Objective: To investigate the protective effect of carvacrol on astrocytes injury in spontaneous type 2 diabetic db/db mice. Methods: Twenty eight-week-old male db/db mice were randomly divided into model group and carvacrol group

and 10 db/m mice were randomized to the control group. The carvacrol group mice were given 20 mg/kg intragastric administration of carvacrol

and the control group and the model group were respectively given the same amount of intragastric administration of saline

once a day

for 6 weeks. The morphological changes of astrocytes in CA1 area of hippocampus in different groups were observed by labeling glial fibrillary acidic protein (GFAP) through immunohistochemistry. The number of expressed positive cells of lipocalin 2 (LCN2) and aquaporin 4 (AQP4) in CA1 region of control group

model group

and carvarol group were determined by immunohistochemistry. TUNEL was used to detect the relationship among LCN2

AQP4 and astrocyte apoptosis in CA1 region. RT-PCR and Western blot were used to detect the expression of LCN2

AQP4

nuclear factor kappa B (NF-κB) and neutrophilic alkaline phosphatase-3 (NALP3) in CA1 area of hippocampus in control group

model group and carvacrol group. Results: The expression levels of glucose (GLU)

high density lipoprotein (HDL)

triglyceride (TG) and total cholesterol (TC) in the model group were significantly higher than those in the control group

while the expression levels of GLU

HDL

TG and TC in the carvacrol group were significantly lower than those in the model group (all P<0.05). Immunohistochemistry showed that the number of GFAP labeled astrocytes in the model group increased and the number of branches increased

while the carvacrol group could improve the morphology of astrocytes and reduce the number (all P<0.01). Immunohistochemistry also showed that the number of positive cells of LCN2

NF-κB and NALP3 in the model group increased

while the number of positive cells of AQP4 decreased. However

in the carvacrol group

the number of positive cells of AQP4 increased

and the number of positive cells of LCN2

NF-κB and NALP3 decreased (all P<0.01). TUNEL staining showed that LCN2 and apoptotic cells increased

while AQP4 decreased significantly in the model group

while the number of apoptotic cells and LCN2 positive cells and AQP4 positive cells increased in the carvacrol group compared with the model group (all P<0.01). The results of RT-PCR and Western blot showed that the expression levels of LCN2

NALP3 and NF-κB in hippocampus of carvacrol group were decreased

and the expression level of AQP4 was increased compared with those of model group (all P<0.01). Conclusion: Carvacrol has protective effect on astrocytes injury in spontaneous type 2 diabetic mice

and its mechanism may be related to the decrease of LCN2

NF-κB and NALP3

and the increase of AQP4 expression level.