Zhang Hengshuai, Zhao Jiang, Lu Qudong, Sun Bishao, Liu Xin, Yang Chengfei, Li Shuai, Li Longkun, Yi Shanhong, Yang Zhenxing, Xu Jie
Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Evid Based Complement Alternat Med. 2021 Nov 11;2021:1718709. doi: 10.1155/2021/1718709. eCollection 2021.
Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. This study aims to explore the protective effect of LUT on CYP-induced acute cystitis in rats. Female Sprague-Dawley rats were randomly assigned to the control (CON) group, CON + LUT group, CYP group, and CYP + LUT group. A single intraperitoneal injection of CYP was administered to establish an acute hemorrhagic cystitis model. HE staining was performed to detect the degree of bladder tissue damage, and TUNEL staining was performed to count apoptotic cells. Oxidative stress indicators were measured using commercial kits, and bladder surgery was performed to assess urinary function. The levels of inflammatory cytokines, apoptosis-related indicators, TXNIP/NLRP3 pathway, and NF-B pathway were detected by western blot. We found that LUT treatment reduced bladder bleeding, congestion, and edema caused by CYP. Compared with the CYP + LUT group, the level of apoptosis was more highly expressed in the CYP group. We also found that caspase-3, caspase-8, and Bax were significantly upregulated and Bcl-2 was downregulated after LUT treatment. In addition, LUT inhibited the activation of NF-B signal pathway in the rat bladder tissue after CYP exposure. LUT treatment can also reduce the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and TXNIP in the bladder. Finally, LUT can reduce the increase in the urination frequency and maximum urination pressure caused by cystitis. These results indicate that LUT displays effective anti-inflammatory, antioxidant, and antiapoptotic properties in CYP-induced acute hemorrhagic cystitis rats by inhibiting the TXNIP/NLRP3 and NF-B pathways. LUT may be a potent therapeutic agent for the prevention and treatment of hemorrhagic cystitis.
出血性膀胱炎是环磷酰胺化疗的一种重要并发症，目前针对该疾病的治疗方法有限。天然黄酮类化合物木犀草素（LUT）具有显著的抗炎和抗氧化特性，但其对环磷酰胺（CYP）诱导的膀胱毒性的保护作用尚未得到评估。本研究旨在探讨LUT对CYP诱导的大鼠急性膀胱炎的保护作用。将雌性Sprague-Dawley大鼠随机分为对照组（CON）、CON + LUT组、CYP组和CYP + LUT组。单次腹腔注射CYP以建立急性出血性膀胱炎模型。进行HE染色以检测膀胱组织损伤程度，进行TUNEL染色以计数凋亡细胞。使用商业试剂盒测量氧化应激指标，并进行膀胱手术以评估排尿功能。通过蛋白质免疫印迹法检测炎症细胞因子、凋亡相关指标、TXNIP/NLRP3途径和NF-κB途径的水平。我们发现LUT治疗减少了CYP引起的膀胱出血、充血和水肿。与CYP + LUT组相比，CYP组的凋亡水平表达更高。我们还发现LUT治疗后caspase-3、caspase-8和Bax显著上调，而Bcl-2下调。此外，LUT抑制了CYP暴露后大鼠膀胱组织中NF-κB信号通路的激活。LUT治疗还可降低膀胱中NLRP3炎性小体（NLRP3、ASC和caspase-1）和TXNIP的水平。最后，LUT可降低膀胱炎引起的排尿频率增加和最大排尿压力。这些结果表明，LUT通过抑制TXNIP/NLRP3和NF-κB途径，在CYP诱导的急性出血性膀胱炎大鼠中表现出有效的抗炎、抗氧化和抗凋亡特性。LUT可能是预防和治疗出血性膀胱炎的一种有效治疗剂。
