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Application of a drug instead of antibiotics--melatonin against meningitis Escherichia coli pathogenic infection in children

A technology to replace antibiotics and Escherichia coli, applied in the direction of resistance to vector-borne diseases, antibacterial drugs, drug combinations, etc. Reduce expression and invasion of inflammatory cells, reduce mortality and tissue damage, and reduce the effect of inflammatory responses

Active Publication Date: 2022-06-24
YANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are mainly the following problems in the prevention of meningitis: the blood-brain barrier of newborns is not fully developed, so pathogenic bacteria will invade the brain, and it is necessary to find drugs that can promote the development of the blood-brain barrier and have a preventive effect; a large number or excessive use of antibiotics will It leads to the confusion of the intestinal flora of the body, the decline of the body's metabolism and immunity, and the emergence of bacterial drug resistance; therefore, it is very important to find more effective drugs to replace antibiotics
However, the protective effect of melatonin instead of antibiotics in preventing the onset of meningitis in mice infected with APEC XM-TW has not been reported, and the prevention of meningitis in mice by regulating intestinal microbes has not been reported, so this study is innovative Innovative, advanced and applicable, providing new ideas and technical means for the prevention of meningitis

Method used

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  • Application of a drug instead of antibiotics--melatonin against meningitis Escherichia coli pathogenic infection in children
  • Application of a drug instead of antibiotics--melatonin against meningitis Escherichia coli pathogenic infection in children
  • Application of a drug instead of antibiotics--melatonin against meningitis Escherichia coli pathogenic infection in children

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] 1. Main drugs and reagents

[0045] Melatonin (MT), purchased from Sigma, USA; formalin, PBS, DAB reagent, hematoxylin, eosin, distilled water. Tryptone (Tryptone) and yeast extract (Yeast extract) were purchased from Oxoid Company; sodium chloride (NaCl), hydrogen citrate diamine (C 6 H 14 N 2 O 7 ), sodium acetate (CH 3 COONa), dipotassium hydrogen phosphate (K 2 HPO 4 ), magnesium sulfate (MgSO 4 ), manganese sulfate (MnSO 4 ) and other analytical reagents were purchased from Sinopharm Group Chemical Reagent Co., Ltd.; MacConkey agar was purchased from Haibo Company; Streptomycin, Ampicillin, Gentamicin, and Vancomycin were purchased from Solebao Company; EVANS BLUE dyeing agent , glucose (Glucose) were purchased from Sigma company; Faststart Universal SYBR GREEN Master (ROX) fluorescence quantitative kit was purchased from Roche company; paraffin, slides, coverslips, saline, 1mL syringes were purchased from Bibang company; All reagents were domestic analyti...

Embodiment 2

[0082] (1) Preparation of APEC TW-XM strain

[0083] First, recover the bacteria from the seed storage tube, streak the four areas on the LB solid plate, and cultivate overnight in a 37°C incubator. The next day, pick a single colony and cultivate it in liquid LB medium for 16 hours. The ratio of bacterial liquid was transferred to liquid LB medium and cultivated to OD 600 When = 1, collect the bacterial liquid, wash the bacterial suspension with PBS twice, and resuspend it with normal saline, and dilute it to cfu = 10. 7 , for mouse infection.

[0084] (2) Experiment of melatonin preventing the onset of meningitis in mice

[0085] Mice were randomly divided into four groups, 6 mice in (NS) group, 6 mice in melatonin (MT) group, and 26 mice in APEC TW-XM (A) group (10 mice - bacterial count, 6 mice - pathological section, 10 mice were used for Statistical survival rate), APEC TW-XM+melatonin (A+MT) group of 26 (10-bacterial count, 6-pathological section, 10 for statistical ...

Embodiment 3

[0104] (1) Preparation of APEC TW-XM strain

[0105] Same as Example 2.

[0106] (2) Experiment of melatonin regulating intestinal flora to prevent the onset of meningitis

[0107] Mice were randomly divided into four groups, APEC TW-XM group: intraperitoneal injection of 100 μl of normal saline every day; sterile water was changed every day; A+MT group: 100 μl of 30 mg / kg MT was injected intraperitoneally every day; sterile water was replaced every day; A+antibiotic group: intraperitoneal injection of 100 μl of normal saline every day; change of sterile water containing antibiotics every day; A+antibiotics + MT: intraperitoneal injection of 100 μl of 30 mg / kg MT every day; change of sterile water containing antibiotics every day; 8 days for challenge (cfu=10 7 ) to collect the sample.

[0108] (3) Sample collection

[0109] Penetration test (EB staining): Same as Example 1.

[0110] Detection of inflammatory factors: the same as Example 1.

[0111] Production of patholo...

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Abstract

The invention provides an application of melatonin, a medicine replacing antibiotics, to prevent Escherichia coli pathogenic infection of children with meningitis. Meningitis-type Escherichia coli was isolated and identified from the cerebrospinal fluid of muscovy ducks. This strain was used to construct a 3-week-old ICR mouse meningitis model for the first time, and the neurological symptom score, mortality difference statistics, blood-brain barrier damage degree, and meningitis-related inflammatory factors were respectively evaluated. Expression and other aspects to evaluate the successful construction of the mouse meningitis model. Taking antibiotics as a reference, the mice were treated with melatonin and four kinds of combined antibiotics, and the onset of meningitis mice was detected one week later. The results showed that both melatonin and combined antibiotics could reduce the neurological symptoms of meningitis mice. Improve the survival rate of meningitis mice, melatonin promotes the integrity of the blood-brain barrier, reduces the invasion of inflammatory cells into the central nervous system, prevents the onset of meningitis in mice through the brain-gut axis, and provides a new way to prevent neonatal meningitis. Antibiotic alternatives and treatment strategies.

Description

technical field [0001] The invention relates to the application of melatonin (melatonin), a medicine for replacing antibiotics, in resisting the pathogenic infection of children with meningitis Escherichia coli. The present invention further provides a medicine for preventing the onset of meningitis as a substitute for antibiotics and its application characteristics, and is expected to provide a new strategy for preventing the onset of meningitis. Background technique [0002] Since the first report of bacterial meningitis (BM) by Vieusseux in 1806, the disease has been regarded as an important fatal disease, and it is a central nervous system infection of human and animal clinical concern. There are many pathogens that cause bacterial meningitis, and the mortality rate of neonatal meningitis caused by Escherichia coli ranks among the highest in the world. Meningogenic Escherichia coli mainly include Neonatal Meningitis Escherichia coli (NMEC) and Avian meningitis Escherich...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4045A61P25/00A61P31/04A01K67/02
CPCA61K31/4045A61P25/00A61P31/04A01K67/02A01K2227/105A01K2267/03Y02A50/30
Inventor 武琥琮刘家奇朱国强张东夏芃芃任文凯
Owner YANGZHOU UNIV
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