高压氧对输尿管梗阻大鼠的肾病理组织及氧化应激损伤的作用机制  

Mechanism of hyperbaric oxygen on renal tissue and oxidative stress injury in rats with ureteral obstruction

作　　者：周燕 雷佳玉 谢艳 Zhou Yan;Lei Jiayu;Xie Yan(Department of Minimally Invasive Surgery,the Fourth Hospital of West China,Sichuan University,Chengdu 610000,China)

机构地区：[1]四川大学华西第四医院微创外科,成都610000

出　　处：《国际泌尿系统杂志》2025年第1期107-112,共6页International Journal of Urology and Nephrology

基　　金：四川省卫生健康委医学科学基金资助项目(19PJ228)。

摘　　要：目的探讨高压氧对输尿管结扎术后梗阻大鼠的肾病理组织及氧化应激损伤的作用机制。方法选取40只SPF级SD雄性大鼠,随机将大鼠分为正常组(N组)、模型组(M组)、高压氧(O组)、血管内皮生长因子(VEGF)抑制剂+高压氧组(V组),每组10只。对M、O、V组大鼠采用输尿管结扎法进行输尿管梗阻建模,N组不建立该模型,当大鼠出现精神萎靡、形体瘦弱、粪便时软或不成形等现象时,则视为建模成功。建模成功后,O组进行高压氧治疗,V组腹腔注射13.5 mg/kg VEGF抑制剂后进行高压氧治疗,N组、M组同期给予腹腔注射同体积生理盐水。采用HE染色及Masson染色检测各组肾组织的损伤情况,采用ELISA法检测各组的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)等氧化应激相关指标,采用免疫印迹法检测各组的VEGF、血管内皮生长因子受体2(VEGFR2)蛋白表达。取对数生长的肾小管上皮细胞,将其分为A组(给予高压空气)和B组(给予高压氧),采用免疫印迹法检测VEGF、VEGFR2蛋白表达验证高压氧对VGEF信号通路的作用。结果N组肾组织结构、肾小球、肾小管形态正常且排列整齐,M组肾小管可见空泡样变性和明显皮质扩张,肾小管上皮细胞出现片状萎缩、脱落和坏死,且可见大量炎性细胞浸润及明显肾间质纤维化,与M组相比,O组、V组的病理形态明显改善。N组、M组、O组、V组的肾间质纤维化面积分别为(4.26±1.21)%、(39.66±3.67)%、(8.75±1.88)%、(28.44±2.91)%,差异有统计学意义(F=411.700,P<0.001)。与N组比较,M组血清中SOD、GSH-Px、VEGF、VEGFR2蛋白表达水平降低,MDA升高(均P<0.05)。与M组比较,O组血清中SOD、GSH-Px、VEGF、VEGFR2蛋白表达水平升高,MDA降低(均P<0.05)。与O组相比,V组血清中SOD、GSH-Px、VEGF、VEGFR2蛋白表达水平降低,MDA升高(均P<0.05)。与A组比较,B组肾小管上皮细胞中VEGF、VEGFR2蛋白表达升高(均P<0.05)。结论Objective To explore the mechanism of hyperbaric oxygen on pathological renal tissue and oxidative stress injury in rats with ureteral ligation obstruction.Methods Forty SPF grade SD male rats were selected and randomly divided into normal group(group N),model group(group M),hyperbaric oxygen(group O),vascular endothelial growth factor(VEGF)inhibitor+hyperbaric oxygen group(group V),with 10 rats in each group.Ureteral obstruction modeling was performed by ureteral ligation in groups M,O and V,while the model was not established in group N,and the modeling was considered successful when mental drowsiness,emaciation,and soft or shaptless feces appeared in rats.After successful modeling,group O was given hyperbaric oxygen therapy,group V was given hyperbaric oxygen therapy after intraperitoneal injection of 13.5 mg/kg VEGF inhibitor,and group N and group M were given intraperitoneal injection of the same volume of normal saline at the same time.HE staining and Masson staining were used to detect the renal tissue damage in each group,the oxidative stress related indexes of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in each group were detected by ELISA,and the protein expressions of VEGF and vascular endothelial growth factor receptor 2(VEGFR2)in each group were detected by Western blot.Logarithmic growth of renal tubular epithelial cells was divided into group A(given high-pressure air)and group B(given hyperbaric oxygen).Western blot was used to detect the expression of VEGF and VEGFR2 proteins to verify the effect of hyperbaric oxygen on VGEF signaling pathway.Results Compared with group M,the pathological morphology of group O and group V was significantly improved.The area of renal interstitial fibrosis in groups N,M,O and V was(4.26±1.21)%,(39.66±3.67)%,(8.75±1.88)%and(28.44±2.91)%,respectively,and the differences were statistically significant(F=411.700,P<0.001).Compared with group N,the protein expression levels of SOD,GSH-Px,VEGF and VEGFR2 in serum of group M were dec

关 键 词：输尿管梗阻 动物实验 大鼠 高压氧 氧化应激 

分 类 号：R692[医药卫生—泌尿科学] R-332[医药卫生—外科学]