3.5 Koumine inhibits DNP-induced BLA astrocyte activation and
ameliorates the inflammatory response
Given the role of BLA astrocytes in the development of pain
hypersensitivity, we sought to examine whether the observed
anti-allodynic effects of KM in the diabetic rats could occur by
inhibiting the activation of BLA astrocytes. Immunofluorescence staining
of the BLA showed that there was an increase proliferation and
hypertrophy of astrocytes in the BLA, indicating that the activation of
astrocytes was evidently increased in the DNP rats; however, treatment
with KM (0.28, 1.4, and 7.0 mg/kg) attenuated the upregulation of GFAP
in the diabetic rats (Fig. 6A-6C).
A dramatic increase in inflammatory cytokine levels is one of the major
features of astroglial activation. Previous studies have reported that
the release of inflammatory cytokines from active astrocytes is the
primary cause of DNP (Ji et al., 2014). We examined the expression of
proinflammatory cytokines in BLA tissue to investigate whether KM
affected the inflammatory response caused by BLA astrocyte activation.
ELISA results showed that TNF-α, IL-1β, CXCL1 and MCP-1 levels were
markedly increased in the BLA of the DNP rats compared to those in the
BLA of the control rats; however, this upregulation was reversed by KM
(Fig. 7A-7D). Taken together, these results suggested that KM
substantially inhibited DNP-induced BLA astrocyte activation and
suppressed the astrocyte activation-induced inflammatory response.