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MB Sample ID: SA209166

Local Sample ID:2020-08-17_Zang-43_Box2Redo-9_NEG
Subject ID:SU002264
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Age Or Age Range:10-week and 24-month
Gender:Male

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Treatment:

Treatment ID:TR002276
Treatment Summary:Endotoxemia was induced in young (10-week) and aged (24-week) male mice by lipopolysaccharide (LPS). Based on published results as well as observations in our laboratory, male and female mice showed significantly different susceptibility to systemic symptoms in sepsis models. Thus, male but not female mice were chosen for the experiments presented in this report. LPS was administered intraperitoneally (i.p.), and mice were weighed individually to determine the exact amount of LPS (MilliporeSigma, Burlington, MA; catalog number L3012) required to achieve the required doses. Sterile endotoxin-free PBS was used as a vehicle control in sham groups. Consistent with literature and as expected, we observed that older mice were more susceptible to the toxic effects induced by LPS. 24-month-old (aged) mice showed impaired cardiac function but were able to survive when receiving LPS challenged at 1mg/kg. However, greater fatality was observed when LPS dose was increased to 3 mg/kg. In 10-week-old (young adult) mice, 3 mg/kg LPS triggered heart dysfunction without impact on survival, whereases at 10 mg/kg, we observed significant LPS-induced fatality in the group. Due to the different sensitivities to LPS between the aged and young adult mice, we were not able to choose a universal dose of LPS to induce cardiac dysfunction and to perform follow up analysis in both groups. Therefore, we used the physiological function of the heart as a base for comparison in the studies performed in this report. Our previous research provided evidence that stimulating beclin-1 dependent autophagy improves cardiac performance during endotoxemia in young adult mice, and thus Beclin-1-activating peptide (TB peptide) holds a promising therapeutic potential for sepsis. In this report, we examined whether TB-peptide exerts a similar protective effect on aged animals under the same condition. In our experimental setting, sham or LPS challenge was administered to groups of 24-month-old and 10-week-old mice followed by treatment with TB-peptide, administered i.p. at a dose of 16 mg/kg in 100μl of PBS 30 minutes post LPS-challenge. Heart tissue was collected 18 hours post LPS challenge.
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