Platelet Hyperactivation Plays a Critical Role in Exacerbating Skin Lesions in Rats with Psoriasis and Blood Stasis...

Psoriasis with blood stasis syndrome (BSS) demonstrates aggravated skin lesions compared to psoriasis alone; however, the underlying mechanism remains unclear. This study aims to elucidate the pathological mechanisms of skin lesion exacerbation in psoriasis from the perspective of platelet activation.

A psoriasis rat model was established by topical application of imiquimod (IMQ), while a psoriasis with BSS model was induced using ice-water baths and epinephrine injection. Skin lesions were assessed via hematoxylin and eosin (H&E) staining. Hemorheology was employed to evaluate BSS characteristics. Western blot (WB) was used to examine CD62P (P-selectin) and platelet-activating factor receptor (PAFR) expression to assess platelet activation. The platelet aggregation inhibitor clopidogrel was administered via oral gavage. The psoriasis area and severity index (PASI) was applied to evaluate clopidogrel's therapeutic effect, and network pharmacology combined with quantitative reverse transcription PCR (RT-qPCR) was used to clarify its mechanism.

HE staining indicated more severe skin lesions in psoriasis with BSS rats than in psoriasis rats (P<0.01). Hemorheological analysis revealed increased blood viscosity and microvascular proliferation in the psoriasis rats with BSS. WB showed significantly elevated expression of CD62P and PAFR in psoriasis with BSS rats (P<0.05). Clopidogrel reduced epidermal thickening, as assessed by the PASI score. Network pharmacology and RT-qPCR identified P2RY12 and GPIIb/IIIa as key targets through which clopidogrel ameliorates skin lesions in psoriasis with BSS.

Psoriasis with BSS rats exhibit more severe skin lesions than psoriasis rats, associated with enhanced platelet activation. Clopidogrel improved blood stasis and skin inflammation, confirming that platelet activation contributes critically to skin lesion worsening.