目的:采用脂多糖(LPS)诱导的间质性膀胱炎(IC)动物模型,观察透明质酸(HA)联合表皮生长因子(EGF)膀胱灌注治疗的疗效。
方法:将24只雌性Sprague-Dawley大鼠随机分为4组:假对照,IC,HA,和治疗(HA/EGF)组。将聚乙烯-50管置于每只动物的膀胱内。通过每周两次滴注LPS3周诱导IC,导致尿路上皮的慢性损伤。假手术对照组中的动物仅接受盐水滴注。在IC诱导后第0、7和14天给予HA和HA/EGF的治疗溶液(400μL浓度为0.4mg/0.5mL的HA和400μL的NewEpi,含有2μgEGF和0.4mg透明质酸钠的商业化HA/EGF混合物)。在第21天处死动物用于进一步检查。
结果:与HA组相比,HA/EGF组血尿明显改善,尿中红细胞明显减少。组织学检查显示,HA/EGF治疗逆转了IC中出现的异常,包括炎症细胞的浸润,不规则的上皮再形成,和纤维化组织。此外,HA/EGF显着降低促炎细胞因子(肿瘤坏死因子-α,白细胞介素[IL]-6和IL-1β),并大大降低了升高的氧化应激生物标志物丙二醛,还恢复了抗氧化酶谷胱甘肽过氧化物酶和超氧化物歧化酶的水平,结果优于HA治疗。膀胱测压研究表明,HA/EGF可显着延长收缩间隔并增加排尿量。
结论:HA/EGF已被证明是一种更有效的治疗方法,可以增强尿路上皮衬里并减少炎症变化,以减轻与IC相关的大鼠临床症状。与单独的HA相比。
OBJECTIVE: 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.
CONCLUSIONS: 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.