当前位置: X-MOL 学术Int. Immunopharmacol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Therapeutic effects of 5,2′-dibromo-2,4′,5′-trihydroxydiphenylmethanone (LM49) in an experimental rat model of acute pyelonephritis by immunomodulation and anti-inflammation
International Immunopharmacology ( IF 4.8 ) Pub Date : 2018-07-11 , DOI: 10.1016/j.intimp.2018.07.001
Yuan Lin Zhang , Xiu E. Feng , Rong Rong Chang , Le Hua Zhang , Bao Guo Xiao , Qing Shan Li , Xu Liang Hao

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, 108 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.



中文翻译:

5,2'-dibromo-2,4',5'-三羟基二苯甲酮(LM49)通过免疫调节和抗炎作用在急性肾盂肾炎实验大鼠模型中的治疗作用

抗生素仍然是急性肾盂肾炎(APN)的主要疗法。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。我们在APN的实验大鼠模型中研究了LM49的治疗功效。通过将0.5 mL大肠杆菌(ATCC 25922,10 8  CFU / mL)注入Sprague Dawley大鼠的膀胱中来建立模型。该模型显示出肾脏内脏指数和肾脏细菌生长分数增加,以及肾脏的病理变化。我们还对大肠杆菌进行了肉汤微稀释抗药性试验应变。诺氟沙星和LM49治疗均降低了APN大鼠尿液培养物中的肾脏内脏指数并减少了微生物计数和肾脏匀浆中的微生物数量。但是,体外实验表明LM49不能直接抑制细菌。相反,LM49治疗可抑制炎性细胞浸润或脓肿,并改善肾髓交界处,肾盂和萼中的组织损伤,大剂量LM49治疗可抑制炎性白介素-1β(IL-1β)和白介素-6( IL-6)在血清中。高,中,低剂量治疗的LM49组的CD4 + T细胞高于模型组,而仅大剂量LM49治疗的CD8 +数量增加。T细胞,与模型组相比。但是,LM49处理不影响血液学参数。我们的结果表明,通过调节免疫应答和抑制炎症介质,可以在APN动物模型中达到LM49的治疗效果,这表明它可以作为APN候选治疗药物。

更新日期:2018-07-11
down
wechat
bug