Objective To investigate suitable methods and efficacy for establishing a melasma animal model under natural high-altitude conditions (Lhasa City, 3650 m) using three approaches: the commonly used progesterone injection plus UV lamp irradiation (Model Ⅰ), and our research group's novel methods of progesterone injection plus natural light irradiation (Model Ⅱ) and natural light irradiation alone (Model Ⅲ). The goal is to provide experimental technical support for subsequent basic research.

Methods Twenty female SPF Kunming mice, aged 6-8 weeks and weighing 18-22 g, were selected in the plateau environment. The mice were randomly divided into four groups: progesterone injection plus UV lamp irradiation (Model Ⅰ), progesterone injection plus natural light irradiation (Model Ⅱ), natural light irradiation alone (Model Ⅲ), and a control group (Control), with five mice per group. The apparent status of mice in each group was observed. From days 29 to 40 after modeling, skin physiological parameters of all mice were measured every 2 days, including erythema index (E), melanin (M), skin type angle (ITA), skin lightness (L), redness (a), yellowness (b), and stratum corneum moisture content (CM). After 40 days of modeling, the following biochemical indicators were measured in serum, liver tissue homogenate (LTH), and skin tissue homogenate (STH) from each group: malondialdehyde (MDA), superoxide dismutase (SOD), tyrosinase (TYR), and other biochemical indicators. Correlation analysis was performed between skin physiological parameters and biochemical indicators (based on Model group Ⅰ data).

Results Compared with the Control group, the skin irradiation sites in the three Model groups showed dryness and marked hyperpigmentation. Mice in the Model groups also showed blunted responses, wet bedding, increased food intake, and increased urination, while the Control group showed no skin lesions. Skin physiological parameter results indicated that CM values in Model groups Ⅰ, Ⅱ, and Ⅲ were lower than those in the Control group (P < 0.05); ITA values in Model groups Ⅰ and Ⅲ were lower than in the Control group (P < 0.05); E and a values in all three Model groups were higher than in the Control group (P < 0.05); L values in Model group Ⅱ were lower than in the Control group (P < 0.05); and b values in Model groups Ⅰ and Ⅲ were higher than in the Control group (P<0.05). Biochemical indicators showed that, compared with the Control group, Model group Ⅰ had increased MDA_serum levels (P < 0.001), while Model group Ⅲ had elevated MDA_STH levels (P < 0.05). Additionally, Model group Ⅰ had lower SOD_LTH and SOD_STH activities than Model Ⅱ (P < 0.05). Correlation analysis indicated that MDA_LTH was positively correlated with E value (r = 0.72), while MDA_LTH and MDA_STH levels were negatively correlated with L value (r = －0.63, －0.72). Additionally, SOD_serum activity was positively correlated with ITA (r = 0.59).

Conclusion Model Ⅰ demonstrated superior modeling efficacy, while Models Ⅱ and Ⅲ remained incompletely stabilized.