Wang Guang, Li Pei, Su Si-Wei, Xu Rui, Huang Zi-Ye, Yang Tong-Xin, Li Jiong-Ming
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
Aging (Albany NY). 2024 Mar 22;16(7):5949-5966. doi: 10.18632/aging.205682.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats.
LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats.
QCT treatment significantly decreased the level of MPO, IL-1β, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1β, IL-6 and TNF-α.
In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.
间质性膀胱炎/膀胱疼痛综合征(IC/BPS)是一种伴有膀胱疼痛的慢性疾病。目前,IC/BPS的发病机制仍不清楚。槲皮素(QCT)是一种来源广泛且具有多种生物活性的天然黄酮类化合物。本研究旨在探讨QCT对IC模型大鼠mRNA表达及相关调控信号通路的影响。
采用LL-37诱导IC/BPS模型大鼠。将20mg/kg QCT腹腔注射到IC/BPS大鼠体内。采用ELISA、HE、Masson和TB染色评估炎症水平和病理情况。用HPLC检测大鼠体内QCT的浓度。采用mRNA测序检测各组差异表达(DE)mRNA。在IC/BPS模型大鼠中进行Lpl的过表达实验。
QCT治疗显著降低了LL-37诱导的大鼠体内MPO、IL-1β、IL-6和TNF-α的水平,减轻了膀胱损伤和肥大细胞脱颗粒。各组间mRNA测序数据存在显著差异,通过Cytohubba筛选出枢纽基因Lpl。Lpl在IC/BPS大鼠中的表达下调。QCT干预促进了Lpl的表达。Lpl过表达减轻了LL-37诱导的膀胱损伤,增加了糖胺聚糖(GAG)水平,降低了MPO、IL-1β、IL-6和TNF-α的表达。
在本研究中,我们提供了QCT治疗的IC/BPS大鼠的DE mRNA、DE富集的信号通路,筛选出枢纽基因,并揭示Lpl过表达减轻了IC/BPS模型大鼠的症状。