背景:尿路感染(UTI)是全球流行的传染病,主要由尿路致病性大肠杆菌(UPEC)引起。抗生素的滥用导致了几种耐药菌株的出现。中医药在治疗尿路感染方面有其自身的优势。HJ颗粒是用于治疗UTI的草药配方。然而,其作用机制尚不清楚。
目的:研究HJ颗粒对大肠杆菌(Ecoli)CFT073所致UTI大鼠模型的治疗效果及作用机制。
方法:选用SD大鼠,采用经尿道放置法膀胱内注射UPEC菌株CFT073建立大鼠UTI模型。造模后对大鼠给予HJ颗粒,并通过测量尿去类似物来研究HJ颗粒的功效。给药3d后膀胱组织炎症因子和膀胱病理变化。声音刺猬(SHH)的表达,NOD样受体热蛋白结构域3(NLRP3),通过蛋白质印迹和免疫荧光染色在大鼠膀胱组织中检测到凋亡相关的斑点样蛋白(ASC)和半胱氨酰天冬氨酸特异性蛋白酶-1(caspase-1)的激活。NLRP3,ASC和caspase-1,一种含半胱氨酸的天冬氨酸,被表达和激活。
结果:结果表明,UPEC感染大鼠导致膀胱冲洗液中pH和红细胞升高;IL-1β表达增加,IL-6和SHH降低了膀胱组织中IL-10的表达;SHH和NLRP3炎症的表达均显着上调,NLRP3炎症的显着激活。HJ颗粒显著增加膀胱中IL-10的浓度,抑制膀胱组织中SHH和NLRP3炎症的表达,抑制了NLRP3炎症的激活,从而减少膀胱组织的炎性病变。
结论:HJ颗粒可能通过抑制NLRP3炎症因子的表达和激活来改善膀胱损伤和治疗UTI。
BACKGROUND: Urinary tract infections (UTIs) are globally prevalent infectious diseases, predominantly caused by uropathogenic Escherichia coli (UPEC). The misuse of antibiotics has led to the emergence of several drug-resistant strains. Traditional Chinese Medicine (TCM) has its own advantages in the treatment of UTIs. HJ granules is a herbal formula used for the treatment of UTIs. However, its mechanism of action is not clear.
OBJECTIVE: The aim of this study was to investigate the therapeutic efficacy and mechanism of action of HJ granules in a rat model of UTI caused by Escherichia coli (E coli) CFT073.
METHODS: SD rats were selected to establish a rat UTI model by injecting UPEC strain CFT073 into the bladder using the transurethral placement method. HJ granules were administered to rats after modelling and the efficacy of HJ granule was investigated by measuring urinary decanalogue, inflammatory factors in bladder tissue and pathological changes in the bladder after 3d of administration. Expression of sonic hedgehog (SHH), NOD-like receptor thermoprotein domain 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and activation of cysteinyl aspartate specific proteinase-1 (caspase-1) were detected by western blotting and immunofluorescence staining in rat bladder tissue. NLRP3, ASC and caspase-1, a cysteine-containing aspartic protein, were expressed and activated.
RESULTS: The results showed that infection of rats with UPEC resulted in increased pH and erythrocytes in bladder irrigation fluid; increased expression of IL-1β, IL-6 and SHH and decreased expression of IL-10 in bladder tissue; and significant upregulation of the expression of both SHH and NLRP3 inflammasom and significant activation of NLRP3 inflammasom. HJ granules significantly increased the concentration of IL-10 in the bladder, inhibited the expression of SHH and NLRP3 inflammasom in bladder tissue, and suppressed the activation of NLRP3 inflammasom, thereby reducing inflammatory lesions in bladder tissue.
CONCLUSIONS: HJ granules may improve bladder injury and treat UTIs by inhibiting the expression and activation of NLRP3 inflammasom.