Effects of Compound Gaoziban Tablet on NLRP3 inflammasome in hippocampus of depressed rats
OBJECTIVE To explore the alleviating effect of Compound Gaoziban Tablets(CGZBT)on depressive rats and examine the potential effects of NLRP3 inflammasome in hippocampus.METHODS After 1-week adaptive feeding,72 Sprague-Dawley(SD)rats were randomized into 6 groups of control,CUMS,CGZBT-L(0.4 g·kg-1),CGZBT-M(0.8 g·kg-1),CGZBT-H(1.6 g·kg-1)and fluoxetine based upon 0 weeks sugar-water preference(n=12 each).A depression model of chronic unpredictable mild stress(CUMS)was established after 6-week modeling.Appropriate pharmacological interventions were administered for 2 weeks starting from Week 5.Sugar preference,open field and forced swimming tests were conducted on the last day.Hippocampal and serum samples were collected after anesthesia.Hematoxylin-easin staining detected the changes of neurons in the CA1 of hippocampal tissue.The expression level of tumor necrosis factor-α(TNF-α)and interleukin-β(IL-1 β)in serum were detected by enzyme-linked inmunosorbent assacy.The expression levels of nod-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),cysteinyl aspartate specific proteinase-1(caspase-1),inter leukin-1β precursor(pro-IL-1β),IL-1 β and interleukin-18(IL-18)in hippocampus were detected by Western blot.RESULTS As compared with CUMS group,total distance in open field spiked markedly(P＜0.01)and immobile time of forced swimming declined(P＜0.01 or P＜0.05)in each dose group of CGZBT;sugar preference rate rose obviously in CGZBT-M and CGZBT-H groups(P＜0.01).CGZBT alleviated the injury of neuronal cells in CA1 region of hippocampus and lowered the serum levels of TNF-α and IL-1β(P＜0.01 or P＜0.05).As compared with CUMS group,protein expressions of ASC,caspase-1 and IL-1β were markedly down-regulated in hippocampus of rats in each dose group of CGZBT(P＜0.01 or P＜0.05);and protein expressions of NLRP3 and IL-18 were significantly down-regulated in hippocampus of rats in CGZBT-M and CGZBT-H groups(P＜0.01 or P＜0.05).CONCLUSION CGZBT alleviates depressive symptoms and down-regulates the expression of NLRP3 inflammasome in hippocampus of depressive rats.
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