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Development of an Experimental Model of Vasculitis Using Ovalbumin Lipopolysaccharide in Rats

  • Vandana R. Thakur,
  • Anita A. Mehta

摘要

Vasculitis is considered a veiled threat for several pathologic conditions, and consequently, there is a need to develop a distinct animal model for drug testing. An adjunct use of antigens, ovalbumin (OVA), and lipopolysaccharide (LPS) has been reported in exaggerating inflammation. However, the effects of OVA and LPS individually or in combination have not yet been established in inducing vasculitis. The present study examined effects of OVA and LPS on vasculitis induction in rats. Rats treated with OVA (5 mg/kg, i.p.) and LPS (1 mg/kg, i.p.) showed a significant increase in circulating inflammatory cells, erythrocyte sedimentation rate, inflammatory cytokines (IL-1β, IL-6, and TNF-α), c-reactive protein, anti-neutrophil cytoplasmic antibodies (anti-myeloperoxidase (MPO), anti-proteinase-3 (PR3)), liver function enzymes (AST, ALT), and kidney damage markers (BUN, Creatinine) in the serum. Matrix metalloproteinase (MMP)-9 levels were significantly increased in the temporal, carotid, aortic, iliac, mesentery, and coronary arteries. In addition, the diseased group developed hematuria and proteinuria, which was incomparable to the normal group. Histopathology further revealed significant neutrophil infiltration accompanied by fibrinolytic necrosis, indicating vascular injury and hyperplasia, leading to extracellular matrix degradation. In conclusion, the combination of ovalbumin and lipopolysaccharide has developed vasculitis-like conditions, which suggest OVA-LPS can be a new experimental model for vasculitis and be considered in future therapeutic studies.