ABSTRACT
Objective:
To investigate the antagonistic and
therapeutic effects of
Ginkgo biloba on
arsenic-induced
lung injury in
rats and its mechanism.
Methods:
A total of 42 healthy clean grade
Wistar rats, half
male and half
female, weighing 120 - 130 g, were randomly divided into 7 groups with 6
rats in each group. Two intervention models of
Ginkgo biloba antagonism and
treatment were established, respectively. The specific
treatments were as follows (1)
Experimental study on the antagonism of
Ginkgo biloba (4 groups) the control A group was given
deionized water; the
Ginkgo biloba control (GBE) group was given
Ginkgo biloba solution (50 mg·kg -1·bw); the
arsenic-treated (As) group was given
sodium arsenite
solution (10 mg·kg -1·bw); the
Ginkgo biloba antagonistic (As + GBE) group was treated with
sodium arsenite
solution (10 mg·kg -1·bw) and
Ginkgo biloba solution (50 mg·kg -1·bw), and the above
administration was by gavage for 6 days/week, for 4 months. (2)
Experimental study on the
treatment of
Ginkgo biloba (3 groups) the control B group was given
deionized water for 5.5 months; in the arsenism natural recovery (recovery) group,
sodium arsenite
solution (10 mg·kg -1·bw) was administered by gavage for 4.0 months and
deionized water for 1.5 months; the
Ginkgo biloba treatment (
treatment) group was given
sodium arsenite
solution (10 mg·kg -1·bw) by gavage for 4.0 months and
Ginkgo biloba solution (50 mg·kg -1·bw) for 1.5 months, and the above
administration was for 6 days/week. Masson
staining was used to evaluate
collagen fiber deposition in
lung tissue.
Western blotting was used to detect the expression level of related
proteins in
lung tissue homogenates, including inflammatory
cytokines matrix metalloproteinase-9 (
MMP-9),
interleukin (IL)-1β,
IL-18; high mobility group box 1 (
HMGB1) and receptor for advanced
glycation end-products (
RAGE) of the
HMGB1/
RAGE pathway;
phosphatidylinositol-4, 5-bisphosphate 3-
kinase (PI3K),
protein kinase B (AKT), phosphorylated AKT (p-AKT) of the PI3K/AKT pathway;
transforming growth factor (TGF)-β1, SMAD2, p-SMAD2, SMAD3, p-SMAD3 and SMAD4 of the TGF-β1/SMAD pathway.
Results:
(1) Antagonistic effect of
Ginkgo biloba compared with the control A group, there was no significant change in
protein expression and
collagen fiber deposition in the
lung tissue of GBE group ( P > 0.05); the levels of
MMP-9,
IL-1β and
IL-18 protein expression and
collagen fiber deposition in the
lung tissue of As group were significantly increased ( P < 0.05); and the levels of
HMGB1,
RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, p-SMAD3 and
SMAD4 protein expression were significantly increased ( P < 0.05). Compared with As group, the levels of
MMP-9,
IL-1β and
IL-18 protein expression and
collagen fiber deposition were significantly decreased in As + GBE group ( P < 0.05); and levels of
HMGB1,
RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, and p-
SMAD3 protein expression were significantly decreased ( P < 0.05). (2)
Therapeutic effect of
Ginkgo biloba compared with control B group, the levels of
MMP-9,
IL-1β,
IL-18 protein expression and
collagen fiber deposition were significantly increased in recovery group ( P < 0.05); and the levels of
HMGB1,
RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, p-SMAD3 and
SMAD4 protein expression were significantly increased ( P < 0.05). Compared with recovery group, the levels of
MMP-9,
IL-1β,
IL-18,
HMGB1,
RAGE, PI3K and p-AKT
protein expression were significantly decreased in
treatment group ( P < 0.05); and there was no significant change in
collagen fiber deposition and TGF-β1, p-SMAD2, p-SMAD3 and
SMAD4 protein expression levels in
lung tissue ( P > 0.05). In both experiments, there was no significant difference in the
protein expression levels of AKT, SMAD2 and SMAD3 between the groups ( P > 0.05).
Conclusion:
Ginkgo biloba intervention has ameliorated inflammatory
injury and
collagen fiber deposition in
lung tissue of
arsenic-treated
rats possibly by inhibiting the expression levels of
HMGB1/
RAGE pathway-related
proteins.