[Animal modeling] - Optimization of interstitial cystitis model in rats induced by intraperitoneal injection of cyclophosphamide

  Objective To explore the ideal dose of cyclophosphamide for establishing interstitial cystitis model in rats.

  Methods The rats were randomly divided into seven groups, and the interstitial cystitis models were established by intraperitoneal injection of normal saline as control or 50 mg/kg, 100 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg and 300 mg/kg cyclophosphamide. HE staining and Real time PCR were used to evaluate the inflammatory effect of different doses of cyclophosphamide on bladder tissue at the histological and molecular levels. Urinary dynamics, behavior scale and Von Frey test were used to evaluate bladder function and sensation, and comprehensively evaluate the modeling of rats in each group.

  Results There was no significant difference in bladder inflammation index and spontaneous hyperalgesia score between the 50mg/kg group and the control group. The inflammatory index of bladder in the 100 mg/kg group was significantly higher than that in the control group (P<0.05), but there was no significant difference between the spontaneous hyperalgesia and the control group; The bladder inflammation indexes of 150 mg/kg and 200 mg/kg rats were significantly higher than those of the control group (P<0.05), and spontaneous hyperalgesia occurred (P<0.05). The rats in the 200 mg/kg group died within 48 hours after CYP injection; Although the indexes of bladder inflammation and spontaneous pain threshold of rats in 250 mg/kg and 300 mg/kg groups were significantly higher than those in the control group (P<0.05), the contractility of bladder was impaired (P<0.05), and rats died within 48 hours after cyclophosphamide injection.

  Conclusion The intraperitoneal injection of cyclophosphamide (150 mg/kg) is an ideal method to establish the model of interstitial cystitis in rats, which can simultaneously simulate the two characteristics of interstitial cystitis: bladder inflammation and spontaneous pain, and take into account the modeling efficiency and rat survival rate.