Chih-Chieh Lin, Jenn-Ming Yang, Tzu-Hsiang Hsu, Hua-Lin Lee
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Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations.</p><p><strong>Results: </strong>The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume.</p><p><strong>Conclusion: </strong>HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone.</p>","PeriodicalId":14466,"journal":{"name":"International Neurourology Journal","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222823/pdf/","citationCount":"0","resultStr":"{\"title\":\"Intravesical Instillation of Hyaluronic Acid With Epidermal Growth Factor for Restoring Urothelial Denudation and Alleviating Oxidative Stress in Lipopolysaccharide-Induced Interstitial Cystitis of Rats.\",\"authors\":\"Chih-Chieh Lin, Jenn-Ming Yang, Tzu-Hsiang Hsu, Hua-Lin Lee\",\"doi\":\"10.5213/inj.2448028.014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model.</p><p><strong>Methods: </strong>A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations.</p><p><strong>Results: </strong>The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. 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引用次数: 0
摘要
目的：利用脂多糖（LPS）诱导的间质性膀胱炎动物模型，研究透明质酸（HA）联合表皮生长因子（EGF）膀胱内灌注治疗间质性膀胱炎（IC）的疗效：将 24 只雌性 Sprague-Dawley 大鼠随机分为 4 组：假对照组、IC 组、HA 组和治疗组（HA/EGF）。在每只大鼠的膀胱内放置一根聚乙烯-50管。通过每周两次灌注 LPS 诱导 IC，持续 3 周，导致尿路上皮细胞慢性损伤。假对照组的动物只接受生理盐水灌注。在 IC 诱导后的第 0、7 和 14 天给予 HA 和 HA/EGF 治疗溶液（400 μL 浓度为 0.4 mg/0.5 mL 的 HA 和 400 μL 的 NewEpi，后者是一种商品化的 HA/EGF 混合物，含有 2 μg EGF 和 0.4 mg 透明质酸钠）。动物在第 21 天被处死，以进行进一步检查：与 HA 组相比，HA/EGF 组的血尿症状明显改善，尿液中的红细胞显著减少。组织学检查显示，HA/EGF 治疗逆转了 IC 中出现的异常情况，包括炎症细胞浸润、不规则的再上皮化和纤维组织。此外，HA/EGF还能显著降低促炎细胞因子（肿瘤坏死因子-α、白细胞介素[IL]-6和IL-1β）的水平，大幅降低氧化应激生物标志物丙二醛的升高，恢复抗氧化酶谷胱甘肽过氧化物酶和超氧化物歧化酶的水平，效果优于HA治疗。膀胱测定研究表明，HA/EGF能明显延长收缩间期，增加排尿量：结论：与单独使用 HA 相比，HA/EGF 被证明是一种更有效的治疗方法，可增强尿路上皮内膜，减少炎症变化，从而缓解大鼠 IC 的相关临床症状。
Intravesical Instillation of Hyaluronic Acid With Epidermal Growth Factor for Restoring Urothelial Denudation and Alleviating Oxidative Stress in Lipopolysaccharide-Induced Interstitial Cystitis of Rats.
Purpose: To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model.
Methods: A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations.
Results: The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume.
Conclusion: HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone.
期刊介绍：
The International Neurourology Journal (Int Neurourol J, INJ) is a quarterly international journal that publishes high-quality research papers that provide the most significant and promising achievements in the fields of clinical neurourology and fundamental science. Specifically, fundamental science includes the most influential research papers from all fields of science and technology, revolutionizing what physicians and researchers practicing the art of neurourology worldwide know. Thus, we welcome valuable basic research articles to introduce cutting-edge translational research of fundamental sciences to clinical neurourology. In the editorials, urologists will present their perspectives on these articles. The original mission statement of the INJ was published on October 12, 1997.
INJ provides authors a fast review of their work and makes a decision in an average of three to four weeks of receiving submissions. If accepted, articles are posted online in fully citable form. Supplementary issues will be published interim to quarterlies, as necessary, to fully allow berth to accept and publish relevant articles.
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