益气固肾汤通过调控TGF-β1/CTGF通路改善压力性尿失禁大鼠阴道损伤及排尿功能障碍

ISSN:2811-051X(P)

EISSN:2811-0781(O)

语言:中文

作者
姜 敏,徐福利,兰叶平
文章摘要
目的:基于转化生长因子-β1(TGF-β1)/结缔组织生长因子(CTGF)通路,探究益气固肾汤对压力性尿失禁(SUI)大鼠盆底损伤及排尿功能的影响。方法:以SD雌性未育大鼠为研究载体,通过模拟产伤联合双侧卵巢切除法建立SUI大鼠模型。随机分为空白对照组、模型组、益气固肾汤低剂量、益气固肾汤中剂量、益气固肾汤高剂量及阳性对照组。各组大鼠给予不同给药处理,给药(28天)结束后进行喷嚏实验及尿流动力学指标检测。采用HE染色和Masson染色观察大鼠阴道组织形态学变化。ELISA检测大鼠阴道组织MDA、总SOD、GSH-Px和CAT水平。TUNEL染色检测盆底肌细胞凋亡水平。PCR检测阴道组织MMPs、TIMPs、TGF-β1及CTGF mRNA表达水平。结果:经益气固肾汤治疗后,SUI大鼠的漏尿点压力(LPP)及腹压漏尿点压力(ALPP)水平增加。HE染色及Masson染色结果显示,益气固肾汤减轻了SUI大鼠阴道组织固有层胶原纤维及肌层平滑肌变细断裂的现象。益气固肾汤提高了SUI大鼠阴道组织SOD、GSH-Px及CAT水平,降低了SUI大鼠阴道组织MDA水平。Tunel染色结果显示,益气固肾汤显著降低SUI大鼠盆底肌细胞凋亡水平。PCR结果中,益气固肾汤组降低SUI大鼠的MMP-2 mRNA表达水平,增加TIMP-2、TGF--β1及CTGF mRNA表达水平。中剂量及高剂量益气固肾汤组相比低剂量组作用效果更好,呈剂量依赖性。结论:益气固肾汤通过调节TGF-β1/CTGF通路抑制ECM降解,同时降低阴道组织氧化应激及凋亡水平,从而改善SUI大鼠的阴道损伤及排尿功能障碍。
文章关键词
压力性尿失禁;益气固肾汤;TGF-β1/CTGF通路;氧化应激
参考文献
[1] Billecocq S,Bo K,Dumoulin C,et al.[An International Urogynecological Association(IUGA)/International Continence Society(ICS)joint report on the terminology for the conservative and non-pharmacological management of female pelvic floor dysfunction][J].Prog Urol,2019,29(4):183-208. [2] Zhang L,Zhu L,Xu T,et al.A Population-based Survey of the Prevalence,Potential Risk Factors,and Symptom-specific Bother of Lower Urinary Tract Symptoms in Adult Chinese Women[J].Eur Urol,2015,68(1):97-112. [3] Morling J R,Mcallister D A,Agur W,et al.Adverse events after first,single,mesh and non-mesh surgical procedures for stress urinary incontinence and pelvic organ prolapse in Scotland,1997-2016:a population-based cohort study[J].Lancet,2017,389(10069):629-640. [4] 杨冬梅,赖登红,曾素娥.益气固肾汤联合盆底肌训练治疗压力性尿失禁 40 例[J].江西中医药,2012,43(05):42-43. [5] 张凯敏,李留霞,袁新枝,等.西洋参总皂苷通过调控 TGF-β1/CTGF 通路对压力性尿失禁大鼠尿道损伤及排尿功能的改善作用研究[J].中医药信息,2022,39(06):22-27. [6] 祖宁辉,施田力,黄小惠,等.木黄酮对卵巢切除压力性尿失禁大鼠模型的影响[J].中国临床药理学杂志,2020,36(10):1318-1320. [7] 袁夺,李小丽.女性压力性尿失禁的治疗新进展[J].中国计划生育和妇产科,2022,14(09):6-9. [8] Moser H,Leitner M,Baeyens J P,et al.Pelvic floor muscle activity during impact activities in continent and incontinent women:a systematic review[J].Int Urogynecol J,2018,29(2):179-196. [9] Koike Y,Furuta A,Suzuki Y,et al.Pathophysiology of urinary incontinence in murine models[J].Int J Urol,2013,20(1):64-71. [10] Blomquist J L,Carroll M,Munoz A,et al.Pelvic floor muscle strength and the incidence of pelvic floor disorders after vaginal and cesarean delivery[J].Am J Obstet Gynecol,2020,222(1):61-62. [11] Rynkevic R,Martins P,Andre A,et al.The effect of consecutive pregnancies on the ovine pelvic soft tissues:Link between biomechanical and histological components[J].Ann Anat,2019,222:166-172. [12] Tang J,Li B,Liu C,et al.Mechanism of Mechanical Trauma-Induced Extracellular Matrix Remodeling of Fibroblasts in Association with Nrf2/ARE Signaling Suppression Mediating TGF-beta1/Smad3 Signaling Inhibition[J].Oxid Med Cell Longev,2017,2017:8524353. [13] Hong S,Hong L,Li B,et al.The role of GPX1 in the pathogenesis of female pelvic organ prolapse[J].PLoS One,2017,12(8):e181896. [14] 汤剑明.Nrf2 在机械损伤所致压力性尿失禁小鼠盆底组织修复中的作用及机制[D].武汉大学,2019. [15] 李文婷,李淑萍,王英红.多模式综合疗法对老年轻中度盆腔器官脱垂患者盆底肌力及血清 SOD、GSH-Px 含量的影响[J].中国老年学杂志,2019,39(17):4246-4250. [16] Strasser H,Tiefenthaler M,Steinlechner M,et al.Age dependent apoptosis and loss of rhabdosphincter cells[J].J Urol,2000,164(5):1781-1785. [17] Kim E J,Chung N,Park S H,et al.Involvement of oxidative stress and mitochondrial apoptosis in the pathogenesis of pelvic organ prolapse[J].J Urol,2013,189(2):588-594. [18] Vasin R V,Filimonov V B,Mnikhovich M V,et al.[Morphologic structure and immunohistochemical analysis of vaginal wall in women with pelvic organ prolapse][J].Urologiia,2019(6):12-20. [19] 王鸿,齐振阳,王建.塞来昔布对压力性尿失禁模型大鼠的效果及作用机制[J].现代泌尿外科杂志,2020,25(01):68-71. [20] 左晓虎,洪莉.压力性尿失禁发病机制研究进展[J].现代妇产科进展,2021,30(03):217-220. [21] Cao Z,Liu W,Qu X,et al.miR-296-5p inhibits IL-1beta-induced apoptosis and cartilage degradation in human chondrocytes by directly targeting TGF-beta1/CTGF/p38MAPK pathway[J].Cell Cycle,2020,19(12):1443-1453. [22] Han K,Zhang Y,Yang Z.Cilostazol protects rats against alcohol-induced hepatic fibrosis via suppression of TGF-beta1/CTGF activation and the cAMP/Epac1 pathway[J].Exp Ther Med,2019,17(3):2381-2388.
Full Text:
DOI