[Animal modeling] Preventive and therapeutic effects of diaminazine in rats with pulmonary hypertension

  Objective: To investigate the preventive and therapeutic effects of diaminazine (DIZE) on pulmonary hypertension (PAH) in rats.

  Methods: PAH rat model was established by left lobectomy combined with subcutaneous injection of monocrotaline (MCT) into abdominal wall. 100 adult male Wistar rats were randomly divided into blank control group (Group A), DIZE control group (Group B), PAH model group (Group C), DIZE treated PAH model group (Group D) and (DIZE+C-16) treated PAH model group (Group E), Active fluorescence resonance energy transfer (FRET) and enzyme linked immunosorbent assay (ELISA) were used to measure the levels of angiotensin converting enzyme 2 (ACE2), serum IL-6 and IL-8, and the mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) were measured. The ratio of middle membrane thickness to pulmonary artery outer diameter (WT) and intimal hyperplasia score were calculated. Pulmonary vascular disease was analyzed by elastic fiber staining.

  Results: Comparison of RVHI, ACE2 enzyme activity, WT and intimal hyperplasia scores: Compared with group A, there were significant differences among group C, group D and group E (P<0.05); The difference between group D and group E was statistically significant (P<0.05). There were significant differences among the five groups in the overall analysis of each index (P<0.05).

  Conclusion: Diamidinazine can increase the activity of ACE2 enzyme, effectively reduce mPAP, RVHI and WT, reduce the hypertrophy of pulmonary artery middle membrane, and inhibit the proliferation of pulmonary arteriole intima. This study provides an experimental basis for the treatment of human PAH with amikacin.