blotting showed that compared with the solvent group, the expression of AT1R protein in the aorta of D-galactose group was up-regulated (P <0.05), NaHS treatment could down-regulate the expression of AT1R protein in the aorta. The above results suggest that exogenous H2S can improve the morphological changes of aorta in subacute aging rats, decrease the concentration of plasma AngII, down-regulate the expression of AT1R protein in the aorta, increase the anti-oxidative stress ability of vascular tissue and delay the occurrence of vascular aging .