Application of sigma-1 receptor entrapped exosome in preparation of antidepressant drugs
An exosome, anti-depressant technology, applied in the field of biomedicine
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Embodiment 1
[0040] Example 1 Preparation of exosomes loaded with sigma-1 receptor
[0041] 1. Experimental animals Male C57 mice were purchased from Shanghai Slack Experimental Animal Center, weighing 22-28 g; 4 mice per cage, free to eat and drink, room temperature 22±1°C, 12 hours of light / 12 hours of darkness per day , turn on the light at 7:00 in the morning, and acclimate to the environment for one week before the start of the experiment.
[0042] 2. Establishment of lipopolysaccharide (LPS)-induced depression model
[0043] LPS was purchased from Sigma Reagent Company, USA. According to the body weight of the mice, 0.83 mg / kg LPS was administered intraperitoneally. Behavioral and biochemical indicators were tested 24 hours after the injection of LPS to ensure the success of the modeling. .
[0044] 3. Depression model caused by chronic restraint stress
[0045] Place the mouse in a 50 ml transparent centrifuge tube, pierce a small hole for ventilation at the front end, and use ...
Embodiment 2
[0058] Example 2 Exosomes carrying sigma-1 receptors produce antidepressant effects
[0059] 1. See Example 1 for the method of making experimental animals and depression models
[0060] 2. Administration method
[0061] In this embodiment, preferably, a 0.4 mg / ml exosome physiological saline injection containing sigma-1 receptors is selected. The administration method is tail vein injection administration, and the administration volume is 0.1 ml / animal. The drug was administered when LPS was injected to start modeling, and the pharmacodynamic evaluation was performed 24 hours later.
[0062] 3. Forced swimming test
[0063] Take a 3000 mL beaker, inject 2000 mL of water and control the water temperature at 25±2°C, and put the mice into it. A video camera was used to record for 6 minutes, and the sum of the time that the mice remained immobile within 4 minutes after analysis.
[0064] 4. Tail suspension experiment
[0065] The tail of the mouse is fixed so that it hangs ...
Embodiment 3
[0080] Example 3 Exosomes loaded with sigma-1 receptors have rapid antidepressant characteristics, and the onset time is better than that of the existing antidepressant fluvoxamine
[0081] In this example, a depression model induced by chronic restraint stress was selected to evaluate the onset time of the antidepressant effect of exosomes loaded with sigma-1 receptors. A 0.4 mg / ml normal saline injection of exosomes loaded with sigma-1 receptors was selected. The administration method is tail vein injection administration, the administration volume is 0.1 ml / animal, and the administration is continued for 3 days. At the same time, the tail vein injection of fluvoxamine (a selective 5-HT reuptake inhibitor and sigma-1 receptor agonist) was used as a control at a dose of 10 mg / kg for 3 consecutive days.
[0082] The results showed that exosomes loaded with sigma-1 receptors could effectively reduce the forced swimming test ( Figure 6 A) and tail suspension experiments ( F...
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Abstract
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