School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China.
Shanxi Key Laboratory of Chronic Inflammatory Targeted Drugs, School of Traditional Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China.
Int Immunopharmacol. 2018 Sep;62:155-164. doi: 10.1016/j.intimp.2018.07.001. Epub 2018 Jul 11.
Antibiotics are still the primary therapy for acute pyelonephritis (APN); rarely, natural polyphenols are also used. LM49 is a novel marine bromophenol derivative displaying strong anti-inflammatory effects. We investigated the therapeutic efficacy of LM49 in an experimental rat model of APN. The model was established by injecting 0.5 mL Escherichia coli (ATCC 25922, 10 CFU/mL) into the urinary bladders of Sprague Dawley rats. This model showed increased kidney viscera indices and renal bacterial growth scores, as well as pathological changes in kidneys. We also performed a broth microdilution antimicrobial susceptibility test of the E. coli strain. Both norfloxacin and LM49 treatment reduced kidney viscera indices and decreased microbial counts in urine cultures and kidney homogenates in APN rats. However, in vitro experiments showed that LM49 did not directly inhibit bacteria. Rather, LM49 treatment inhibited inflammatory cell infiltration or abscess and improved tissue lesions in the renal medullary junction, renal pelvis, and calyx, and high-dose LM49 treatment inhibited the production of inflammatory interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum. CD4 T cells were higher in the LM49 groups treated with high, medium, and low doses than in the model group, whereas only high-dose LM49 treatment increased the number of CD8 T cells, as compared with that in the model group. However, LM49 treatment did not influence hematological parameters. Our results show that LM49 therapeutic effects in an APN animal model may be achieved by regulating immune responses and inhibiting inflammatory mediators, suggesting it as a candidate APN treatment.
抗生素仍然是急性肾盂肾炎 (APN) 的主要治疗方法；很少使用天然多酚。LM49 是一种新型海洋溴酚衍生物，具有很强的抗炎作用。我们研究了 LM49 在 APN 实验大鼠模型中的治疗效果。该模型通过向 Sprague Dawley 大鼠的膀胱内注射 0.5 mL 大肠杆菌 (ATCC 25922，10 CFU/mL) 建立。该模型显示肾脏内脏指数增加和肾脏细菌生长评分升高，以及肾脏的病理变化。我们还对大肠杆菌菌株进行了肉汤微量稀释抗菌药敏试验。诺氟沙星和 LM49 治疗均降低了 APN 大鼠的肾脏内脏指数，并减少了尿液培养物和肾脏匀浆中的微生物计数。然而，体外实验表明 LM49 不能直接抑制细菌。相反，LM49 治疗抑制了炎症细胞浸润或脓肿，并改善了肾髓质集合管、肾盂和肾盏的组织损伤，高剂量 LM49 治疗抑制了血清中炎症白细胞介素-1β (IL-1β) 和白细胞介素-6 (IL-6) 的产生。与模型组相比，高、中、低剂量 LM49 治疗组的 CD4 T 细胞更高，而只有高剂量 LM49 治疗组增加了 CD8 T 细胞的数量，与模型组相比。然而，LM49 治疗并未影响血液学参数。我们的结果表明，LM49 在 APN 动物模型中的治疗效果可能是通过调节免疫反应和抑制炎症介质来实现的，这表明它可能是 APN 的一种治疗选择。
