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首页> 外文期刊>Journal of Surgical Research: Clinical and Laboratory Investigation >Epigallocatechin gallate attenuates interstitial cystitis in human bladder urothelium cells by modulating purinergic receptors
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Epigallocatechin gallate attenuates interstitial cystitis in human bladder urothelium cells by modulating purinergic receptors

机译：表没食子儿茶素没食子酸酯通过调节嘌呤能受体减轻人膀胱尿路上皮细胞的间质性膀胱炎

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Background: Epigallocatechin gallate (EGCG) has exhibited antitumor properties against bladder cancer. However, its effects in interstitial cystitis (IC) have not been investigated. Methods: Here, we performed repeated cystoscopy and re-biopsy of bladder mucosa before and after intravesical irrigation of EGCG in eight patients diagnosed with IC based on clinical and histopathologic assessments. Six normal bladder tissue samples were obtained from age-, race-, and sex-matched asymptomatic control subjects. IC symptom index was used to compare the therapeutic effect in IC patients. Patient-derived bladder epithelial cells were cultured and cell stretch experiments and ATP assays were performed. The expression of purinergic receptors X1, X2, and X3, and Y1, Y2, and Y 11, in biopsied samples was detected by Western blotting and real-time polymerase chain reaction, respectively. Moreover, the expression of inducible NO synthase, phosphorylated Akt, and phosphorylated NF-κB was also assessed. Results: All EGCG-treated patients demonstrated different extents of remission of symptoms. We found a significant upregulation in P2X 1, P2X2, and P2X3 receptor proteins and P2Y1, P2Y2, and P2Y11 receptor transcripts in IC patients. However, EGCG therapy attenuated the expression of all purinergic receptors. In addition, EGCG demonstrated prominent antioxidative and antiinflammatory effects via inhibition of the upregulation of iNOS and phosphorylated NF-κB. Furthermore, the stretch-activated release of ATP in cultured bladder urothelial cells was greater in cells derived from IC patients, compared with those from the control patients, but EGCG, at all concentrations tested, effectively abolished the increase in ATP release from stretched IC patient-derived cells. Conclusions: Our study suggests that inhibition of the expression of purinergic receptors and ATP release in urothelial cells by EGCG supports further development of EGCG as a novel therapeutic option for IC.
机译：背景：表没食子儿茶素没食子酸酯（EGCG）已显示出抗膀胱癌的抗肿瘤特性。但是，尚未研究其在间质性膀胱炎（IC）中的作用。方法：根据临床和组织病理学评估，我们对8例经诊断为IC的IC患者行EGCG膀胱冲洗前后，进行了膀胱镜检查和膀胱黏膜再活检。从年龄，种族和性别匹配的无症状对照受试者中获得六个正常膀胱组织样品。 IC症状指数用来比较IC患者的治疗效果。培养患者来源的膀胱上皮细胞，并进行细胞拉伸实验和ATP测定。分别通过蛋白质印迹和实时聚合酶链反应检测活检样品中嘌呤能受体X1，X2和X3以及Y1，Y2和Y 11的表达。此外，还评估了诱导型NO合酶，磷酸化的Akt和磷酸化的NF-κB的表达。结果：所有EGCG治疗的患者均表现出不同程度的症状缓解。我们发现IC患者的P2X 1，P2X2和P2X3受体蛋白以及P2Y1，P2Y2和P2Y11受体转录显着上调。但是，EGCG治疗减弱了所有嘌呤能受体的表达。此外，EGCG通过抑制iNOS和磷酸化的NF-κB的上调显示出显着的抗氧化和抗炎作用。此外，与对照患者相比，IC患者来源的细胞中培养的膀胱尿路上皮细胞中ATP的拉伸激活释放更大，但是在所有测试浓度下，EGCG有效地消除了舒张IC患者中ATP释放的增加来源的细胞。结论：我们的研究表明，EGCG抑制尿路上皮细胞中嘌呤能受体的表达和ATP释放支持EGCG的进一步发展，将其作为IC的新型治疗选择。

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