BALB/c mice were randomly divided into a control group, a model group, an
aspirin group, a low-dose
ginsenoside Rb1 group (50 mg/kg), and a high-dose
ginsenoside Rb1 group (100 mg/kg), with 12 mice in each group. All mice except those in the control group were given intermittent
intraperitoneal injection of 10%
bovine serum albumin to establish a mouse model of KD. The mice in the
aspirin group, the low-dose
ginsenoside Rb1 group, and the high-dose
ginsenoside Rb1 group were given the corresponding
drug by gavage for 20 days after modeling.
Hematoxylin and
eosin staining was used to observe the pathological changes of coronary artery tissue. ELISA was used to measure the levels of the inflammatory
cytokines tumor necrosis factor-α (TNF-α),
interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum and coronary artery tissue. Western blot was used to measure the relative expression levels of
proteins involved in the regulation of the AMPK/mTOR autophagy signaling pathway and the PI3K/Akt oxidative stress signaling pathway in coronary artery tissue.
RESULTS: The observation of pathological sections showed that compared with the model group, the high-dose
ginsenoside Rb1 group had significant improvement in the symptoms of vascular wall thickening, intimal
edema, fiber
rupture, and inflammatory infiltration of endothelial cells. Compared with the control group, the model and low-dose
ginsenoside Rb1 groups had significant increases in the levels of TNF-α,
IL-6, and IL-1β in serum and coronary artery tissue (P<0.05); the model group had significant increases in the expression levels of P-AMPK/AMPK, P-mTOR/mTOR, and P-P70S6/P70S6 in coronary artery tissue (P<0.05) and significant reductions in the expression levels of P-PI3K/PI3K, P-AKT/AKT, and P-GSK-3β/GSK-3β in coronary artery tissue (P<0.05). Compared with the model group, the
aspirin group and the high-dose
ginsenoside Rb1 group had significant reductions in the levels of TNF-α,
IL-6, and IL-1β (P<0.05); the low- and high-dose
ginsenoside Rb1 groups had significant reductions in the expression levels of P-AMPK/AMPK, P-mTOR/mTOR, and P-P70S6/P70S6 (P<0.05) in a dose-dependent manner between the two groups (P<0.05); the low-dose
ginsenoside Rb1 group had no significant change in the expression level of P-PI3K/PI3K (P>0.05) and had significant increases in the expression levels of P-AKT/AKT and P-GSK-3β/GSK-3β (P<0.05), while the high-dose
ginsenoside Rb1 group had significant increases in the relative
protein expression levels of the above three
proteins (P<0.05). Compared with the low-dose
ginsenoside Rb1 group, the
aspirin group and the high-dose
ginsenoside Rb1 group had significant reductions in the levels of TNF-α,
IL-6, and IL-1β (P<0.05); the high-dose
ginsenoside Rb1 group had significant increases in the expression levels of P-PI3K/PI3K and P-AKT/AKT (P<0.05).
CONCLUSIONS:
Ginsenoside Rb1 can effectively alleviate CAL in a mouse model of KD in a dose-dependent manner, possibly by regulating the AMPK/mTOR/P70S6 autophagy signaling pathway to inhibit CAL
inflammation and regulating the PI3K/AKT/GSK-3β oxidative stress signaling pathway to exert a
biological activity of protection against coronary artery endothelial cell injury.