Objective To explore the effect of shikonin (SHI) on the treatment of granuloma lobular mastitis in model rats by regulating nuclear factor-erythroid 2 related factor 2/heme oxygenase (Nrf2/HO-1) signaling pathway and its mechanism. Methods The rat model of granuloma lobular mastitis (GLM) was established. Rats were grouped into a control group, a model group (GLM group), a low-dose shikonin group (SHI-L group, 17.5 mg?kg-1·d-1 SHI), a medium-dose shikonin group (SHI-M group, 35 mg?kg-1·d-1 SHI), a high-dose shikonin group (SHI-H group, 70 mg?kg-1·d-1 SHI), and a high-dose shikonin+Nrf2 inhibitor ML385 group (SHI-H+ML385 group, 70 mg?kg-1·d-1 SHI+14 mg?kg-1·d-1 ML385). HE staining was applied to observe the pathological changes of breast tissue. ELISA was applied to detect the levels of IL-1β, TNF-α, IL-8, T-AOC, SOD, GSH, MPO, NAGas, and ROS in breast tissue. Immunofluorescence was applied to detect NLRP3 expression. Western blotting was used to detect the expression of Nrf2 and HO-1 proteins. Results Compared with the control group, the mammary lobule of rats in GLM group was completely destroyed, large nodular chronic granuloma inflammatory lesions were generated, the boundary of the mammary lobule tissue was unclear, vacuoles appeared in the glandular lobe, and accompanied by infiltration of a large number of lymphocytes and neutrophils. The levels of IL-8, IL-1β, TNF-α, ROS, MPO and NAGas, and the positive expression rate of NLRP3 were obviously increased (P<0.05), the levels of T-AOC, SOD, and GSH, and the expression of Nrf2 and HO-1 proteins were obviously reduced (P<0.05). Compared with the GLM group, the breast tissue lesions in the SHI-L, SHI-M, and SHI-H groups gradually decreased, the levels of IL-8, IL-1β, TNF-α, ROS, MPO and NAGas, the positive expression rate of NLRP3 were sequentially reduced (P<0.05), the levels of T-AOC, SOD, and GSH, and the expression of Nrf2 and HO-1 proteins were sequentially increased (P<0.05). Compared with the SHI-H group, the SHI-H+ML385 group had more severe breast tissue lesions, the levels of IL-8, IL-1β, TNF-α, ROS, MPO and NAGas, and the positive expression rate of NLRP3 were obviously increased (P<0.05), the levels of T-AOC, SOD, and GSH, and the expression of Nrf2 and HO-1 proteins were obviously reduced (P<0.05). Conclusions Shikonin can improve granulomatous lobular mastitis in rats by exerting anti-inflammatory and antioxidant effects, which may be related to the activation of Nrf2 signaling pathway and upregulation of HO-1 expression.
Key words
Shikonin; /
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Nuclear factor-erythroid 2 related factor 2/heme oxygenase signaling pathway /
Granuloma lobular mastitis
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